Citation
Two-dimensional self-assembly of amphiphilic block copolymers at the air/water interface and nanoparticles for drug detoxification applications

Material Information

Title:
Two-dimensional self-assembly of amphiphilic block copolymers at the air/water interface and nanoparticles for drug detoxification applications
Creator:
Joncheray, Thomas Julien ( Dissertant )
Duran, Randolph ( Thesis advisor )
Wagener, Kenneth B. ( Reviewer )
Castellano, Ronald K. ( Reviewer )
Lyons, Thomas J. ( Reviewer )
Sigmund, Wolfgang M. ( Reviewer )
Place of Publication:
Gainesville, Fla.
Publisher:
University of Florida
Publication Date:
Copyright Date:
2006
Language:
English
Physical Description:
184 p.

Subjects

Subjects / Keywords:
Block copolymers ( jstor )
Copolymers ( jstor )
Ferrocenes ( jstor )
Isotherms ( jstor )
Micelles ( jstor )
Molecules ( jstor )
Money market accounts ( jstor )
Nanoparticles ( jstor )
Pressure ( jstor )
Surface water ( jstor )
Chemistry thesis, Ph.D ( local )
Dissertations, Academic -- UF -- Chemistry ( local )

Notes

Abstract:
The two-dimensional self-assembly at the air/water (A/W) interface of various block copolymers (dendrimer-like polystyrene-b-poly(tert-butylacrylate) (PS-b-PtBA) and polystyrene-b-poly(acrylic acid) (PS-b-PAA), linear and five-arm star poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-b-PCL), and three-arm star triethoxysilane-functionalized polybutadiene-b-poly(ethylene oxide) (PB(Si(OEt)3)-b-PEO)) was investigated through surface pressure measurements (isotherms, isobars, isochores, and compression-expansion hysteresis experiments) and atomic force microscopy (AFM) imaging. The PS-b-PtBA and the PS-b-PAA samples formed well-defined circular surface micelles at low surface pressures with low aggregation numbers (~ 3-5) compared to linear analogues before collapse of the PtBA chains and aqueous dissolution of the PAA segments take place around 24 and 5 mN/m, respectively. The linear PEO-b-PCL samples exhibited three phase transitions at 6.5, 10.5, and 13.5 mN/m corresponding respectively to PEO aqueous dissolution, PEO brush formation, and PCL crystallization. The two PEO phase transitions were not observed for the star-shaped PEO-b-PCL samples because of the negligible surface activity of the star-shaped PEO core compared to its linear analogue. The PB(Si(OEt)3)-b-PEO sample was cross-linked at the A/W interface by self-condensation of the pendant triethoxysilane groups under acidic conditions, which resulted in the formation of a two-dimensional PB network containing PEO pores with controllable sizes. With a view toward drug detoxification therapy, the encapsulation abilities of oil core-silica shell nanocapsules and molecularly imprinted nanoparticles were also investigated by electrochemical (cyclic voltammetry) and optical (fluorescence and UV-vis spectroscopies) techniques. The core-shell nanocapsules were shown to efficiently remove large amounts of organic molecules present in aqueous solutions, with the silica shell acting analogously to a chromatographing layer. The molecularly imprinted nanoparticles were prepared by the non-covalent approach and by miniemulsion polymerization. Binding studies on the molecularly imprinted nanoparticles in aqueous solutions under physiological pH conditions indicated that, in the absence of specific imprinting, the uptake of toxic drugs was mainly driven by non-specific hydrophobic interactions. As demonstrated with the use of the antidepressant amitriptyline, in the presence of specific imprinting the uptake significantly increased as the amount of specific binding sites was increased.
Subject:
Afm, amitriptyline, binding, blodgett, bupivacaine, copolymer, crosslinking, detoxification, drug, encapsulation, hydrosilylation, imprinting, interface, isotherm, langmuir, microemulsion, miniemulsion, nanocapsule, nanoparticle, paa, pbut, pcl, peo, polymerization, ps, ptba, silica, triethoxysilane, uptake
General Note:
Title from title page of source document.
General Note:
Document formatted into pages; contains 184 pages.
General Note:
Includes vita.
Thesis:
Thesis (Ph.D.)--University of Florida, 2006.
Bibliography:
Includes bibliographical references.
General Note:
Text (Electronic thesis) in PDF format.

Record Information

Source Institution:
University of Florida
Holding Location:
University of Florida
Rights Management:
Copyright Joncheray, Thomas Julien. Permission granted to the University of Florida to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder.
Embargo Date:
3/1/2007
Resource Identifier:
434595882 ( OCLC )

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Full Text





TWO-DIMENSIONAL SELF-ASSEMBLY OF AMPHIPHILIC BLOCK COPOLYMERS AT
THE AIR/WATER INTERFACE AND NANOPARTICLES FOR DRUG DETOXIFICATION
APPLICATIONS






















By

THOMAS J. JONCHERAY


A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL
OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT
OF THE REQUIREMENTS FOR THE DEGREE OF
DOCTOR OF PHILOSOPHY

UNIVERSITY OF FLORIDA

2006
































Copyright 2006

by

Thomas J. Joncheray









ACKNOWLEDGMENTS

First and foremost, I would like to thank my parents, Dominique Joncheray and Catherine

Stona, my sister, Alice Joncheray, as well as the rest of my family, past and present, for being an

endless source of support in my education and life. In February 2001, I met Emilie Galand in

Bordeaux who came to the University of Florida with me where we spent together almost five

years of graduate school. I could not have achieved this seemingly insurmountable amount of

work without her. We supported each other through these challenging years, and helped each

other through the difficult times.

I would like to acknowledge my research director, Prof. Randolph S. Duran, for his help

and support over the years I spent under his supervision. His experienced advice has been an

integral part of my education and has given me a deeper understanding of what is needed to be

successful as a research chemist. I would like also to thank the other members of my Ph.D.

committee: Prof. Kenneth B. Wagener, Dr. Ronald K. Castellano, Dr. Thomas J. Lyons, and Dr.

Wolfgang M. Sigmund.

I am also very grateful to the many collaborators I have had the chance to interact with

over the years I spent in graduate school. I have had the pleasure of working with Prof. Audebert

from ENS Cachan on the nanocapsule project. He provided very interesting discussions and

ideas, and always made himself available when I needed his help. I also really appreciated the

collaboration on PEO-b-PCL block copolymers I had with Prof. Schubert and particularly with

Dr. Mike Meier from the Eindhoven University of Technology. It was a pleasure to have Mike

and Jutta staying for a few days at the University of Florida, and Emilie and I also enjoyed very

much the time spent in Eindhoven. I express my appreciation to Prof. Gnanou from the

Laboratoire de Chimie des Polymeres Organiques in Bordeaux, France, for his input in the PS-b-










PtBA, PS-b-PAA, and PB-b-PEO proj ects, and for helping me in j oining the graduate program of

the University of Florida.

At the University of Florida, special thanks go to the polymer floor and the Chemistry

Department staff, most notably Lorraine Williams, Sara Klossner, and Lori Clark for their

patience in answering my various questions. I want to show my gratitude to the three professors

of the Butler Polymer Laboratory, Prof. Duran, Prof. Wagener, and Prof. Reynolds, for putting a

lot of effort in providing the polymer floor members with a superior work environment to

conduct research in polymer chemistry. I want to thank all my co-workers from the Duran group

and from the George and Josephine Butler polymer floor. Special thanks need to go to Rachid

Matmour, who made the time spent in the lab really enjoyable. It was a pleasure working with

him, often in a hilarious atmosphere, on several challenging research projects. Other group

members to whom I owe extra thanks for their help along the way are Dr. Aleksa Jovanovic, Dr.

Jennifer Logan, Jorge Chavez, Sophie Bernard, Brian Dorvel, Rita El-Khouri, Kristina

Denoncourt, and Claire Mathieu.

Finally, I would like to thank all the friends I have had the chance to meet and interact with

inside or outside the Chemistry Department, especially Benoit Lauly, Christophe Grenier, Pierre

Beaujuge, and Changhwan Ko who made my days in Gainesville very enj oyable.











TABLE OF CONTENTS


page

ACKNOWLEDGMENTS .............. ...............3.....

LIST OF TABLES ............ ..... .__ ...............8...

LIST OF FIGURES .............. ...............9.....

AB S TRAC T ........._. ............ ..............._ 15...

CHAPTER

1 INTRODUCTION ................. ...............17.......... ......

1.1 Block Copolymers in the Bulk and in Solution ................. ...............17...........
1.2 Block Copolymers at the A/W Interface .............. ...............20....
1.3 Current Status of Drug Detoxification Therapy .............. ...............23....
1.4 Nanoparticle Technology............... .................2
1.5 Microemulsions and Sol-Gel Chemistry .............. .. ...............25...
1.6 Molecular Imprinting and Miniemulsion Polymerization .............. .....................2

2 EXPERIMENTAL TECHNIQUES............... ...............3

2.1 Langmuir Monolayers and Surface Pressure Related Experiments ................ ...............32
2.2 Langmuir-Blodgett Films and Atomic Force Microscopy .............. ....................3
2.3 Transmission Electron Microscopy and Quasi-Elastic Light Scattering ................... .......39
2.4 Cyclic Voltammetry............... ..............4

3 POLYSTYRENE-b-POLY(TERT-BUTYLACRYLATE) AND POLYSTYRENE-b-
POLY(ACRYLIC ACID) DENDRIMER-LIKE COPOLYMERS: TWO-
DIMENSIONAL SELF-AS SEMBLY AT THE AIR-WATER INTERFACE ....................44

3 .1 Introducti on ............ ..... ._ ...............44..
3.2 Results and Discussion ................. .... ...............4
3.2. 1 PS-b-PtBA Dendrimer-Like Copolymer ................. ...............46...............
3.2.2 PS-b-PAA Dendrimer-Like Copolymer ................. ........._.. ....... 52_.._ ...
3.3 Conclusions............... ..............5
3.4 Experimental Methods ..........._._ ......_..._ ...............59....
3 .4. 1 M ateri al s........._.___..... ._ __ ...............59..
3.4.2 Langmuir Films .............. ...............59....
3.4.3 AFM Imaging ................. ...............60..._..._ .....

4 LANGMUIR AND LANGMUIR-BLODGETT FILMS OF POLY(ETHYLENE
OXIDE)-b-POLY(s-CAPROLACTONE) STAR-SHAPED AND LINEAR BLOCK
COPOLY MERS .............. ...............61....











4. 1 Introducti on ................. ...............61._._ ._.....
4.2 Results and Discussion .............. ...............64....
4.2.1 PEO Homopolymers............... ..............6
4.2.2 PCL Homopolymers .................... ....__ ...............67..
4.2.3 Star-Shaped PEO-b-PCL Block Copolymers ......____ ........_ ................73
4.2.3.1 High MMA region............... ...............73.
4.2.3.2 Intermediate MMA region .............. ...............77....
4.2.3.3 Low MMA region .............. ...............79....
4.2.3.4 AFM imaging ............... .... ...............81.
4.2.4 PEO-b-PCL Linear Diblock Copolymers ................. .............. ...._.. ......83
4.2.4.1 Low surface pressure region .............. ...............85....
4.2.4.2 High surface pressure region............... ...............90.
4.3 Conclusions............... ..............9
4.4 Experimental Methods ................. ...............96........... ....
4.4.1 Langmuir Films .............. ...............96....
4.4.2 AFM Imaging ................. ...............97................

5 TWO-DIMENSIONAL POLYMERIC NANOMATERIALS THROUGH CROSS-
LINKING OF POLYBUTADIENE-b-POLY(ETHYLENE OXIDE) MONOLAYERS
AT THE AIR/WATER INTERFACE ................. ...............98................


5 .1 Introducti on ................. ...............98........... ...
5.2 Results and Discussion ................ .......... ...............100 ....
5.2. 1 Hydrosilylated PB Homopolymer ....__ ................ ............... 100 ...
5.2. 1.1 Hydrosilylation reaction ............... ....____ ...............100
5.2.1.2 Cross-linking reaction at the A/W interface............... ...............10
5.2. 1.3 AFM imaging ................. ... ......... ...............107....
5.2.2 Hydrosilylated PB-b-PEO Three-Arm Stars .............. ...............109....
5.2.2. 1 Hydrosilylation reaction ............... ....____ .....__ ..........12
5.2.2.2 Cross-linking reaction at the A/W interface ................. ......................115
5.2.2.3 AFM imaging ................. ...............119......... .....
5.3 Conclusions............... ..............12
5.4 Experimental Methods .................. ...............125...............
5.4. 1 Materials and Instrumentation ......___ ..... ..___ ...............125
5.4.2 Langmuir Films ............... ...... ..............12
5.4.3 Hydrosilylation of the PB Homopolymer.............. ... .... .. .. ............_ ...126
5.4.4 Hydrosilylation of the (PB200-b-PEO326)3 Three-Arm Star Block Copolymer....127
5.4.5 A/W Interfacial Cross-Linking ................. ...............128........... ...

6 ELECTROCHEMICAL AND SPECTROSCOPIC CHARACTERIZATION OF
ORGANIC COMPOUND UPTAKE IN SILICA CORE-SHELL NANOCAPSULES ......129


6. 1 Introducti on ............ ..... ._ ...............129..
6.2 Results and Discussion ............ ..... ._ ...............131..
6.2. 1 Nanocapsule Characterization ........_.._ ... ...._. ....._. ...........13
6.2.2 Uptake Study .............. ....... .. ............13
6.2.2. 1 Optical measurements results ..........._.. ......_. ....._.. ...........3












6.2.2.2 Electrochemical experiments .............. ...............138....
6.3 Conclusions............... ..............14
6.4 Experimental Methods ................. ...............147................
6.4. 1 Nanocapsule Synthesis ................ ...............147...............
6.4.2 Transmission Electron Microscopy ................. ...............147...............
6.4.3 Particle Size Analysis ................ ...............148...............
6.4.4 Spectroscopy Measurements .............. ...............148....
6.4.5 Electrochemistry Experiments ................. ...............149...............

7 TOWARD SPECIFIC DRUG DETOXIFICATION AGENTS: MOLECULARLY
IMPRINTED NANOPARTICLES................ ............15


7. 1 Introducti on ................. ...............151........... ...
7.2 Results and Discussion ................ ...............152...............
7.3 Conclusions............... ..............16
7.4 Experimental Section............... ...............161
7.4. 1 M ateri al s................. .......... ...............161...
7.4.2 Nanoparticle Synthesis ................ ...............162................
7.4.3 FTIR Spectroscopy ............ .......__ ...............162.
7.4.4 Particle Size Analysis ............ ...... ...............162.
7.4.5 AFM Imaging ................. ...............163...............
7.4.6 Uptake Experiments .............. ...............163....

8 CONCLUSIONS AND PERSPECTIVES .............. ...............165....


LIST OF REFERENCES ................. ...............168................


BIOGRAPHICAL SKETCH ................. ...............184......... ......










LIST OF TABLES


Table page

4-1 Characteristic values of the star-shaped polymers. ......___ .... ... .__. ........_........63

4-2 Characteristic values of the linear PEO macroinitiator and of the linear diblock
copolym ers. .............. ...............64....

4-3 Collapse pressure values of the PCL homopolymers. ................ ...._ ................69

5-1 Number average molecular weights and polydispersity indexes of the three-arm star
block copolymers ................. ...............110................

7-1 Loading compositions of the miniemulsions. ..........._.....___ .......___........15










LIST OF FIGURES


Figure page

1-1 Mean-field predication of the morphologies for conformationally symmetric diblock
m elts ................. ...............18.................

1-2 Solution state for amphiphilic diblock copolymers in water for concentrations below
and above the CM C. ............. ...............19.....

1-3 Spherical, rodlike, and vesicular morphologies for PS-b-PAA crew-cut micelles............20

1-4 A schematic illustration showing the components of an amphiphile and the
orientation of this amphiphile adopted at an interface ....._.__._ ... ......__ ........._.....21

1-5 Transmission electron micrographs of LB fi1ms of poly(styrene-b-vinylpyridinium
decyl iodide) AB diblock copolymers .............. ...............23....

1-6 Structure of normal and inverse spherical micelles formed in microemulsion systems....26

1-7 Sol-Gel hydrolysis and condensation reactions. ............. ...............27.....

1-8 Sol-Gel technologies and their products ................. ....__. ......._...........2

1-9 Outline of the molecular imprinting strategy ....._.._.. .... ... .__. ...._.._ .........2

1-10 Examples of commercially available functional monomers and cross-linkers ........._.......29

1-11 Principal of miniemulsion polymerization. ....._ .....___ ........___ ...............3 1

2-1 The Langmuir Teflon trough .............. ...............32....

2-2 A Wilhelmy plate partially immersed in a water subphase .............. .....................3

2-3 Schematic isotherm for small amphiphilic molecules .............. ...............35....

2-4 LB fi1m transfer onto a hydrophilic mica substrate .............. ...............37....

2-5 The AFM tapping mode electronic setup ......... .........._.... ......... ...........3

2-6 Specimen interactions in electron microscopy .............. ...............39....

2-7 Basic shape of the current response for a cyclic voltammetry experiment. ................... ....42

3-1 Schematic sketch of the PS-b-PtBA (Dendl) and the PS-b-PAA (Dend2) samples.........45

3-2 Isotherm of Dend1. (Inset) Static elastic modulus plot versus surface pressure. .............47










3-3 Topographic AFM images of Dendl LB fi1ms transferred at 5, 10, 15, 20, 24 (middle
of plateau, MMA = 20,000 A+2), and 40 mN/m ................. ............ ...................49

3-4 Compression-expansion hysteresis plot of Dend1 (target MMA = 20,000 A+2).................50

3-5 Surface pressure/time isochoric relaxation plot of Dend1 after compression up to 40
m N /m .............. ...............51....

3-6 Compression-expansion hysteresis plot of Dend1 (target pressure = 40 mN/m) ..............52

3-7 Isotherm of PAA250K (pH = 2.5). ................ ......... ......... ........ ..............53

3-8 Topographic AFM images of PAA250K LB fi1ms transferred at 1.5, 3, and 3.5 mN/m. ....54

3-9 Isotherm of Dend2 (pH = 2.5). (Inset) Compressibility plot versus surface pressure. ......55

3-10 Topographic AFM images of Dend2 LB fi1ms transferred at 2, 4, 4.5, 5, 5.5, 6, and 8
m N /m ............. ...............57.....

3-11 Compression-expansion hysteresis plot of Dend2 (target pressure = 5 mN/m, pH =
2.5). ............. ...............57.....

4-1 The star-shaped PEO-b-PCL block copolymers. ............. ...............63.....

4-2 The linear PEO-b-PCL block copolymers. ............. ...............64.....

4-3 Isotherms of the PEO homopolymers. (Inset) Same isotherms normalized with
respect to the number of ethylene oxide units. ............. ...............66.....

4-4 Compression-expansion hysteresis plot of the PEO core (target pressure = 2 mN/m)......66

4-5 Isotherms of the PCL homopolymers. (Inset) Same isotherms normalized with
respect to the number of e-caprolactone units. ............. ...............68.....

4-6 Isotherms of the PCL homopolymers (compression speed = 100 mm/min). ....................70

4-7 Compression-expansion hysteresi s plot of PCL 1250. ................ ....._._ ........_......7 1

4-8 Topographic AFM images of PCL homopolymers LB fi1ms transferred below and
above monolayer collapse ................. ...............72........... ....

4-9 Isotherms of the star-shaped PEO-b-PCL copolymers. ......... ................ ...............73

4-10 Compression-expansion hysteresis plot of Star#6 (target pressure = 9 mN/m). ...............74

4-11 Compression-expansion hysteresis plot of Star#1 (target pressure = 9 mN/m). ...............74

4-12 Plots of MMA versus number of e-caprolactone repeat units for different surface
pressures from the isotherms of Star#3, Star#4, Star#5, and Star#6 .............. ..............76










4-13 Isotherms of the PEO core extrapolated and PEO2000 normalized with respect to the
number of ethylene oxide units. ................. ...............76.._._._ ....

4-14 Compressibility plots of the star-shaped PEO-b-PCL block copolymers versus
surface pressure............... ...............77

4-15 Isobaric relaxation plots of Star#6 at 9, 11, and 13 mN/m ................. .......................78

4-16 Compression-expansion hysteresis plot of Star#6 (target pressure = 15 mN/m) ........._....79

4-17 Compression-expansion hysteresis plot of Star#1 (target pressure = 15 mN/m) ........._....79

4-18 Proposed conformations modeling the adsorption of the star-shaped block
copolymers at the A/W interface versus surface pressure. ............. .....................8

4-19 Topographic AFM images of the star-shaped PEO-b-PCL copolymers LB films
transferred below and above the pseudoplateau .............. ...............82....

4-20 Isotherms of the PEO-b-PCL linear diblock copolymers. ................ ................. .....84

4-21 Compressibility plots of the PEO-b-PCL linear diblock copolymers versus surface
pressure. ............. ...............8 5....

4-22 Isotherms of PEO2670 and PCL2000 binary mixtures. (Inset) Corresponding
compressibility plots versus surface pressure. .............. ...............86....

4-23 Compression-expansion hysteresis plot of the binary mixture with 49 mol % in
PEO2670 (target pressure = 9 mN/m). ............. ...............86.....

4-24 MMA plots versus mole fraction of PCL2000. Dashed lines: theoretical ideal mixing....87

4-25 Compression-expansion hysteresis plot of PEO60-b-PCL11 (target pressure = 18
m N /m ). .............. ...............89....

4-26 Compressibility plots of Figure 4-25 (PEO60-b-PCLll, target pressure = 18 mN/m).......89

4-27 Compression-expansion hysteresis plot of PEO60-b-PCL35 (target pressure = 16
m N /m ). .............. ...............9 1....

4-28 Compressibility plots of Figure 4-27 (PEO60-b-PCL35, target pressure = 16 mN/m)........92

4-29 Topographic AFM images of the linear PEO-b-PCL diblock copolymers LB films
transferred after crystallization of the PCL segment at the A/W interface (7<= 15
m N/m ) ................. ...............93.......... ......

4-30 Proposed conformations modeling the adsorption of the linear PEO-b-PCL diblock
copolymers at the A/W interface versus surface pressure .............. .....................9

5-1 Hydrosilylation of the pendant double bonds of the PB homopolymer. ........................101










5-2 1H NMR spectrum of the PB homopolymer ................. ...............101.............

5-3 1H NMR spectrum of the hydrosilylated PB homopolymer............._ .........._ .....102

5-4 FTIR spectra of the PB homopolymer before and after hydrosilylation. ........._.............102

5-5 Cross-linking reaction involving hydrolysis and condensation of the triethoxysilane
groups ................. ...............104................

5-6 Surface pressure-Mean Molecular Area isotherms of the hydrosilylated PB carried
out after different reaction times (subphase pH = 3.0). ............. ....................10

5-7 Static elastic modulus-surface pressure curves of the hydrosilylated PB
homopolymer at different reaction times (subphase pH = 3.0). ............. ....................105

5-8 MMA-time isobars of the hydrosilylated PB for various subphase pH values (ri= 10
m N /m ). .............. ...............106....

5-9 Removal of the cross-linked hydrosilylated PB from the water surface ......................107

5-10 AFM topographic images of the LB films transferred onto mica substrates at zi= 10
m N /m ............. ...............109....

5-11 Surface Pressure-MMA isotherms for the (PB200-b-PE0n)3 three-arm star block
copolymers. ........._.._.. ...._... ...............111....

5-12 Isotherm of (PB76-b-PEO444)4 depicting how Apancake, Ao, and AApseudoplateau are
determ ined............... ..............11

5-13 Linear dependence of AApseudoplateau On the total number of ethylene oxide units............1 12

5-14 Hydrosilylation of the pendant double bonds of the (PB-b-PEO)3 three-arm star
block copolymers. ........... ..... .._ ...............113...

5-15 1H NMR spectra of the (PB200-b-PEO326)3 Star block copolymer and the
corresponding hydrosilylated (PB(Si(OEt)3)-b-PEO)3 Star block copolymer. ................114

5-16 FTIR spectra of the (PB200-b-PEO326)3 Star block copolymer and the corresponding
hydrosilylated (PB(Si(OEt)3)-b-PEO)3 Star block copolymer. ................ ................. .114

5-17 Surface Pressure-MMA isotherms of the (PB200-b-PEO326)3 Star block copolymer and
of the corresponding hydrosilylated (PB(Si(OEt)3)-b-PEO)3 Star block copolymer
before and after cross-linking. ........... ......... ...............116.....

5-18 Surface Pressure-MMA isotherms and compressibility-MMA curves of the
hydrosilylated (PB(Si(OEt)3)-b-PEO)3 Star block copolymer at various reaction times
(subphase pH = 3.0). ........... ......_._ ...............117...










5-19 Isobars of the hydrosilylated (PB(Si(OEt)3)-b-PEO)3 Star block copolymer for
various subphase pH values (7<= 5 mN/m) ................. ...............118.............

5-20 Removal of the cross-linked (PB(Si(OEt)3)-b-PEO)3 three-arm star copolymer from
the Langmuir trough surface. ........._.__ ..... .___ ...............119...

5-21 AFM topographic images of the (PB(Si(OEt)3)-b-PEO)3 Star block copolymer LB
film s. ............. ...............122....

5-22 Cross-section analysis of Figures 5-21D and 5-21H, PEO pore size versus surface
pressure plot, and PSD plots of Figures 5-21C, 5-21D, 5-21G, and 5-21H. ...................122

5-23 AFM topographic images and corresponding cross-sections of the (PB(Si(OEt)3)-b-
PEO)3 Star block copolymer LB films cross-linked at 9 mN/m (pH = 3.0, t = 10 h)
and transferred at 9 and 2 mN/m............... ...............123.

5-24 Surface pressure-MMA isotherms of the hydrosilylated (PB(Si(OEt)3)-b-PEO)3 Star
block copolymer cross-linked at 5 and 20 mN/m (pH = 3.0, t = 10 h). ........._................124

6-1 Oil-filled silica nanocapsule synthesis through initial hydrophobic core formation
followed by hydrophilic silica shell formation after TMOS addition..............................132

6-2 Description of the nanocapsule samples prepared using 0.07, 0.28, 0.44, and 0.88 wt
% TM OS. ............. ...............132....

6-3 DLS results for the microemulsion immediately after preparation and the same
solution after TMOS addition (0.07 wt %) and dialysis. ................ .................13

6-4 TEM micrographs of the 0.07 wt % TMOS nanocapsules and of the 0.88 wt %
TM OS nanocapsules. ............. ...............134....

6-5 Chemical structures of ferrocene methanol, ferrocene dimethanol, and Nile Red. .........135

6-6 UV-vis absorption spectra of iodine in water solution, in nanocapsule solution, in
Tween-80 aqueous solution, and in ethyl butyrate solution. ............. .....................3

6-7 Nile Red emission spectra in ethyl butyrate solution, in nanocapsule solution, in
Tween-80 aqueous solution, in crushed Xerogel dispersion in acidic water, on silica
gel, and in acidic water solution. ............. ...............137....

6-8 Typical cyclic voltammogram of ferrocene methanol in water. ..........__.... ................ 138

6-9 Uptake of ferrocene methanol versus time in 0.07, 0.28, 0.44, and 0.88 wt % TMOS
nanocapsule solutions. ............. ...............141....

6-10 Plot of normalized aqueous concentration of ferrocene methanol after uptake in 0.07,
0.28, 0.44, and 0.88 wt % TMO S nanocapsule solutions ..........._... ........._............142











6-11 Uptake of ferrocene dimethanol versus time in 0.07, 0.28, 0.44, and 0.88 wt %
TMOS nanocapsule solutions .............._ ...............144........ .....

6-12 Uptake of ferrocene methanol versus time in 0, 2, 4, 6, and 8 wt % Tween-80
aqueous solutions ................. ...............145................

6-13 Uptake of ferrocene dimethanol versus time in 0, 2, 4, 6, and 8 wt % Tween-80
aqueous solutions ................. ...............146................

7-1 Chemical structures of amitriptyline and bupivacaine. ....._____ ........._ ........._....152

7-2 The molecular imprinting strategy in miniemulsion polymerization. ............. ................154

7-3 IR absorbance spectra of EGDMA, MIP1, and MIP3 ................. ................ ...._..155

7-4 DLS size distribution of MIP6............... ...............156

7-5 Tapping mode topographical AFM images and cross-section analysis of MIP6............. 157

7-6 Uptake of amitriptyline by the non-molecularly imprinted nanoparticles MIP1, MIP2,
and M IP3 .............. ...............158....

7-7 Uptake of amitriptyline by the nanoparticles molecularly imprinted with
amitriptyline: MIP4, MIPS, and MIP6............... ...............159.

7-8 Uptake of bupivacaine by the nanoparticles molecularly imprinted with
amitriptyline: MIP4, MIPS, and MIP6............... ...............160.









Abstract of Dissertation Presented to the Graduate School
of the University of Florida in Partial Fulfillment of the
Requirements for the Degree of Doctor of Philosophy

TWO-DIMENSIONAL SELF-ASSEMBLY OF AMPHIPHILIC BLOCK COPOLYMERS AT
THE AIR/WATER INTERFACE AND NANOPARTICLES FOR DRUG DETOXIFICATION
APPLICATIONS

By

Thomas J. Joncheray

December 2006

Chair: Randolph S. Duran
Major Department: Chemistry

The two-dimensional self-assembly at the air/water (A/W) interface of various block

copolymers (dendrimer-like polystyrene-b-poly(tert-butylacrylate) (PS-b-PtBA) and

polystyrene-b-poly(acrylic acid) (PS-b-PAA), linear and five-arm star poly(ethylene oxide)-b-

poly(s-caprolactone) (PEO-b-PCL), and three-arm star triethoxysilane-functionalized

polybutadiene-b-poly(ethylene oxide) (PB(Si(OEt)3)-b-PEO)) was investigated through surface

pressure measurements isothermss, isobars, isochores, and compression-expansion hysteresis

experiments) and atomic force microscopy (AFM) imaging. The PS-b-PtBA and the PS-b-PAA

samples formed well-defined circular surface micelles at low surface pressures with low

aggregation numbers (~ 3-5) compared to linear analogues before collapse of the PtBA chains

and aqueous dissolution of the PAA segments take place around 24 and 5 mN/m, respectively.

The linear PEO-b-PCL samples exhibited three phase transitions at 6.5, 10.5, and 13.5 mN/m

corresponding respectively to PEO aqueous dissolution, PEO brush formation, and PCL

crystallization. The two PEO phase transitions were not observed for the star-shaped PEO-b-PCL

samples because of the negligible surface activity of the star-shaped PEO core compared to its

linear analogue. The PB(Si(OEt)3)-b-PEO sample was cross-linked at the A/W interface by self-









condensation of the pendant triethoxysilane groups under acidic conditions, which resulted in the

formation of a two-dimensional PB network containing PEO pores with controllable sizes.

With a view toward drug detoxification therapy, the encapsulation abilities of oil core-

silica shell nanocapsules and molecularly imprinted nanoparticles were also investigated by

electrochemical (cyclic voltammetry) and optical (fluorescence and UV-vis spectroscopies)

techniques. The core-shell nanocapsules were shown to efficiently remove large amounts of

organic molecules present in aqueous solutions, with the silica shell acting analogously to a

chromatographing layer. The molecularly imprinted nanoparticles were prepared by the non-

covalent approach and by miniemulsion polymerization. Binding studies on the molecularly

imprinted nanoparticles in aqueous solutions under physiological pH conditions indicated that, in

the absence of specific imprinting, the uptake of toxic drugs was mainly driven by non-specific

hydrophobic interactions. As demonstrated with the use of the antidepressant amitriptyline, in the

presence of specific imprinting the uptake significantly increased as the amount of specific

binding sites was increased.









CHAPTER 1
INTTRODUCTION

This dissertation aims at summarizing the work realized on two different research domains

of polymer chemistry: the air/water (A/W) interfacial behavior of block copolymers and the

synthesis of nanoparticles for drug detoxification applications. As presented in Chapters 3, 4, and

5, the first three research projects are related to the self-assembly of amphiphilic block

copolymers at the A/W interface, whereas Chapters 6 and 7 describe the investigations carried

out on the possibility for 2 different types of nanoparticulate systems to be used as drug

detoxification agents. While Chapter 2 briefly describes the principal experimental techniques

mentioned in the subsequent chapters, this first introductory chapter serves as literature

background for the different research proj ects and also defines the key concepts used throughout

this dissertation.

1.1 Block Copolymers in the Bulk and in Solution

"Block copolymer" is a general term used to define a macromolecule composed of

different polymer chains. The field of block copolymers has attracted a lot of interest in the past

thirty years because the eventual phase separation between immiscible blocks in various

environments, such as in the bulk, often leads to well-defined self-assembled structures with

unique morphologies with characteristic sizes ranging between a few nanometers up to hundreds

of nanometers.1,2 Moreover, the recent emergence of controlled polymerization techniques such

as living anionic polymerization,3 ATRP (atom transfer radical polymerization),4 Or RAFT

(reversible addition fragmentation chain transfer)' has allowed access to a variety of

compositions and architectures (star,6 mikto-arm,7 cyclic .), which significantly increases the

diversity of peculiar and regular patterns obtainable resulting from their self-assembly. A lot of

research still has to be done to better understand the relationships between block copolymer









architecture and self-assembly. Therefore, because of their simple architecture, linear diblock

copolymers are still currently the best-known class of block copolymers. Several theoretical

models have been proposed to describe the behavior of block copolymers such as for instance the

self-consistent field theory (SCFT)9 Or the mean-field theory (MFT)1o where the phase behavior

is dictated by the Flory-Huggins segment-segment interaction parameter, the degree of

polymerization, and the composition. As an example, if the two A and B blocks of a linear AB

diblock copolymer are immiscible, they can adopt in the bulk, as shown in Figure 1-1, various

microphase morphologies such as spheres (S and S'), cylinders (C and C'), double gyroids (G

and G'), or lamellae (L).1"












Figure 1-1. Mean-field predication of the morphologies for conformationally symmetric diblock
melts. Phases are labeled as: S (spheres), C (cylinders), G (double gyroids), L
lamellaee). fA is the volume fraction.1c

When block copolymers are dissolved in a selective solvent, the chains can aggregate to

reversibly form well-defined micelles above the so-called critical micellar concentration (CMC).

For concentrations lower than the CMC, block copolymer molecules are unassociated as

illustrated in Figure 1-2 for amphiphilic diblock copolymers in water aggregating into spherical

micelles.













t ~ ~Hydrophilic block c 12 J ecc
Hydrophobic block

















C < CMC C > CMC

Figure 1-2. Solution state for amphiphilic diblock copolymers in water for concentrations below
and above the CMC.

The critical micellar concentrations of block copolymers are usually very low compared to

low molecular weight surfactants, and therefore the micelles formed have great potential in drug

delivery when used as nanocontainers since they hardly dissociate in the blood stream, even

under highly dilute conditions.1a Depending on the architecture, composition, concentration, or

solvent, block copolymers can aggregate into a variety of micellar structures. Figure 1-3 shows

as an example some peculiar morphologies obtained by Eisenberg and co-workers for "crew-cut"

micelles of linear polystyrene-b-poly(acrylic acid) (PS-b-PAA) diblock copolymers in aqueous

solutions."l Transitions from spheres to rod to vesicles were observed as the length of the PAA

segment was decreased. In semi-dilute or concentrated solutions, gelation normally occurs, and

block copolymer micelles organize into a nanostructure-ordered lyotropic liquid crystal phase.12



























Figure 1-3. Spherical (a), rodlike (b), and vesicular (c) morphologies for PS-b-PAA crew-cut
micelles.ll

1.2 Block Copolymers at the A/W Interface

The behavior of block copolymers at interfaces is also of great interest since other

parameters such as the surface energies as well as film thickness can strongly influence the

microphase separation.l" Confining polymeric chains in a layer thinner than their natural length

scale (the radius of gyration) considerably alters their conformation and the resulting physical

properties compared to the bulk properties.13 Among the variety of surfaces and interfaces

available, the A/W interface has attracted a lot of attention because it allows the easy formation

of two-dimensional polymeric monolayers (Langmuir monolayers), providing that the block

copolymers studied are surface active by having sufficiently polar functional groups to adsorb at

the interface (without being too much water soluble to avoid their irreversible dissolution in the

aqueous subphase). Similarly as for low molecular weight surfactants, surface active block

copolymers self-assemble at the A/W interface to reduce the surface tension (internal pressure

caused by the attraction of molecules below the surface for those at the surface) with the

hydrophilic segments immersed into the water and the hydrophobic segments desorbed in the air

as illustrated in Figure 1-4 for a low molecular weight fatty acid amphiphile.14


, C
I ~















Hydrocarbons
Chain
ACir, Gas olr Oil









Figure 1-4. A schematic illustration showing the components of an amphiphile and the
orientation of this amphiphile adopted at an interface.14

As previously shown, one of the great advantages of the A/W interface is that it is possible

and fairly easy to accurately control and adjust the way the chains of the block copolymers self-

assemble simply by varying their surface concentration (amount present at the interface) in

addition to the other usual parameters mentioned before for the bulk or for solutions. This often

leads to peculiar arrangements of the polymer chains with the formation of surface micelles,

which significantly differs from what is commonly observed for low molecular weight

amphiphiles. Control of surface density in the Langmuir films and transfer of the block

copolymer monolayers onto solid substrates for further analysis (Langmuir-Blodgett films) are

experimental procedures commonly done with the use of a Langmuir trough as extensively

described later in Chapter 2. A wide range of experimental techniques can be used for

morphology investigation in Langmuir and Langmuir-Blodgett (LB) monolayers including

neutron and X-ray reflectivity, surface pressure and potential measurements, Brewster angle

microscopy (BAM), atomic force microscopy (AFM), transmission electron microscopy (TEM),

and ellipsometry.15-20 Examples of block copolymers with various architectures previously









studied at the A/W interface include poly(ethylene oxide)-b-poly(propylene oxide) (PEO-b-

PPO), polystyrene-b-poly(ethylene oxide) (PS-b-PEO), polybutadiene-b-poly(ethylene oxide)

(PB-b-PEO), and polystyrene-b-polyacrylate.21-24 Block copolymers based on PS and decylated

poly(4-vinylpyridine) (decylated P4VP) have also been extensively investigated at the A/W

interface by Eisenberg and co-workers, and some of their results are presented here to illustrate

the concept of surface micelle formation. Surface micelle formation results from the presence at

the A/W interface of immiscible blocks that phase separate because of sufficiently different

polarities. In the case of PS and decylated P4VP-based block copolymers, only the hydrophilic

decylated P4VP segments adsorb at the A/W interface with the hydrophobic PS segments

desorbing and aggregating above the interface. This results in the formation of well-defined

surface micelles with architectures evolving from circular to rod-like to planar as the PS % in the

diblock copolymers is increased (Figure 1-5).25 Prospective applications of such well-defined

patterns with feature sizes typically in the nanometer scale order include lithographic masks,

photonic materials, and nanopatterned substrates for microelectronics.26-28

The results presented in Chapters 3, 4, and 5 of this dissertation are all related to the self-

assembly of block copolymers at the A/W interface. While the work presented in Chapters 3 (on

polystyrene-b-poly(tert-butylacrylate) and polystyrene-b-poly(acrylic acid) dendrimer-like block

copolymers) and 4 (on linear and star-shaped poly(ethylene oxi de)-b-poly(e-caprol actone) block

copolymers) describes the interfacial aggregation of several block copolymers on a fundamental

level, the work presented in Chapter 5 (on star-shaped poly(ethylene oxide)-b-hydrosilylated

polybutadiene block copolymers and done in collaboration with Rachid Matmour, graduate

student in the Duran group at the University of Florida) focuses primarily on the use of a post









monolayer formation cross-linking method using Sol-Gel chemistry (Section 1-5) for the

synthesis of novel two-dimensional cross-linked nanomaterials with well-defined morphologies.


Figure 1-5. Transmission electron micrographs of LB films of poly(styrene-b-vinylpyridinium
decyl iodide) AB diblock copolymers (surface pressure = 2 mN/m) (a) P(S260-b-
VP120 10oI); % PS = 68.4; (b) P(S260-b-VIP71/Clol); % PS = 78.5; (C) P(S260-b-
WP29 C0I) % PS = 90 .0; (d) P(S480-b-VP34C10I) % PS = 93 .4; (e) P(Slso-b-VP11/Clol)
% PS = 94.2; (f) P(S480-b-VPl3 C10I) % PS 97.4.25

1.3 Current Status of Drug Detoxification Therapy

Drug toxicity is a major health concern, because more than 3 million insecticide

poisonings are reported every year worldwide with, among them, around 200,000 fatal cases.29

In the United States, a 2000-query showed that drug-related complications lead to the hospi-

talization of more than 300,000 patients per year. Other important issues are related to clinical

mistreatment for instance in the area of anesthesiology where it was recently shown that the









intravenous injections of local anesthetics such as bupivacaine are a major cause of cardiac

blocks with a fatal outcome.30,31 Tricyclic antidepressants such as amitriptyline (one of the most

common drugs used in suicideS32) are among the most frequently ingested substances in self-

poisoning.33 COmmon clinical treatments in the case of anesthetic-induced toxicity include rapid

oxygenation, ventilation, seizure control, and cardiovascular support.34 To Eight drug overdose,

several methods have been explored such as the intravenous injection of sodium bicarbonate,35

the use of activated carbon,36 the use of lipid infusions,37 Or even the use of other drugs such as

amiodarone,38 inSUlin,39 Or propofol.40 All these methods have shown some interesting results but

an efficient and specific antidote scavenging the toxicity of the aforementioned antidepressant

and anesthetic drugs by reducing their bio-availability within the body still has to be designed.

1.4 Nanoparticle Technology

Living organisms are built of cells that are usually a few micrometers in size, and their

organelles are even much smaller, in the sub-micron size range. The recent development of

nanotechnologies that deal with nanometer-sized objects (nanoparticles) for instance in

electronics, cosmetics, or catalysis41,42 also opened the possibility to probe the cellular machinery

without introducing too much interference43 and to understand biological processes on the

nanoscale level.44 Recent developments of nanoparticulate systems include for instance protein

detection,45 tissue engineering,46 cancer therapy,47 and drug delivery.48 Because of the absence of

specific antidotes in the case of drug intoxication as mentioned in the previous paragraph, a

multidisciplinary effort is being made at the University of Florida (Particle Engineering Research

Center and Departments of Chemistry, Material Science, Chemical Engineering, and

Anesthesiology) to synthesize a series of novel nano-sized bioparticles that are able to move

freely in the blood stream even in the smallest capillaries (diameter ~ 5 pum) and that are able to









effectively reduce the free blood concentration of toxic drugs. The ideal nanoparticulate system

therefore should have high and fast (within seconds or minutes) encapsulation capacities, should

be biocompatible (non-toxic), biodegradable (slowly enough so the aqueous concentration of the

drug released in the blood stays below toxic levels), and above all, should be specific to the

target drug to avoid side encapsulation of other undesired molecules present in the blood stream.

Oil core-silica shell nanocapsules have been recently synthesized in the Duran group by

combining microemulsion formulation and Sol-Gel chemistry,49 and with a view toward their

application in detoxification media, the work presented in Chapter 6 focused on investigating

their uptake kinetics and capacities of drug-mimicking compounds. In Chapter 7, a different and

novel type of nanoparticles was synthesized and characterized by combining miniemulsion

polymerization and molecular imprinting technology in an attempt to design a nanoparticulate

system with increased selectivity.

1.5 Microemulsions and Sol-Gel Chemistry

A microemulsion is defined as a system comprising oil, water, and surfactants (surface

active agents having both a hydrophilic part and a hydrophobic part) that results in a single-

phase, optically isotropic, and therefore thermodynamically stable liquid solution. This is not the

case for emulsions that are usually only kinetically stable and that coalesce and phase-separate

over time. When water, oil, and surfactants are mixed together to form a microemulsion, the

surfactant molecules rest at the oil-water interface with the hydrophilic groups solubilized into

the aqueous phase and the hydrophobic groups solubilized into the organic phase to avoid the

direct oil-water contact. The sizes of these structures are usually in the range of a few hundred

nanometers, which makes them suitable for the synthesis of nano-sized objects. Depending on

several parameters such as the nature of the oil or of the surfactant and the concentrations or the

relative amounts of oil, surfactant, and water used, it is possible to obtain a variety of internal









structures. They can be spherical (Figure 1-6), spheroidal, or cylindrical "rod" or "worm-like"

micelles, and they may exist in hexagonal, cubic, or lamellar phases. Alternatively, a range of

bicontinuous phases may exist.















Figure 1-6. Structure of normal (left) and inverse (right) spherical micelles formed in
microemulsion systems.

Microemulsions can have characteristic properties such as ultra low interfacial tension,

large interfacial area and capacity to solubilize both aqueous and oil-soluble compounds.'o

Therefore, they can be used in a variety of applications, for example in enhanced oil recovery,"

as fuels,52 as lubricants, cutting oils, and corrosion inhibitors,53 as coatings and textile finishing,54

in detergency," in cosmetics,56 in food,57 in pharmaceuticals,58 or in biotechnology.59 As

presented in Chapter 6, an oil-in-water microemulsion system composed of spherical micelles

was designed in an attempt to selectively encapsulate hydrophobic toxic drugs inside the micellar

oil core and to decrease their free concentration in the blood stream. Even though microemulsion

systems are thermodynamically stable, the high dilution taking place after their injection inside

body fluids would lead to rupture and further coalescence of the micellar structures. This

problem can be avoided by building a solid shell surrounding the microemulsion oil droplets that

will not break upon dilution, for instance by the means of Sol-Gel chemistry (hence the name

core-shell nanocapsules).









The Sol-Gel process allows the easy synthesis of ceramic and glass materials with high

purities and homogeneities by using preparation techniques different from the traditional process

of fusion of oxides. This process occurs in liquid solutions in the presence of organometallic

precursors such as metal alkoxides (tetramethoxysilane, tetraethoxysilane, Zr(IV)-propoxide, or

Ti(IV)-butoxide), which, through acid- or base-catalyzed hydrolysis and condensation reactions

as shown in Figure 1-7, leads to the formation of a new phase (Sol).60

M-O-R + H20 -- M-OH + R-OH (Hydrolysis)

M-OH + HO-M -- M-O-M + H20 (Water condensation)

M-O-R + HO-M M-O-M + R-OH (Alcohol condensation)

( M = S i, Z r, T i)

Figure 1-7. Sol-Gel hydrolysis and condensation reactions.

The Sol is made of solid particles of a diameter of a few hundred nanometers suspended in

a liquid phase. The particles then condense in a new phase (Gel) in which a solid macromolecule

is immersed in a liquid phase (solvent). Drying the Gel by means of low temperature treatments

allows the formation of materials in a wide variety of forms: ultra-fine or spherical shaped

powders, thin film coatings, ceramic fibers, microporous inorganic membranes, monolithic

ceramics and glasses, or extremely porous aerogel materials as illustrated in Figure 1-8.61 Sol-Gel

materials can be used for instance in chemical sensing,62 drug delivery,63 Or electrochromics.64

As further explained in Chapter 6, the formation of a rigid shell to impart stability to the

microemulsion droplets resulting in the formation of core-shell nanocapsules was done by

polycondensation of tetramethoxysilane directly on the microemulsion droplet surface previously

functionalized with trimethoxysilane groups. A similar polycondensation method was also used

as presented in details in Chapter 5 to cross-link in two dimensions block copolymers containing

triethoxysilane-functionalized polybutadiene segments at the A/W interface.





XnrogelfilmDaefb



Weirget


X~rogel DenlSe
Eglegraulian 'w Oi


Figure 1-8. Sol-Gel technologies and their products.61

1.6 Molecular Imprinting and Miniemulsion Polymerization

The concept of molecularly imprinted polymers (MIPs) was first introduced by Wulff

nearly thirty years ago.65 Since then, the methodology has undergone a number of important

developments, and MIPs have been used in a wide range of techniques (in solid-phase extraction,

as biosensors, as catalysts, and as binding assays) and approaches covalentt, non-covalent, metal

coordination).66-7 MIPs result from the polymerization of monomeric units in the presence of a

template molecule. The imprinting strategy investigated in Chapter 7 is shown in Figure 1-9 and

uses the non-covalent imprinting approach first developed by Mosbach.73,74 Functional

monomers are associated with a template via non-covalent interactions. The complex is then

copolymerized with a cross-linking monomer, followed by removal of the template using

extraction procedures. Removal of the template results in cavities whose shape, size,

functionality, and spatial arrangement are complementary to the imprinted molecule. These









recognition sites with predetermined selectivity enable MIPs to rebind selectively the original

template from a mixture. In principle, MIPs can be made with selectivity for essentially any of a

diverse range of analyte species, such as drug enantiomers, pesticides, hormones, toxins, short

peptides, and nucleic acids.75s


Figure 1-9. Outline of the molecular imprinting strategy.

Many parameters can affect the efficiency of the synthetic molecularly imprinted polymers

such as the porogen (solvent), the polymerization technique, and also the relative concentrations

of the functional monomer, cross-linker, template molecule, and initiator. Figure 1-10 shows

examples of classical functional monomers and cross-linkers commercially available for radical

polymerization.8





-O


Functional monomers

i~ CHa~ 0 CH

0 CH, OCH,
Crosslinkers

Figure 1-10. Examples of commercially available functional monomers and cross-linkers.8









The main motivation to investigate the potential of molecularly imprinted materials for

drug detoxification applications was to harvest their remarkable ability to rebind specifically a

variety of compounds including toxic drugs. As described later in further details (Chapter 7), the

synthesis of nano-sized molecularly imprinted particles was attempted through miniemulsion

radical polymerization, and their toxic drug-rebinding capacities were investigated.

Miniemulsions are produced by the combination of a high shear to break up the emulsion into

submicron monomer droplets and a surfactant/costabilizer system to retard monomer diffusion

from the submicron monomer droplets.82 The costabilizer is used to prevent Ostwald ripening.83

Compared to microemulsions that usually lead to the formation of oil droplets ranging from 10 to

100 nm, the formation of miniemulsions, which requires a lower amount of surfactants, usually

leads to oil droplet diameters ranging from 50 to 500 nm. The droplet surface area in these

systems is very large, and most of the surfactants are adsorbed at the droplet surface. Since little

surfactant is present in the form of micelles in a properly formulated microemulsion, particle

nucleation during polymerization primarily takes place inside the monomer droplets. This leads

to a 1:1 correspondence between the initial monomer droplets and the final polymer

nanoparticles. The principal of miniemulsion polymerization is schematically shown in Figure 1-

11. As described in greater details in Chapter 7, the synthesis of molecularly imprinted

nanoparticles was done radically, but the miniemulsion polymerization process is not limited to

radical polymerizations.84-86 The imprinting takes place inside the monomer droplets, and

extraction of the toxic drug molecules results in porous nanoparticles with recognition sites

complementary in shape to the original toxic drug template.









Emul sifier


.0 on ome 1

Mon omy Ir Polymer-





Mi ni emul sifi cati on P olymerizati on
(high pressure homogeniz er
or ultrasound)

Figure 1-11i. Principal of miniemulsion polymerization.









CHAPTER 2
EXPERIMENTAL TECHNIQUES

In this chapter, an overview of the principal experimental techniques is presented. The

specific detailed experimental procedures are not described here but are included instead at the

end of each of the following chapters in the Experimental sections.

2.1 Langmuir Monolayers and Surface Pressure Related Experiments

As further detailed in Chapters 3, 4, and 5, investigation of block copolymer self-assembly

at the air/water (A/W) interface in Langmuir monolayers requires the use of a Langmuir trough.

A typical set-up is shown in Figure 2-1. It provides a very simple method to control monolayer

surface density thanks to the movable barriers controlled by a DC motor. The trough is

composed of an inert material such as for instance Teflon polytetrafluoroethylenee, PTFE) that is

resistant to water absorption.

Balance Amphiphilic

r Block copolymers
S_-Wilhelmy plate


Teflonm trough IMilli-Q Water


Figure 2-1. The Langmuir Teflon trough.

To form a Langmuir monolayer, the block copolymer of interest is first dissolved in a

solvent (C 1mg/mL) which is then spread dropwise on the water surface. The solvent must be

hydrophobic to prevent its dissolution in the water subphase and so it doesn't influence the

surface pressure measurements. It should be also volatile enough to quickly evaporate from the

surface after spreading, leaving behind the adsorbed block copolymer molecules. Chloroform

was the solvent of choice in this dissertation except in Chapter 2 where the use of a more polar









chloroform/ethanol mixture was necessary to dissolve the polystyrene-b-poly(acrylic acid)

dendrimer-like block copolymer sample. Other commonly used solvents include n-hexane,

benzene, diethyl ether, as well as mixtures such as for instance hexane-ethanol, benzene-ethanol,

or chloroform-methanol .s After spreading, the surface active block copolymers expand to form

an adsorbed monolayer that quickly covers the entire available area present between the barriers.

In addition to the A/W interface which is the most commonly studied interface, others are

possible such as oil/water interfaces or gas (different from air)/water interfaces.













Figure 2-2. A Wilhelmy plate partially immersed in a water subphase.

The surface pressure measurements were achieved by use of the Wilhelmy plate technique

as shown in Figure 2-2.87 The surface tension (s)~ is defined by Equation 2-1,

ai = To 7 = -A7 (2-1)

where To represents the surface tension of the water subphase in the absence of an adsorbed

monolayer, and 7 represents the surface tension of the water subphase in the presence of an

adsorbed monolayer. Water is a very interesting subphase when investigating monolayers since it

has an exceptionally high surface tension (- 73 mN/m at 20 oC and under atmospheric

pressure"') that allows a wide range of surface pressures to be obtained. When the Wilhelmy

plate is partially immersed into the subphase, the forces acting consist of gravity and surface









tension downward as well as an upward buoyancy due to displaced water. The resulting force F

is monitored and related to the surface tension yas shown in Equation 2-2:

F = p,~g/wf + 27(t +w) cos p ghutl (2-2)

where p, and ps correspond to the densities of the Wilhelmy plate and the subphase, respectively,

g corresponds to the gravitational constant, t (thickness), w (width), and I (length) are the

dimensions of the Wilhelmy plate, B is the contact angle made by the subphase onto the plate (6

= 0 for a completely wetted plate, cos8= 1), and h corresponds to the plate height immersed into

the subphase. When measuring the change in F (AF) for a stationary plate after formation of an

adsorbed Langmuir monolayer, assuming that t is negligible compared to w, the equation can be

reduced to:

AF = 2wA7 (2-3)

and therefore, the surface pressure riis directly related to the change in force and the width of the

plate:


x = (2-4)
2w

With the Wilhelmy plate technique, the sensitivity can be as low as 5x10-3 mN/m. Nevertheless,

since very small amounts of impurities can affect surface pressure measurements, the water

subphase consists of Millipore filtered water with resistivities greater than 18.2 MGZ.cm.

Moreover, the trough needs to be carefully cleaned for instance with ethanol before forming a

Langmuir monolayer and rinsed several times with Millipore filtered water. Contamination with

impurities coming from the air can also be minimized by covering the trough or by carrying out

the experiments in a clean room. The subphase temperature can also be regulated with a

circulating water bath.










Once a Langmuir monolayer is formed at the A/W interface, a variety of surface pressure

related experiments are possible. The simplest experiment is the isotherm, where the monolayer

is compressed toward the center of the trough and the surface pressure recorded versus surface

density or mean molecular area (MMA, average area occupied by one molecule at the interface,

calculated from Equation 2-5).


M VA = "(2 -5 )


A is the area between the barriers, Mn is the molecular weight of the sample, NA is the

Avogadro' s number, and C and V are the concentration and the volume of the spreading solution,

respectively. Upon compression, the adsorbed molecules move closer to one another, the surface

pressure increases, and the phase transitions taking place in the monolayer are characterized by

pseudoplateaus or inflection points in the surface pressure versus MMA (or surface density)

isothermal plot as exemplified in Figure 2-3 for small amphiphilic molecules. The monolayer

undergoes phase transitions from the gaseous state (G) to the liquid state (L) and eventually to

the solid state (S) upon high compression.








Liqu~id








0.20 0 23 Oy 50 10 0
a (nmw molcule*)

Figure 2-3. Schematic isotherm for small amphiphilic molecules.14









Other possible experiments include compression-expansion hysteresis, isobaric, or

isochoric experiments. In the hysteresis experiment, the barriers compress the monolayer up to a

target surface pressure (or target MMA) and expand several times. In the isobaric experiment,

the monolayer is compressed up to a desired surface pressure which is then kept constant by

small barriers adjustments, and the evolution of the MMA versus time is recorded. In the

isochoric experiment, the barriers are stopped after reaching the desired surface pressure (or

MMA), and the surface pressure evolution is subsequently recorded versus time. These last 3

experiments are usually used to investigate monolayer stability versus time or its formation

reversibility as further exemplified in Chapters 3, 4, and 5.

2.2 Langmuir-Blodgett Films and Atomic Force Microscopy

One of the interesting properties of the Langmuir trough is that it is easy to transfer a

Langmuir monolayer prepared at the A/W interface onto a solid substrate for further analysis.

The most common technique for monolayer transfer is done by vertically lifting a substrate into a

Langmuir monolayer compressed at the desired surface pressure which is kept constant by small

barrier adjustments (Figure 2-4). The resulting transferred film is called a Langmuir-Blodgett

(LB) monolayer. The substrate used in this dissertation is freshly cleaved hydrophilic mica

because it mimics the water subphase during transfer. It is also possible to prepare LB films

consisting of multilayers by successively transferring several monolayers. This technique

provides thin films of supramolecular assemblies with well-defined molecular arrangement,s

chemical composition, and thickness, and with fewer defects than if prepared directly from the

bulk.

The transfer ratio measures the degree of monolayer transfer. During LB monolayer

formation, part of the molecules initially adsorbed at the A/W interface are slowly transferred

onto the substrate, which results in a lower surface density in the Langmuir monolayer. To keep










the surface pressure constant during transfer (and therefore the surface density), the barriers have

to move closer together which therefore reduces the available area between them. The transfer

ratio can be subsequently directly calculated by dividing this decrease in surface area between

the barriers by the total surface area of the substrate. Transfer ratio values smaller or larger than

unity indicate that the packing of the transferred molecules is less or more dense than at the A/W

interface, respectively.


Substrate (mica)



Barrier Wilhelmy plate Barrier








Wate r




Figure 2-4. LB film transfer onto a hydrophilic mica substrate.

The experimental technique used in this dissertation to examine the morphology of the LB

films in Chapters 3, 4, and 5 is atomic force microscopy (AFM). This technique provides a

topographical map of the LB films by scanning their surfaces with a sharp tip attached at the end

of a flexible cantilever which is deflected as it moves up and down mountains and valleys. A

laser is reflected off the end of the cantilever, and the deflection (measured by a photodiode) is

converted into a topographical image with a resolution of 0.1 nm accuracy. Contact and non-

contact AFM modes were first designed, but while in the contact mode soft samples can be

distorted, in the non-contact mode the tip can easily become stuck in the water layer covering the









surface of samples exposed to the atmosphere. The AFM tapping mode used in this dissertation

overcomes these problems. The tip is vibrated with sufficient energy to overcome the surface

tension of the contaminant water layer, and this vibration also prevents frictional forces from

dragging the sample, which is crucial when working with soft polymeric samples. The tapping

mode electronic setup is shown in Figure 2-5. As scanning occurs in three dimensions, the

scanner tube contains three piezo electrodes (a piezoelectric material is a substance that

proportionally contracts and expands depending on an applied voltage) for the X, Y, and Z

directions. In addition to its convenience in characterizing LB monolayers, AFM was also used

to image the molecularly imprinted nanoparticles after their deposition onto mica substrates as

further described in Chapter 7.

Fe~edr bac op Mai~bntalins
Constant Oscilledon1 Am1Splbituve! NlanoScope Illa
SController
Electron nics

eaFI I







Def~ctor
Electronice




ai I
Split Cantl~ever & Tip
Phlodrladle~b





Figure 2-5. The AFM tapping mode electronic setup.89








2.3 Transmission Electron Microscopy and Quasi-Elastic Light Scattering

Transmission electron microscopy (TEM) and quasi-elastic light scattering (QELS) were

used in Chapters 6 and 7 to determine the shape and size of the core-shell nanocapsules and of

the molecularly imprinted nanoparticles.

Electron microscopes use a beam of highly energetic electrons to examine objects on a

very fine scale and can yield information such as sample topography, morphology, composition,

or crystallinity.90 The electron source first forms a beam of electrons that are accelerated toward

the specimen with a positive electrical potential. The beam is focused onto the sample, and

various interactions can occur inside the irradiated sample, affecting the electron beam as shown

in Figure 2-6.


es~Cenc


X-~ca


I`
Un~wttered


Figure 2-6. Specimen interactions in electron microscopy.'"
The electrons of interest in TEM are only the unscattered electrons, even though the other

types of electrons can be of interest for other applications. These unscattered electrons are


Incklant le Beam
SBacksicattered &~



Ysi Ft hocdialuml


Irtcla~e~ealry









transmitted through the thin sample without any interaction occurring inside the sample. The

thicker areas will have fewer transmitted unscattered electrons and will therefore appear darker

than the thinner areas. The unscattered electrons strike a screen where light is generated,

allowing the user to see the sample image. Staining agents such as osmium tetroxide, ruthenium

tetroxide, or uranyl acetate can also be used to increase the contrast of thin samples that do not

sufficiently scatter the electron beam.

Quasi elastic light scattering (QELS, also called dynamic light scattering, DLS) is used to

determine the hydrodynamic radius or diameter of nano-sized particles suspended in a solution.

These particles are subject to Brownian motion, with small particles diffusing faster than large

particles according to the Stokes-Einstein equation (2-6) relating diffusion coefficient (D) and

particle radius (R):

k,T
D = (2-6)
6zy~rR

where kB is the Boltzmann constant, Tis the temperature, and rl is the solution viscosity. A beam

of laser light is first focused on the sample, the particles scatter the incoming light in all

directions, and the scattered photons are measured by a photomultiplier tube. The time variation

of the scattered intensity is then analyzed with a digital correlator used to compute the following

autocorrelation function C(r):

C(r) = Ae-2r "+ B (2-7)

where A and B are instrumental constants. The diffusion coefficient D is then determined from

the following 2 equations:


4mizsin( )
q = (2-8)










D~r (2-9)



where q is the scattering vector, n is the refracting index, 0 is the scattering angle, Ai is the laser

wavelength, and the particle hydrodynamic radius R is calculated from Equation 2-6. Each

monodisperse population of particle sizes produces its own unique autocorrelation function

(exponential decay). Mixtures of more than one size population produce sums of exponentials,

and therefore available algorithms can be used to extract "true" size distributions from complex

samp es.g

2.4 Cyclic Voltammetry

Cyclic voltammetry was used in Chapter 6 to monitor the uptake versus time of

hydrophobic electrochemical probes inside the oil-core of the core-shell nanocapsules. In cyclic

voltammetry, the potential of a working electrode is continuously changed as a linear function of

time, with the rate of change of potential referred to as the scan rate. The potential is first

scanned in one direction and then reversed at the end of the first scan. The advantage of such a

technique in electrochemistry is that the product of the electron transfer that occurred in the

forward scan can be probed again in the reverse scan. Figure 2-7 shows the basic shape of the

current response for a cyclic voltammetry experiment. The bulk solution first contains only the

reduced form of the redox couple, so for potentials (in A) lower than the redox potential, there is

no net conversion of the reduced form into the oxidized form. As the potential is increased

toward the redox potential, a net anodic current appears and increases exponentially. As the

reduced form is oxidized, concentration gradients appear, and diffusion occurs down these

gradients. At point B anodicc peak) and beyond, the potential is sufficiently high so the reduced

species reaching the electrode are immediately oxidized, and the current therefore now depends

upon the rate of mass transfer which results in an asymmetric peak shape. In C, the potential is


































200 400
Potential (mV)


D


reversed (decreased), and the current continues to decay. As the redox potential is approached, a

net reduction of the oxidized species takes place resulting in the appearance of a peak-shaped

cathodic current (D).


I



r,


600


Figure 2-7. Basic shape of the current response for a cyclic voltammetry experiment.92

In the presence of a reversible redox system, that is for fast electron transfer processes at

the electrode (reaction kinetics fast compared to the scan rate), the surface concentrations of the

oxidized and the reduced species are maintained at the values required by the Nernst equation (2-

10):


RT C,
E = E" + -In( )
nF CT


(2-10)


where E is the electrode potential, Eo is the standard potential of the redox couple, R is the

universal gas constant (8.314510 J K^1 mol- ), T is the temperature in K, n is the number of

electrons transferred in the half reaction, F is the Faraday constant (9.6485309x104 C mOl-1), and


-10 08









Co and C, represent the surface concentrations of the oxidized and reduced species, respectively.

The peak potential separation (Epa-Epc) is equal to 57/n, the peak width is equal to 28.5/n, the

peak current ratio (Ipa/Ipc) is equal to unity, and finally the faradaic current (Ip) is given by the

following Randles-Sevcik equation (2-11):

Ip = 2.69 x105 n3/2AD1/2 1/2C' (2-1 1)

where A is the electrode area (cm2), D is the diffusion coefficient of the electroactive species

(cm2/S), V is the scan rate (V/s), and C is the bulk concentration of the electroactive species

(mol/cm3). If A and vare kept constant during successive cyclic voltammetry scans, a decrease in

the bulk concentration of the electroactive species can be simply measured by monitoring the

decrease in the Faradaic current Ip. This strategy was applied as further discussed in Chapter 6 to

measure the encapsulation abilities and kinetics of two electrochemical probes with reversible

electrochemical activities (ferrocene methanol and ferrocene dimethanol) inside the oil core-

silica shell nanocapsules.









CHAPTER 3
POLYSTYRENE-b-POLY(TERT-BUTYLACRYLATE) AND POLYSTYRENE-b-
POLY(ACRYLIC ACID) DENDRIMER-LIKE COPOLYMERS: TWO-DIMENSIONAL
SELF-ASSEMBLY AT THE AIR-WATER INTERFACE

3.1 Introduction

As introduced in Chapter 1, block copolymers are of great interest for nanotechnological

applications because of their potential in forming well-defined morphologies in bulk,93 in

solution,94 Or at interfaces.95 Amphiphilic block copolymers offer good opportunities to control

interfacial properties, and since they self-assemble at hydrophilic/hydrophobic environments

such as the air/water (A/W) interface to form regular arrangements of two-dimensional surface

micelles, they are particularly interesting as precursors for the synthesis of well-defined patterns

with feature sizes typically in the nanometer scale order. The nanosized structures can be easily

controlled by varying various parameters such as the nature of the blocks, the molecular weight,

the relative lengths of the blocks, or even the block copolymer architecture. With a view toward

understanding the relationships between polymer architecture and A/W interfacial aggregation, a

variety of polystyrene-b-poly(ethylene oxide) block copolymers with simple and complex

architectures (linear, star-shaped, mikto-arm, dendrimer-like...) has been synthesized and

extensively investigated in the past few years.22,96

Concerning polystyrene-b-poly(tert-butylacrylate) (PS-b-PtBA) and polystyrene-b-

poly(acrylic acid) (PS-b-PAA) block copolymers, only little work has been reported on their

A/W interfacial behavior. Lennox and co-workers were to our knowledge the only ones to report

on the two-dimensional surface micelle formation for PS-b-PtBA block copolymers,

investigating linear samples with relatively small PtBA chains compared to the PS block.24,97 The

self-assembly of PS-b-PAA block copolymers was also studied almost exclusively for linear

samples,20,98 and it is only very recently that Tsukruk and co-workers described the self-assembly









of a twelve-arm heteroarm star copolymer with alternating PS and PAA arms at the A/W

interface.99 In a recent publication, we described the synthesis of a variety of dendrimer-like

copolymers based on polystyrene and poly(tert-butylacrylate) or poly(acrylic acid), and a

preliminary investigation of their surface properties confirmed that such systems are ideal

candidates for the synthesis of Langmuir and Langmuir-Blodgett (LB) monolayers with well-

defined morphologies.100

In this chapter, we study the A/W interfacial behavior of two dendrimer-like copolymers

composed of an eight-arm star polystyrene core with a sixteen-arm poly(tert-butylacrylate) or

poly(acrylic acid) corona (Figure 3-1) by surface pressure measurements isothermss, isochores,

and compression-expansion hysteresis experiments) and atomic force microscopy (AFM)

imaging. Among the different dendrimer-like copolymer samples previously synthesized, we

deliberately chose to focus here on these 2 samples since they have the largest number of arms

and the largest PtBA (or PAA) weight %. These polymers are significantly different from the

block copolymers studied in the previous literature in terms of architecture and chain length

ratio, which should therefore lead to an interesting and peculiar interfacial behavior.


PB n

S callx[8arene ore

S branchinrg pointP~~

polysyrn e o

polyver-butylacrylate~)

or porly~crlic cd


Figure 3-1. Schematic sketch of the PS-b-PtBA (Dendl) and the PS-b-PAA (Dend2) samples.









3.2 Results and Discussion

3.2.1 PS-b-PtBA Dendrimer-Like Copolymer (Dendl)

The isotherm of Dend1 is presented in Figure 3-2, and the inset shows the static elastic

modulus plot (e,, Equation 3-1) versus surface pressure.101

d (7)


The surface pressure in the isotherm increases in the high MMA region with a behavior

characteristic of liquid expanded and liquid condensed phases until a plateau suggesting a

biphasic state is observed at 24 mN/m. Upon further compression in the low MMA region, the

pressure sharply increases up to values as high as 70 mN/m. PS and PtBA are two hydrophobic

polymers, but contrary to PS, the presence of slightly polar ester groups in PtBA allows the

adsorption of PtBA homopolymers and PtBA-based block copolymers at the A/W interface. The

isotherm of Dend1 is very similar in shape to the isotherms of PtBA homopolymers, with only

one phase transition observed at 24 mN/m.102 Moreover, the extrapolation of the linear portion of

the isotherm below the plateau to zero pressure (Apancake 103 yields a value of 29 A+2 per PtBA

repeat unit, which is in good agreement with the previously reported literature.104 These two

observations indicate that Dend1 behaves similarly in terms of surface activity to PtBA

homopolymers, with the PS blocks desorbed in the air on top of the adsorbed PtBA blocks.

Nevertheless, these results are significantly different from those obtained by Lennox and co-

workers for linear PS-b-PtBA diblock copolymers with relatively low PtBA wt %.24,97 They

showed that the presence of the PS block induced two additional phase transitions of the PtBA

block below 20 mN/m and suggested that these transitions might originate from the peculiar

surface aggregation into circular micelles. As shown in the inset of Figure 3-2, only one local

minimum characteristic of a phase transition is observed at 24 mN/m for the static elastic









modulus versus surface pressure plot. Moreover, Dend1 also aggregates into spherical surface

micelles (Figure 3-3). This indicates that in the case of circular surface micelles, the extra phase

transitions are observable only for small PtBA chain length over PS chain length ratios (high PS

wt %). In the case of Dend1, we believe these transitions might be present but cannot be detected

since they involve only the small amount of PtBA repeat units present in the vicinity of the PS

micellar core, with the maj ority of the PtBA repeat units being too far and behaving similarly as

in PtBA homopolymers.


80
90




O 25 50 7

20 -1






0 25000 50000 75000 100000



Figure 3-2. Isotherm of Dend1. (Inset) Static elastic modulus plot versus surface pressure.

The AFM images of the LB films transferred below the plateau at 5, 10, 15, and 20 mN/m

(Figures 3-3a, 3-3b, 3-3c, and 3-3d) show the circular micellar aggregation of Dend1 mentioned

before with the bright circular domains corresponding to the desorbed PS cores (~ 1-1.5 nm

thick) and the darker background corresponding to the adsorbed PtBA chains. Estimation of the

number of Dend1 molecules per circular micelle by the total area method'os yielded an average









aggregation number of 3, independent of the surface pressure. PS has a high glass transition

temperature (Tg ~ 100 oC for high molecular weight PS),106 and therefore, once a surface micelle

has formed during the solvent spreading process, the micellar cores come closer to each other

during compression but the aggregation number remains unchanged with the chains stuck within

a particular micelle (the temperature of the experiment is well below the Tg of the desorbed PS

cores). Compression-expansion hysteresis experiments were carried out with target surface

pressures below the plateau and all the compression and expansion curves overlapped, which is

indicative of film formation reproducibility and thermodynamic stability. AFM imaging of the

LB films prepared during the second compression step of the hysteresis experiment did not

reveal any significant difference compared to the LB films formed during the first compression.

The aggregation number is much smaller than the value of 95 block copolymers per circular

surface micelle reported by Lennox and co-workers for a linear PS305-b-PtBA222 diblock

copolymer,97 which was expected based on the previous studies investigating the relationship

between aggregation number and block copolymer architecture. For instance, increasing the wt

% of the adsorbed PEO segment in linear PS-b-PEO diblock copolymers resulted in a lower

aggregation number.96c Even lower aggregation numbers were observed for PS-b-PEO three-arm

stars with a PEO corona compared to the linear analogues or compared to the reverse star

architecture with a PS corona.22 Similarly to these examples, the adsorbed PtBA chains of Dend1

are present in the corona and are approximately 10 times longer than the desorbed PS chains.

Moreover, the large number of arms connected to the central calix[8]arene core and the

dendrimer-like structure with 2 PtBA chains attached at the end of each PS arm also heavily

favor the formation of highly curved interfaces,96f therefore also considerably reducing the

aggregation number.













1 nmp







5 nmp

0 nm no i



Figure 3-3. Topographic AFM images ofDendl LB films transferred at 5 (a), 10 (b), 15 (c), 20
(d), 24 (middle of plateau, MMA = 20,000 A+2, e and f), and 40 mN/m (g and h).

A LB film of Dend1 was also transferred in the middle of the plateau (MMA = 20,000 A+2,

and the resulting AFM images are shown in Figures 3-3e and 3-3f. In this case, no transfer ratio

could be calculated since the barriers were manually stopped after compression before transfer,

and therefore these two AFM images only qualitatively reflect the A/W interfacial aggregation.

Nevertheless, the images clearly confirm the biphasic state of the plateau, with areas exhibiting

circular surface micelles similarly as for lower pressures and other areas with aggregated

domains significantly thicker (~ 3 nm) than the PS micellar cores. It was previously suggested

that at the beginning of the plateau region, the tert-butyl groups reorient from prone to vertical,

with further compression leading to film collapse.10 Since PtBA is a hydrophobic polymer, it

collapses by aggregating on top of the water surface. The aggregated areas observed in Figures

3-3e and 3-3f therefore likely correspond to desorbed Dend1 mono or multilayers. Compression-

expansion hysteresis experiments (3 cycles) were carried out in the plateau region, and the

resulting curves are shown in Figure 3-4. All the compression curves closely overlapped,

indicating that the collapsed films are able to go back to their original adsorbed monolayer state










upon barrier expansion. AFM imaging of the LB films transferred during the second

compression at a surface pressure of 20 mN/m confirmed the presence of adsorbed and circular

surface micelles and the absence of collapsed domains. Nevertheless, a drop in pressure is

observed during barrier expansion. Faster barrier speeds increased the pressure drop, which

suggests that the readsorption kinetics of the collapsed PtBA segments are slower than the barrier

expansion speed.

30

Compression

20 -2
Expansion






O 25000 50000 75000 100000
MMA (A2

Figure 3-4. Compression-expansion hysteresis plot of Dend1 (target MMA = 20,000 A+2.

Further compression in the low MMA region leads to a sharp surface pressure increase.

The films formed in this region of the isotherm should be unstable since the surface pressure is

higher than the PtBA collapse pressure of 24 mN/m. This was checked by carrying out isochoric

experiments. A typical isochore after compression up to 40 mN/m is shown in Figure 3-5. The

surface pressure undergoes a sudden drop within the first seconds of the experiment before

leveling off after a few minutes around 24 mN/m. It is not clear to us whether the sharp surface

pressure increase upon high compression in the isotherm originates from interactions between

the collapsed and desorbed aggregates formed in the plateau region or between eventual

remaining adsorbed PtBA segments. In any case, the isochoric experiments confirmed that the










films formed above the plateau are not thermodynamically stable and relax within minutes down

to the plateau surface pressure of 24 mN/m, which can be also seen as the equilibrium spreading

pressure of the PtBA blocks. Compression-expansion hysteresis experiments (3 cycles) were also

carried out in this high surface pressure region, and an example for a target pressure of 40 mN/m

is shown in Figure 3-6. The results are essentially similar to the hysteresis experiments carried

out in the middle of the plateau, with the compression curves overlapping each other, and the

expansion curves exhibiting a drop in pressure that corresponds to the slow readsorption of the

collapsed PtBA chains. AFM imaging of the LB films transferred during the second compression

at a surface pressure of 20 mN/m also confirmed here the presence of circular surface micelles

only. The morphology of the LB film transferred at 40 mN/m is shown in Figures 3-3g and 3-3h,

and aggregated domains in addition to the circular surface micelles are observed similarly as

within the plateau. Nevertheless, the transfer ratio was in this case significantly smaller than one

(~ 0.25), which indicates that the film underwent non-negligible expansion during transfer,

suggesting that the density of desorbed aggregates on the water surface is significantly greater

than as shown in Figures 3-3g and 3-3h.

40


35





25


20
O 10 20 30
Time (min)

Figure 3-5. Surface pressure/time isochoric relaxation plot of Dend1 after compression up to 40
mN/m.









50

40-

30 impression

S20-

10- Expansion



0 25000 50000 75000 100000

MMA (a2)

Figure 3-6. Compression-expansion hysteresis plot of Dend1 (target pressure = 40 mN/m).


3.2.2 PS-b-PAA Dendrimer-Like Copolymer (Dend2)

As a preliminary study, we investigated the behavior of a PAA homopolymer (PAA250K>,

since to our knowledge no information is available in the previous literature on the Langmuir and

LB monolayers of PAA homopolymers. PAA250K COuld not be dissolved in chloroform, so a

chloroform/ethanol mixture (1/2 in volume) was used instead as the spreading solvent. PAA is a

weak acid (pKa ~ 5.5),'0s and its degree of ionization and consequently its surface activity are

therefore strongly pH dependent. Under basic conditions (pH = 11i), the acid groups of PAA are

deprotonated, and stable Langmuir monolayers of PAA250K COuld not be prepared, with the

surface pressure remaining close to 0 mN/m during barrier compression. When ionized, PAA is

not surface activel09 and irreversibly dissolves into the aqueous subphase. Under acidic

conditions (pH = 2.5), the acid groups of PAA are protonated, the chains become less

hydrophilic and surface active, and therefore stable Langmuir monolayers of PAA250K COuld now

be prepared. The resulting isotherm is shown in Figure 3-7. The surface pressure slowly

increases in the high MMA region before a plateau is reached with the surface pressure leveling









off around 3.5 mN/m. In the high MMA region, the surface pressure increases with a behavior

characteristic of liquid expanded and liquid condensed phases, and PAA250K is likely adsorbed in

a pancake conformation. The AFM image shown in Figure 3-8a (7<= 1.5 mN/m) confirmed the

presence of a pretty homogeneous PAA250K LB film with the randomly distributed darker holes

possibly forming after transfer as the PAA chains un-swell (dehydrate) during the drying step.

PAA in its protonated form is surface active but it is still highly water soluble, and it has been

previously shown for aqueous solutions of protonated PAA that the surface pressure reaches a

maximum, for instance around 3 mN/m for a molecular weight similar to PAA250K.109a This value

correlates well with the plateau surface pressure, which indicates that, at this pressure, PAA250K

desorbs from the interface and aggregates inside the water subphase. The AFM images obtained

for the LB films transferred at 3 and 3.5 mN/m are shown in Figures 3-8b and 3-8c, respectively.

As the films are compressed within the plateau region, more and more desorbed aggregates (~ 3-

5 nm thick) are observed. This indicates that when the PAA chains collapse by dissolving into

the water subphase, they stay in the vicinity of the interface, probably remaining anchored by

some adsorbed acrylic acid repeat units that have not collapsed yet.














0 50000 100000 150000 200000
MMA (A~2)

Figure 3-7. Isotherm of PAA250K (pH = 2.5).











2 nm


11nm 10 ~ nm e e
0 nm m 0nm



Figure 3-8. Topographic AFM images of PAA250K LB films transferred at 1.5 (a), 3 (b), and 3.5
mN/m (c).

The spreading solutions of Dend2 were prepared by using the same solvent mixture as for

PAA250K (chloroform/ethanol mixture, 1/2 in volume). Similarly as for PAA250K, HO stable

Langmuir monolayers could be formed for Dend2 under basic conditions with its irreversible

dissolution in the aqueous subphase. Contrary to the other PS-b-PAA systems reported in the

previous literature,20,98,99 the PS wt % in Dend2 is too low to allow it to act as an anchor and thus

preventing the dendrimer-like aqueous dissolution. Nevertheless, under acidic conditions (pH =

2.5), the PAA segments of Dend2 are now protonated, and, similarly as for PAA250K, Dend2

becomes surface active. The resulting isotherm is shown in Figure 3-9, and the inset shows the

monolayer compressibility plot (K, Equation 3-2) versus surface pressure.96

1 1 d (NLVA )
K= (3-2)
E, MVIA d(Fir)

In the high MMA region, the surface pressure slowly increases before reaching a pseudoplateau

around 5 mN/m (maximum in monolayer compressibility as seen in the inset of Figure 3-9) and

sharply increasing under high compression up to approximately 10 mN/m. A pseudoplateau was

already observed in the previous literature by Currie et al. only for long PAA chains in linear PS-

b-PAA systems under acidic conditions, where they demonstrated by surface pressure and

ellipsometry measurements the presence of a pancake-to-brush transition in the pseudoplateau








region with the PAA segments dissolving into the water subphase.20 It is not very clear at this

point why the pseudoplateau surface pressure is a little bit higher for Dend2 (5 mN/m) compared

to the PS-b-PAA copolymers studied by Currie et al. or compared to PAA250K (3-4 mN/m). It

might simply be a PAA chain length dependence, or possibly a peculiar influence of the
dendrimer-like architecture.


0.7

8 0.5-





4- 2 4 6 8
~t ~Ix (mN/m)





0 25000 50000 75000 100000

MMA (iM)

Figure 3-9. Isotherm of Dend2 (pH = 2.5). (Inset) Compressibility plot versus surface pressure.
We investigated here the morphological evolution by AFM imaging as the Langmuir films

of Dend2 are compressed, and the resulting images of the LB films are shown in Figure 3-10. At

low surface pressure (7< = 2 mN/m, Figure 3-10a), Dend2 aggregates into spherical surface

micelles with bright PS cores (~ 1 nm thick) and a darker background corresponding to the PAA

blocks adsorbed in a pancake conformation similarly as in Figure 3-8a for PAA250K. The average

aggregation number was estimated around 5 by the total area method.'os Such a low value can be









rationalized similarly as for Dend1, with the long PAA chains present in the corona, the

dendrimer-like shape, and the large number of arms emanating from the central calix[8]arene

core all heavily favoring the formation of highly curved interfaces. The images shown in Eigures

3-10b through 3-10j were recorded for surface pressures within the pseudoplateau and ranging

from 4 to 8 mN/m. As the fi1ms are compressed, the PAA segments progressively dissolve in the

aqueous subphase, underneath the PS cores of the surface micelles that aggregate into larger and

thicker (~ 2 nm) domains. At the end of the pseudoplateau, in the region where the surface

pressure sharply increases under high monolayer compression (7[= 8 mN/m, Figures 3-10k and

3-101), all the PAA chains have desorbed in the water subphase and stretch to form a brush

underneath the aggregated PS cores. Contrary to the hydrophobic PtBA segments of Dend1 that

collapsed above the A/W interface, the hydrophilic PAA segments of Dend2 anchored by the PS

segments dissolve into the water subphase. Compression-expansion hysteresis experiments were

also conducted within the pseudoplateau region (target pressure = 5 mN/m), and the results are

presented in Figure 3-11. Very little hysteresis is observed with the pseudoplateau still present

after numerous cycles, which means that the desorbed PAA segments can return to their original

adsorbed state at low pressure after monolayer decompression. This was verified by transferring

a LB fi1m at 2 mN/m during the second compression cycle, and AFM imaging revealed the

presence of circular surface micelles with no aggregated domains. We do not have yet at this

point enough experimental evidence to rationalize the small hysteresis shift, but it could for

instance come from some entanglement of the PAA chains during the pancake-to-brush

transition or from a different arrangement of the expanded PAA chains in terms of hydration and

conformation compared to the one adopted after spreading and before the first compression.110














5 nm

2.5 nm

0 nm


Figure 3-10. Topographic AFM images of Dend2 LB films transferred at 2 (a), 4 (b), 4.5 (c and
d), 5 (e and f), 5.5 (g and h), 6 (i and j), and 8 mN/m (k and 1).


8






2

0


Figure 3-11. Compression-expansion hysteresis plot of Dend2 (target pressure = 5 mN/m, pH
2.5).


25000


50000
MMA (iM)


75000


100000









3.3 Conclusions

In this work, the A/W interfacial behavior of two dendrimer-like block copolymers based

on polystyrene and poly(tert-butylacrylate) (Dendl) or poly(acrylic acid) (Dend2) and their LB

film morphologies on hydrophilic mica substrates were investigated. Dend1 formed

thermodynamically stable Langmuir monolayers and self-assembled into circular surface

micelles up to 24 mN/m with a very low aggregation number (~ 3), likely resulting from the high

PtBA wt % and from the peculiar dendrimer-like architecture. At 24 mN/m, the PtBA segments

desorbed and aggregated on top of the water surface, and all the monolayers formed beyond this

threshold were metastable and relaxed down to 24 mN/m. Poly(acrylic acid) is surface active

only under acidic pH conditions below its pKa value (~ 5.5), and a preliminary study on a PAA

homopolymer (PAA250K, Mn = 250,000 g/mol) showed that it is able to form stable monolayers

up to ~ 3.5 mN/m before dissolving in the water subphase. Because of its small PS wt %, Dend2

similarly did not form stable Langmuir monolayers under high pH conditions, and therefore its

self-assembly at the A/W interface was investigated only under acidic conditions. The isotherm

indicated the presence of a pseudoplateau at 5 mN/m characteristic of a phase transition that

corresponds to a pancake-to-brush transition, with the progressive aqueous dissolution of the

PAA segments underneath the anchoring PS cores. For pressures below the pseudoplateau,

Dend2 molecules also aggregated into circular surface micelles with a very low aggregation

number (~ 5). This study confirmed that various parameters such as for instance polymer

architecture, chain length/polarity, surface density, or even subphase pH can all strongly

influence the self-assembly of block copolymers at the A/W interface. Therefore, while this

work gave some hint of the interesting interfacial properties of these two novel PS-b-PtBA and

PS-b-PAA dendrimer-like copolymers, additional investigations with other samples with









different numbers of arms and chain lengths are necessary for a better understanding of the

influence of the dendrimer-like structure.

3.4 Experimental Methods

3.4.1 Materials

The synthesis of the PS-b-PtBA (Dendl, 2s = 240,000 g/mol, PDI = 1.26) and PS-b-PAA

(Dend2, 2s = 139,000 g/mol, PDI = 1.28) dendrimer-like copolymers was realized according to

a previously reported procedure.100 These block copolymers consist of an eight-arm PS core (2\%,

= 10,000 g/mol, ~ 12 styrene units/arm) with a sixteen-arm PtBA (2, = 230,000 g/mol, ~ 112

tert-butylacrylate units/arm, PS wt % ~ 4 %) or PAA (2, = 129,000 g/mol, ~ 112 acrylic acid

units/arm, PS wt % ~ 7%) corona. The PAA homopolymer (PAA250K, 2Ms ~ 250,000 g/mol) was

purchased from Aldrich Chemical Co. and was used as received without further purification.

3.4.2 Langmuir Films

Surface pressure measurements were accomplished by use of a Teflon Langmuir trough

system (W= 160 mm, L = 650 mm, KSV Ltd., Finland) equipped with two moving barriers and a

Wilhelmy plate. The PS-b-PtBA dendrimer-like copolymer sample (Dendl) was prepared by

dissolving approximately 1 mg of polymer in 1 mL of chloroform. The PS-b-PAA dendrimer-

like copolymer (Dend2) and the PAA homopolymer (PAA250K) Samples were prepared by

dissolving approximately 1 mg of polymer in 1 mL of a chloroform/ethanol mixture (1/2 in

volume). Volumes ranging from 10 to 30 puL were spread dropwise with a gastight Hamilton

syringe on Millipore filtered water (subphase resistivity > 18.2 MGZ.cm) of the desired pH value,

and the spreading solvents were allowed to evaporate for 30 min. In all the experiments,

subphase temperature and barrier speed were kept constant at 25 OC and 5 mm/min, respectively.










3.4.3 AFM Imaging

The LB films were formed by transferring the Langmuir films of Dendl, Dend2, and

PAA250K Onto freshly cleaved mica at various surface pressures. The desired surface pressure

was attained at compression/expansion rates of +/-5 mm/min. Once the films had equilibrated at

a constant surface pressure for 15 min, the mica substrate was then pulled out of the water at a

rate of 1 mm/min. All the transfer ratios were close to unity unless otherwise stated, which is

indicative of successful transfer. The transferred films were air-dried in a desiccator for 24 h and

subsequently scanned in tapping mode with a Nanoscope III AFM (Digital Instruments, Inc.,

Santa Barbara, CA) using Nanosensors silicon probes (dimensions: T = 3.8-4.5 pum, W = 26-27

pum, L = 128 pum). All the images were processed with a second-order flattening routine.









CHAPTER 4
LANGMUIR AND LANGMUIR-BLODGETT FILMS OF POLY(ETHYLENE OXIDE)-b-
POLY(s-CAPROLACTONE) STAR-SHAPED AND LINEAR BLOCK COPOLYMERS

4.1 Introduction

Poly(s-caprolactone) (PCL) and poly(ethylene oxide) (PEO) are two biocompatible

polymers with PCL biodegradation leading to nontoxic products.111,112 Low molecular weight

PEO is not biodegradable but can be eliminated from the body by the renal system.113 The

introduction of a hydrophilic and highly flexible PEO block at the end of a PCL block allows the

potential to tailor PCL properties such as its high hydrophobicity, high crystallinity, and slow

biodegradation.114 Therefore, synthesis of PEO-b-PCL copolymers with various architectures has

resulted in a growing number of reports citing potential applications including drug delivery

systems, temporary bioabsorbable implants, and tissue engineering.112,1 15,116

The air/water (A/W) interface has received much attention to investigate the self-assembly

of various amphiphilic molecules because of its ability to mimic hydrophilic/hydrophobic

interfaces. When polymers having biological applications are considered, such as PEO and PCL,

the A/W interface is of particular interest because of its presence in many biological systems.

Both PEO and PCL homopolymers spontaneously adsorb at the A/W interface to form stable

monolayers in a moderate surface pressure range. PEO homopolymers have been extensively

studied in solutions and at interfaces, and it has been shown that PEO chains irreversibly dissolve

in the water subphase at relatively low surface pressures. Surprisingly, very little interest has

been put into fundamentally understanding the aggregation in Langmuir monolayers of PCL-

based block copolymers and PCL homopolymers. Leiva et al. were to our knowledge the first to

report on the A/W interfacial properties of PCL homopolymers, and they observed collapse

pressure values ranging from 13 to 20 mN/m depending on the molecular weight, and

aggregation of the hydrophobic PCL chains on top of the water surface after collapse." It is only









very recently that Esker and co-workers extensively studied PCL crystallization mechanism in

the collapse region by Brewster angle microscopy and isobaric area relaxation analyseS.101,119

The only example in the previous literature investigating the A/W self-assembly of PCL-based

block copolymers was reported by Lee et al. for an architecture with two linear PCL chains

anchored to a dendritic hydrophilic head.120

Chemically attaching a hydrophilic PEO block to a hydrophobic PCL block enhances the

amphiphilicity and the surface activity of the resulting block copolymer, allowing higher surface

pressures to be reached, as previously shown for other PEO-based amphiphilic block

copolymers.22,23 To our knowledge, no work has been reported on the A/W interfacial behavior

of block copolymers based on PEO and PCL. With a view toward guest encapsulation, we

recently reported the synthesi s of a seri es of poly(ethylene oxi de)-block-poly(s-caprol actone)

copolymers with star-shaped and linear architectures by ring-opening polymerization of e-

caprolactone at the end of hydroxyl-terminated star-shaped or linear PEO macroinitiators.121 In

the present chapter, we study the behavior of these samples as well as the corresponding PEO

and PCL homopolymers at the A/W interface (Langmuir monolayers) by surface pressure

measurements isothermss, compression-expansion hysteresis, and isobaric relaxation

experiments), and we employ AFM to characterize the Langmuir-Blodgett (LB) films'

morphologies after transfer onto hydrophilic mica substrates. The PEO-b-PCL five-arm stars

consist of a hydrophilic PEO core with 9 ethylene oxide units/arm with hydrophobic PCL chains

at the star periphery. Each star contains different amounts of PCL, varying from 0 to 18 e-

caprolactone units/arm (Figure 4-1 and Table 4-1). The linear PEO-b-PCL diblock copolymers

synthesized from a linear PEO macroinitiator (PEO2670, Mn = 2,670 g/mol, ~ 60 ethylene oxide

repeat units) contain different amounts of PCL, varying from 11 to 35 e-caprolactone repeat units










(Figure 4-2 and Table 4-2). The other PEO homopolymer PEO2000 (2r = 2,000 g/mol; PDI =

1.20) and the PCL homopolymers PCL1250 (2r = 1,250 g/mol; PDI = 1.50), PCL2000 (2r =

2,000 g/mol; PDI = 1.45), and PCL10000 (2r = 10,000 g/mol; PDI = 1.40) were commercially

available (purchased from Aldrich Chemical Co.) and were used as received without further

purification.

PEO core: n=9, m=0
H, Star#1: n=9, m=3 ,H
m /Yo_ Star#2: n=9, m=6 r m
Star#3: n=9, m=9
Star#4: n=9, m=12
oh c Star#5: n=9, m=15 ? 'o
Star#6: n=9, m=18

O O





9/ o



Hm


mH

Figure 4-1. The star-shaped PEO-b-PCL block copolymers.

Table 4-1. Characteristic values of the star-shaped polymers.

Name PO Star#1 Star#2 Star#3 Star#4 Star#5 Star#6
core

2Mn a (g/mol) 2, 150 4,200 6,370 8,200 9,630 11,220 13,110
PDIb 1.10 1.25 1.37 1.35 1.45 1.36 1.44

Avg no. of ethylene oxide
99 99 99 9
umits per arm
Avg no. of e-caprolactone 0369 1 51
umits per arm
a Determined by 1H NMR
b Determined by GPC calibrated with linear polystyrene standards.















n = 60, m = 0, 11, 19, 27 and 35

Figure 4-2. The linear PEO-b-PCL block copolymers.

Table 4-2. Characteristic values of the linear PEO macroinitiator and of the linear diblock
copolymers.
PEO60-b- PEO60-b- PEO60-b- PEO60-b-
Name PEO2670
PCL11 PCL19 PCL27 PCL35
M~n a (g/mol) 2,670 3,940 4,780 5,780 6,680
PDIa 1.05 1.10 1.13 1.11 1.24
Avg no. of ethylene
60 60 60 60 60
oxide units

Av n. f -0 11 19 27 3 5
caprolactone units
a Determined by GPC calibrated with linear poly(ethylene oxide) standards.

4.2 Results and Discussion

4.2.1 PEO Homopolymers

The isotherms of the five-arm PEO core for subphase pH values of 5.5 (Millipore filtered

water) and 13 (0.1 M NaOH) are presented in Figure 4-3. The isotherms of the linear PEO

homopolymers (PEO2000 and PEO2670) are also included. The inset shows the same isotherms

normalized with respect to the number of ethylene oxide repeat units. For PEO2000 and

PEO2670, the surface pressure increases until a pseudoplateau that corresponds to the

irreversible aqueous dissolution of the PEO chains is reached at 5 and 6.2 mN/m, respectively.

As previously described, Langmuir films of PEO homopolymers are thermodynamically stable

for low surface pressures."' Upon compression the monolayers collapse, and the water-soluble

PEO chains irreversibly dissolve in the water subphase for pressures that are molecular weight

dependent (maximum collapse pressure value ~ 10 mN/m for high molecular weight PEO).122









The behavior of the PEO core significantly differs from that of the linear analogue PEO2000. No

pseudoplateau is observed, and the pressure slightly increases only for high compression, as

indicated by the shift toward the low area per monomer region compared to PEO2000. The

Millipore water pH (5.5) is acidic enough to protonate the triamine present in the center of the

PEO core, therefore increasing its water solubility compared to the neutral form. To investigate

the pH influence on the surface activity of the PEO core, a control isotherm was carried out with

a subphase pH value of 13, where the triamine is no longer protonated. The isotherm shape was

very similar to that at pH = 5.5. A slightly increased pressure was obtained for high compression,

but no pseudoplateau was observed. The absence of a pseudoplateau and the small pressure

increase only for high compression indicate a negligible surface activity of the adsorbed

molecules and the presence of a nonstable film. This assumption was verified by carrying out

compression-expansion hysteresis experiments on the PEO core for a target pressure of 2 mN/m

(Figure 4-4). Successive compression/expansion curves shifted toward smaller mean molecular

areas, which is indicative of a loss of material in the aqueous subphase. The pressure increase is

thought to arise from a kinetic effect, where the barrier compression speed is faster than the

dissolution rate of the PEO core molecules into the aqueous subphase, leading to a metastable

monolayer. Compared to the linear analogue, the star-shaped PEO core not anchored to

hydrophobic chains has little or no surface activity at the A/W interface and is therefore

thermodynamically more stable being solvated in the aqueous subphase than being adsorbed at

the interface, independent of the surface pressure. This behavior can be related to the high

polarity (presence of five hydroxyl groups) and the compact architecture (star-shaped) of the

PEO core, which is therefore more likely to dissolve in the water subphase than the linear

analogue.








































. First compression
cI First expansion
o Second compression
* Second expansion


* PEO2000 2
a PEO core pHI=5.5 20


40 60
ylene
(M)"


20 -
~-oPEO core pH=1 3 15 -
~4 -s- PEO2670 10E~l
~15 -

E 0 20
10 Area per eth
~t oxide unit






0 500 1000 1500 2000
MMA (AZ2)

Figure 4-3. Isotherms of the PEO homopolymers. (Inset) Same
respect to the number of ethylene oxide units.


I


2500 3000



isotherms normalized with


300


600 900
MMA (AZ2)


1200


1500


Figure 4-4. Compression-expansion hysteresis plot of the PEO core (target pressure = 2 mN/m).









LB films of the PEO core could not be prepared because of its Langmuir monolayer

instability, so only PEO2000 and PEO2670 were transferred at 2 mN/m. PEO crystallization

from the bulk and organic solvents has been extensively investigated under various experimental

conditions including in thin films.123,124 The AFM scan of the PEO LB films indicated the

presence of a flat surface with no PEO crystals. PEO is highly hydrophilic, and previous studies

showed that every ethylene oxide unit can be hydrated with up to three water molecules.125

Recent studies in PEO-b-PCL systems indicated that hydrated PEO chains essentially lost their

ability to crystallize.126 The fact that we did not observe any crystallization in PEO2000 and

PEO2670 LB films probably arose from a similar situation where as the films dried, the PEO

chains remained highly hydrated and could not crystallize. PEO also has a high affinity for the

hydrophilic mica substrate, which can be another energy barrier preventing aggregation and

chain folding necessary for crystallization to take place.

4.2.2 PCL Homopolymers

While the main objective of our study was to gain a deeper understanding of the A/W

interfacial behavior of PEO- and PCL-based block copolymers, a preliminary study on PCL

homopolymers involving isothermal and compression/expansion hysteresis experiments with

experimental parameters (barrier speeds and target pressures) similar to the ones used for the

linear and star-shaped PEO-b-PCL samples needed to be done. The isotherms of the PCL

homopolymers introduced earlier are presented in Figure 4-5, with a log scale on the x-axis for

convenient visualization. The inset shows the same isotherms normalized with respect to the

number of e-caprolactone repeat units. At low pressures, the PCL chains are adsorbed at the

interface with a behavior characteristic of liquid expanded and liquid condensed phases. Below

the collapse pressure, theoretical investigations by Ivanova et al. showed that PCL chain packing









and orientation is probably surface pressure-dependent. 127 The inset shows that below the

collapse pressure, chain packing is not molecular weight-dependent. Compression-expansion

hysteresis cycles were performed in this surface pressure range and all the compression-

expansion curves closely overlapped, confirming the thermodynamic stability of the

monolayers.128,129

25:
S25
20





Area per e-caprolactone
10 unit (A~2)
*5-PCL1 250*
+ PC L2000)
51 *PCL10000*



10 100 1000 10000 100000

MMA (iM)

Figure 4-5. Isotherms of the PCL homopolymers. (Inset) Same isotherms normalized with
respect to the number of e-caprolactone units.

The collapse region of most amphiphilic molecules is more difficult to quantitatively

analyze because it is a thermodynamically unstable pressure region where various phenomena

such as desorption of molecules from the interface or local formation of multilayers can happen.

Many polymers show viscoelastic behavior in this region, leading to surface properties that are

barrier speed-dependent.130 As shown in Table 4-3, the collapse pressure (defined as the point

where a sudden change in slope is observed) is molecular weight-dependent, with the longer

PCL chains collapsing at lower pressures. PCL is a highly hydrophobic polymer, and its collapse









therefore results in the aggregation of the water-insoluble PCL chains on top of the aqueous

subphase. An interesting feature characteristic of PCL collapse is the obvious decrease in

pressure after the collapse point, a phenomenon that was attributed by Esker and co-workers to

PCL crystallization directly on the water surface. Longer PCL chains have increased

hydrophobicity and crystallinity compared to smaller PCL chains, which explains the lower

collapse pressure and increased pressure drop after the collapse point.

Table 4-3. Collapse pressure values of the PCL homopolymers.
Name PCL1250 PCL2000 PCL10000
Collapse pressure (mN/m) for
14.6 12.9 11.1
compression speed = 5 mm/min
Collapse pressure (mN/m) for
N/A 14.1 11.4
compression speed = 100 mm/min

Further evidence for PCL crystallization came from the isotherms recorded for a barrier

compression speed of 100 mm/min (Figure 4-6). The pressure decrease after the collapse point

almost completely vanishes, and as shown in Table 4-3 the collapse pressure increases. This

indicates that in this case the rate of crystallization is slow compared to the compression speed

and that the resulting monolayers are metastable in this pressure region. Thermodynamic

collapse pressure values could not be easily obtained experimentally with our equipment because

it would require infinitely slow compressions. The collapse pressure for PCL1250 (100 mm/min)

could not be accurately determined because its isotherm does not show a clear collapse, but the

shallower turning point between 12 and 15 mN/m can nevertheless be attributed to the collapse

"point" of this film.












20 -( *PCL1250

`9 PCL2000
ti15 -



5 o

I~ lo



10 100 1000 10000 100000
MMA (M)

Figure 4-6. Isotherms of the PCL homopolymers (compression speed = 100 mm/min).

Compression-expansion hysteresis cycles were also carried out beyond the collapse point.

Figure 4-7 shows the compression-expansion hysteresis experiment carried out for PCL1250.

The first compression is similar to the isotherm reported in Figure 4-5. As the film is expanded,

the pressure suddenly drops until an expansion pseudoplateau appears at a pressure significantly

lower than the collapse pressure during compression. This expansion pseudoplateau corresponds

to the readsorption/melting of the PCL chains that had previously crystallized. This

pseudoplateau pressure is molecular weight-dependent, with the smaller PCL chains readsorbing

at higher pressure (10, 8, and 4 mN/m for PCL1250, PCL2000, and PCL10000, respectively).

The compression curve of the second cycle is slightly shifted toward smaller areas, and a

decrease is observed for the collapse pressure. This phenomenon is the result of residual PCL

crystals that remained on the water surface from the initial monolayer compression and that act

as nucleation sites for the crystallization of the other adsorbed PCL chainS.101,119 Further










compression-expansion cycles essentially overlapped the second cycle with no noticeable

pressure changes concerning the collapse or the expansion pseudoplateau.

25


20
SFirst compression
I ci First expansion
S15 .o Second and third compressions
Z Second and third expansions

S10







0 200 400 600 800
MMA (lj)

Figure 4-7. Compression-expansion hysteresis plot of PCL1250.

Typical AFM images of the PCL homopolymers LB films transferred below monolayer

collapse (7<= 7 mN/m), before crystallization on the water surface takes place, are shown in

Figure 4-8a and 4-8d. Surprisingly, PCL crystals could be observed. According to the isotherms

that are characteristic of liquid condensed phases in this low surface pressure range, the PCL

homopolymers are transferred into smooth and hydrated monolayers adsorbed onto the mica

surface. We believe that upon drying, during and after transfer, part of the PCL chains leave the

surface and crystallize, which likely results in a mica surface only partially covered with

adsorbed or crystallized PCL chains. For comparison, PCL homopolymers were also transferred

beyond monolayer collapse, after crystallization on the water surface takes place (Figure 4-8b, 4-

8c, and 4-8e). The transfer ratios were in this case significantly greater than 1 (~ 2-3), which was

predictable since crystallization and therefore intrinsic MMA decrease take place over time in









this surface pressure range. PCL crystals were also observable, with spherulitic architectures

significantly different from those obtained by Esker and co-workers directly at the A/W interface

using BAM.101,119 This suggests that the AFM images recorded above monolayer collapse are not

only the result of PCL crystallization at the A/W interface but also the result of additional PCL

crystallization taking place during and after transfer. By use of cross-section analysis (Figure 4-

8f), all the PCL crystals were determined to be approximately 7.5 nm thick, which is consistent

with the previously reported literature on PCL lamellae thickness.131 The thickness was

independent of PCL molecular weight, which indicates that the chains stretch perpendicular to

the surface and fold every 7.5 nm, with the crystals probably growing parallel to the surface.

Nevertheless, further comparison between PCL crystallization in LB films and the previously

reported work on PCL crystallization in bulk,132 fTOm an organic solution,133 Or even in thin

filmsl34-136 remains difficult to make because different types of variables are involved.



20 nm

10 nm

0 nm








7.5 nm





Figure 4-8. Topographic AFM images of PCL homopolymers LB films transferred below and
above monolayer collapse: PCL2000 at 7 (a) and 13 mN/m (b and c), and PCL10000
at 7 (d) and 11.2 mN/m (e). (f) Cross-section analysis performed at the edge of a
PCL2000 crystal.









4.2.3 Star-Shaped PEO-b-PCL Block Copolymers

The isotherms of the PEO-b-PCL five-arm stars are presented in Figure 4-9. They exhibit

essentially three different regions that can be attributed to different conformations of the polymer

chains. In the high MMA region, the surface pressure slowly increases as the films are

compressed until a pseudoplateau is reached for intermediate mean molecular areas. As the

compression continues in the low MMA region, the surface pressure sharply increases, reaching

elevated surface pressure values and highly compressed films.

40

.Star#6
30
0 Star#5
lit I* Star#4
20 Star#3
i'Star#2
10~I -+Star#1



0 3000 6000 9000 12000 15000
MMA (Ajz)

Figure 4-9. Isotherms of the star-shaped PEO-b-PCL copolymers.

4.2.3.1 High MMA region

The first step toward understanding the behavior of the stars in this region was to check

monolayer formation reversibility and stability. This was done by carrying out compression-

expansion hysteresis experiments with target pressures up to 9 mN/m. For Star#6, Star#5, Star#4,

and Star#3, all the compression and expansion curves are superimposable independent of the

target pressure, which is indicative of film formation reproducibility and stability. These four

stars have the largest PCL amounts and are therefore hydrophobic enough so the amount of































2 compressions


2 expansions


material adsorbed at the interface remains constant over time, without irreversible dissolution in

the aqueous subphase (Figure 4-10). As the PCL content is decreased, monolayer stability is

reduced. For Star#2, the compression-expansion cycles start shifting toward smaller mean

molecular areas, and this shift is even more pronounced for Star#1 (Figure 4-11). For these two

samples, the small PCL chains are insufficient to overcome the overall star hydrophilicity arising

from the water-soluble PEO core, and irreversible water dissolution takes place over time.


25


20



5-



10


000 10000


'12000


Figure 4-10. Compression-expansion hysteresis plot of Star#6 (target pressure = 9 mN/m).

25


20
h First compression
15 -I c First expansion
a Second compression
*Second expansion







0 1000 2000 3000 4000
MMA (AZ)

Figure 4-11. Compression-expansion hysteresis plot of Star#1 (target pressure = 9 mN/m).


0 2000 4000 6000 8(
MMA (iA2)









From the initial study on the homopolymers, it was shown that in the low pressure region

e-caprolactone repeat units are adsorbed at the A/W interface independent of the molecular

weight and that the PEO core alone has limited surface activity which leads to its irreversible

dissolution in the aqueous subphase. For the star-shaped block copolymers, the interfacial

behavior of the PEO core might be significantly changed as it is chemically attached to

hydrophobic PCL chains. To estimate the interfacial area occupied by the PEO core of the star-

shaped block copolymers, only the isotherms of Star#6, Star#5, Star#4, and Star#3 were used, as

the corresponding Langmuir monolayers are thermodynamically stable below the pseudoplateau.

For target pressures ranging from 1 to 11 mN/m, the MMA was plotted versus the number of e-

caprolactone repeat units as shown in Figure 4-12. The resulting curves were analyzed by linear

regression leading to R2 ValUeS greater than 0.99. The linear relationships indicate that the

adsorption of the PCL blocks is not molecular weight-dependent as it is for linear PCL

homopolymers. More interestingly, the y-axis intercepts are significantly different from zero,

indicating the non-negligible interfacial area occupied by the PEO core anchored by the PCL

chains. The surface pressure was then plotted versus the y-axis intercept values to give the

extrapolated isotherm of the PEO core of the block copolymers (Figure 4-13). The experimental

PEO2000 isotherm was also included for comparison. Both curves have been normalized with

respect to the number of ethylene oxide units. For low surface pressures (x < 4 mN/m), the

experimental PEO2000 and the extrapolated PEO core isotherms overlap reasonably, indicating a

similar interfacial area occupied by an ethylene oxide repeat unit of the PEO core compared to

the linear PEO analogue. The two curves stop overlapping above 4 mN/m because PEO2000 is

irreversibly dissolved in the aqueous subphase. It is also very interesting to notice in the

isotherms of the block copolymers, for surface pressures lower than 11 mN/m, the absence of











pseudoplateaus or inflection points characteristic of PEO aqueous dissolution. This absence is

also shown in the compressibility plot K versus surface pressure (Figure 4-14), where no peak


(local maximum) is observed below 11 mN/m (in compressibility plots versus surface pressure,

every phase transition in a Langmuir monolayer results in a local compressibility maximum).

This suggests that the PEO core of the star-shaped block copolymers is probably not adsorbed at

the interface but more likely already solvated in the water subphase in the vicinity of the

interface.

9000
1mNlm
mNlm

6mNlm

9mN"
10mNlm

a 1mNlm



0 20 40 60 80 100
Number of E-caprolactone units


Figure 4-12. Plots of MMA versus number of e-caprolactone repeat units for different surface
pressures from the isotherms of Star#3, Star#4, Star#5, and Star#6.

25


20 I PEO core extrapolated

E 9+ PEO2000
15




10



SArea per ethy-lene oxide~ unit (ii) 6


Figure 4-13. Isotherms of the PEO core extrapolated and PEO2000 normalized with respect to
the number of ethylene oxide units.











Z ~- Star#6G
E --Star#5
0.21
E L IStar#4
Star#3
S0.17
-- Star#2
Star#1







2 4 6 8 10 12 14 16
x; (mN/m)

Figure 4-14. Compressibility plots of the star-shaped PEO-b-PCL block copolymers versus
surface pressure.

4.2.3.2 Intermediate MMA region

This region is characterized by a pseudoplateau in the isotherms and by a maximum in the

compressibility plot (Figure 4-14). This phase transition occurs between approximately 12 and

15 mN/m, a similar pressure range as for the collapse pressure of PCL homopolymers. The

pseudoplateau length correlates with the PCL chain length in the stars, and this phase transition

is attributed to the PCL segments aggregating and crystallizing above the interface and the PEO

core, which is consistent with the work reported by Lee et al. on PCL-based block copolymers

with a dendritic hydrophilic head.120

Crystallization of the PCL segments was also characterized by carrying out isobaric

experiments for Star#6 with target pressures below and within the pseudoplateau pressure range

(9, 11, and 13 mN/m). The results of MMA decrease versus time are presented in Figure 4-15,

and the y-axis has been normalized to facilitate comparison. No or very little MMA decrease

takes place over time for pressures below the pseudoplateau (9 and 11 mN/m), which is

indicative of thermodynamically stable monolayers. As the target pressure is increased (13










mN/m), PCL quickly collapses and crystallizes as indicated by the sharp initial area decrease.

The MMA levels off around 1000 A+2, a value that correlates well with the MMA value obtained

at the end of the plateau in the isotherm.






S0.8-
.) *9mNim
-e11mNim
eJ0 o 13mN/m
S.6 -i o




0.4
0 10000 20000 30000
Time (s)


Figure 4-15. Isobaric relaxation plots of Star#6 at 9, 11, and 13 mN/m.

PCL crystallization in the pseudoplateau region was finally investigated by hysteresis

experiments. The compression-expansion curves for Star#6 with a target pressure of 15 mN/m

are shown in Figure 4-16. As the barriers expand, an expansion pseudoplateau appears that

corresponds to the readsorption (melting) of the PCL chains previously crystallized.

Interestingly, the second and third compression curves overlap each other but do not overlap the

initial compression, with a slight shift toward the low MMA region and a decrease in the

compression pseudoplateau pressure. Similarly as it was observed for PCL homopolymers, this

confirms that crystallization takes place for Star#6 in the pseudoplateau region during

compression. Star#5, Star#4, and Star#3 have a similar behavior with the expansion

pseudoplateau vanishing as the PCL amount is decreased. Because of even lower PCL content in

Star#2 and Star#1, no expansion pseudoplateau was observed, and the subsequent compression-










expansion isotherms shifted toward smaller mean molecular areas because of irreversible

polymer dissolution in the water subphase (Figure 4-17), similarly as for low surface pressures.

25


20
a First impression
ti15 -1 r First expansion
I ca Second and third conspressionsa
E I Second and third expansionss
S10-





0 2000 4000 6000 8000 10000 12000
MMA (A Z)

Figure 4-16. Compression-expansion hysteresis plot of Star#6 (target pressure = 15 mN/m).

25

20
h First compression
15 B First expansion
a Second compression
E I Second expansion
S10





0 500 1000 1500 2000 2500 3000
MMA (j2)


Figure 4-17. Compression-expansion hysteresis plot of Star#1 (target pressure = 15 mN/m).

4.2.3.3 Low MMA region

In the low MMA region, the surface pressure sharply increases up to values as high as 35

mN/m. Such high surface pressures can be reached because of the increased amphiphilicity of

the block copolymers compared to the homopolymers, even if the collapse pressure of the

individual PEO and PCL blocks is surpassed. The fact that the isotherms of Star#6, Star#5,









Star#4, and Star#3 overlap in this region suggests that all the PCL chains have collapsed and

crystallized above the interface, and that the sharp pressure increase arises mainly from

interactions between the hydrated PEO cores. Therefore, PCL crystallization probably takes

place for these four stars with the PEO core still hydrated in the water subphase, with the PCL

chains stretching and crystallizing away from the interface. The isotherms of Star#2 and Star#1

shift toward smaller mean molecular areas because of the water solubility behavior mentioned

before. A cartoon of the polymer chains' conformations as the Langmuir monolayers are

compressed is proposed in Figure 4-18. It should be mentioned that the experiments discussed

here do not provide enough information to fully understand the aggregation of the star-shaped

PEO-b-PCL block copolymers. For instance, eventual phase separation between the different

blocks leading to the formation of various surface micelles could not be directly determined from

surface pressure measurements.

O e-caprolactone repeat unit

*ethylene oxide repeat unit


High MMLA reon~l~ ~N


air


Figure 4-18. Proposed conformations modeling the adsorption of the star-shaped block
copolymers at the A/W interface versus surface pressure.


Intermediate MMLA region
(12mN/mc



Low MMLA region
(x>15mN/m)









4.2.3.4 AFM imaging

Typical AFM images of the star-shaped block copolymers LB films are presented in Figure

4-19 at pressures below (ri= 10 mN/m) and above (ri= 30 mN/m) the pseudoplateau. Similarly

as for PCL homopolymers, crystalline domains are observed for all the stars independent of the

surface pressure except for Star#1, which was unable to crystallize and only aggregated into

dewetted domains (~ 1-2 nm thick). Crystallization in PEO-b-PCL systems has been extensively

investigated in the previous literature, but the number of variables influencing crystallization

rates and morphologies is too large to allow any kind of generalization. For instance, Deng et al.

reported that, in PEO-b-PCL four-arm stars, PCL crystallinity for a constant PCL chain length

decreased as the PEO chain length was increased.114 Gan et al. observed that hydrophilic and

highly flexible PEO segments enhance the hydrophilicity and reduce the degree of crystallinity

of the polyester. The PEO block was also shown to provide nucleation sites for the crystallization

of the PCL block.137 CryStallization of PEO-b-PCL block copolymers in thin films resulted in

various types of spherulitic growths with crystallization of both PEO and PCL blocks.138-140

Nevertheless, it was widely demonstrated that PEO and PCL crystallize in well-defined

separated areas after their phase separation.141 Therefore, as PEO crystallization is obviously

difficult in LB films, probably as a result of residual hydration, we can reasonably assume that

the crystals obtained on mica substrates are the result of PCL crystallization only. Section

analysis indicates a constant crystal thickness around 7.5 nm, which is consistent with the

lamellae thickness obtained for PCL homopolymers.


















20i nm

10 nm

0 nm










Figure 4-19. Topographic AFM images of the star-shaped PEO-b-PCL copolymers LB films
transferred below and above the pseudoplateau: Star#1 at 10 (a) and 30 mN/m (b);
Star#2 at 10 (c) and 30 mN/m (d); Star#3 at 10 (e) and 30 mN/m (f); Star#4 at 10 (g)
and 30 mN/m (h); Star#5 at 10 (i) and 30 mN/m (j); Star#6 at 10 (k) and 30 mN/m (1).


From the previously reported literature, the PCL crystal unit cell has a length of 1.7297 nm

that corresponds to two e-caprolactone repeat units.142 PCL crystal thickness after transfer is

around 7.5 nm for all the star-shaped block copolymers, and if it is assumed that the PCL chains

orient perpendicularly to the mica substrate, this thickness indicates that the chains fold

approximately every eight e-caprolactone repeat units. This would also support why the stars

with a number of e-caprolactone repeat units per PCL chain greater or close to eight all

crystallized (Star#6, Star#5, Star#4, Star#3, and Star#2), whereas Star#1, with only three repeat

units per PCL chain, did not.

Similarly as for PCL homopolymers, the star-shaped samples exhibited PCL crystals at

low and high pressures, before and after crystallization of the PCL block at the A/W interface.









Additional crystallization of the PCL segments therefore also took place during and after transfer

for the star-shaped block copolymers, which likely leads to a mica surface only partially covered

with adsorbed or crystallized polymer chains. At high surface pressures, dendritic and needlelike

crystals could be seen. These crystal structures are significantly different from those observed for

PCL homopolymers, which indicates that even though the PEO core did not crystallize, it

strongly influenced the crystallization of the PCL blocks in terms of crystal morphology. Many

variables have to be taken into consideration, such as molecular weight, PEO amount, film

thickness, water evaporation, residual water content, transfer pressure, and substrate affinity for

the polymer chains to fully investigate crystallization of PCL homopolymers and PCL-based

block copolymers in LB films. While this study gives some hint of the surface properties of these

interesting star-shaped block copolymers, complete understanding of the system will therefore

require further investigation.

4.2.4 PEO-b-PCL Linear Diblock Copolymers

The PEO segment of the linear diblock copolymers (PEO2670, Mn = 2,670 g/mol) has a

molecular weight in the same range as the one of the PEO core of the star-shaped PEO-b-PCL

samples. Nevertheless, because of its linear architecture, this PEO segment has intrinsic surface

activity as shown in Figure 4-3, which should lead to the appearance of PEO phase transitions

not observable for the star-shaped samples in the low surface pressure region. The isotherms of

the four linear PEO-b-PCL diblock copolymers are presented in Figure 4-20. Compared to the

homopolymers PEO2670 and PCL2000 (PCL homopolymer with a molecular weight in the same

range as the PCL blocks of the linear diblock copolymers), higher surface pressures as high as 25

mN/m can be reached, similarly as for the star-shaped samples. As better shown in the

compressibility plot (Figure 4-21), three phase transitions that correspond to conformational

rearrangements of the polymer chains are clearly observed around 6.5, 10.5, and 13.5 mN/m. The








local maxima in monolayer compressibility for the two low pressure transitions increase as the

PCL chain length decreases, suggesting PEO-related phase transitions as previously observed for

comb-like polymers consisting of a poly(vinyl amine) backbone with 2kDa PEO side chains.143

The maximum in monolayer compressibility for the high pressure transition increases as the PCL

chain length increases, suggesting a PCL-related phase transition. Comparison with the

isotherms of PEO2670 and PCL2000 indicates that the transitions around 6.5 and 13.5 mN/m

arise from dissolution of the PEO block in the water subphase and crystallization of the PCL

block above the water surface, respectively. The transition at 10.5 mN/m was not observed for

PEO2670, but has been previously described as a brush formation of the PEO chains stretching

away from the interface when anchored by hydrophobic blocks for other PEO-based amphiphilic

block copolymers.144,145 In the following, we report our investigations on the behavior of the

linear PEO-b-PCL diblock copolymers in the low (r < 12 mN/m) and high (r > 12 mN/m)

surface pressure regions.

30

25 -1 \ PEOo-b-PCL,,
I~ PEOo-b-PCL27
E 20 -- PEOo-b-PCL19
7 ~- PEOo-b-PCL,
E 15-







0 2000 4000 6000
Mean Molecular Area (A2)

Figure 4-20. Isotherms of the PEO-b-PCL linear diblock copolymers.












0.2 PEOso-b-PCL, ~~1~
E~ PEOo-b-PCL,
~20.16-


0.12


0.08

2 4 6 8 10 12 14 16
x; (mN /m)

Figure 4-21. Compressibility plots of the PEO-b-PCL linear diblock copolymers versus surface
pressure.

4.2.4.1 Low surface pressure region (ir< 12 mN/m)

For surface pressures lower than the PEO aqueous dissolution around 6.5 mN/m, both the

PEO and the PCL blocks are adsorbed at the A/W interface in a pancake conformation. To

investigate the 2-dimensional miscibility of the two blocks in more details, we prepared

Langmuir monolayers with binary mixturesl46-14 Of PEO2670 and PCL2000, and the resulting

isotherms are presented in Figure 4-22. Contrary to the isotherms of the linear diblock

copolymers, only 2 phase transitions corresponding to PEO2670 aqueous dissolution (around 6.5

mN/m) and PCL2000 crystallization (around 13 mN/m) are observed. The absence of a phase

transition at 10.5 mN/m comes from the fact that PEO2670, which is not chemically anchored by

a hydrophobic PCL segment, is already irreversibly dissolved at this surface pressure in the

water subphase. This aqueous dissolution of PEO2670 (loss of material in the monolayer by

solubilization in the subphase) can be observed more clearly in the hysteresis experiment in

Figure 4-23 (49 mol % of PEO2670), with a target surface pressure of 9 mN/m, where the


0.24









successive compression-expansion curves shift toward the low MMA region only below 6.5

mN/m. Above 6.5 mN/m, the curves overlap because the amount of PCL2000 adsorbed at the

A/W interface stays constant, independent of the number of compression-expansion hysteresis

cycles.




*E 0 mol% PCL2000
E 10 -1 \\ 28 mol% PCL2000
Z 51 mol% PCL2000
0 I 70 mol% PCL2000
"~~ 6 10 86 mol% PCL2000
xc (mNlm)
-100 mol% PCL2000


0 1000 2000 3000 4000
Mean Molecular Area (A2)

Figure 4-22. Isotherms of PEO2670 and PCL2000 binary mixtures. (Inset) Corresponding
compressibility plots versus surface pressure.


*First compression
8 First expansion
E o Second compression
S 6 *Second expansion






0 1000 2000 3000 4000
Mean Molecular Area (A2)

Figure 4-23. Compression-expansion hysteresis plot of the binary mixture with 49 mol % in
PEO2670 (target pressure = 9 mN/m).

It is also interesting to notice that the collapse surface pressure of PEO2670 slightly

increases (up to 6.7 mN/m for 86 mol % of PCL2000) when increasing the amount of PCL2000









in the mixed monolayers, as shown by the shift of the compressibility maximum toward higher

surface pressures (inset of Figure 4-22). This is a first indication that PEO2670 and PCL2000

are miscible when both blocks are adsorbed at the A/W interface."s Figure 4-24 shows plots of

MMA versus the mole fraction of PCL2000 for three surface pressures below 6.5 mN/m (2, 3,

and 4 mN/m). The data exhibit negative deviations from ideal mixing (dashed lines), which

confirms that in the surface pressure range where they are adsorbed at the A/W interface (7<< 6.5

mN/m), PCL2000 and PEO2670 do not phase-separate and thermodynamically interpenetrate

each other.151,152 From these results, we can reasonably extrapolate that the PEO and PCL

segments of the linear diblock copolymers are miscible as well below 6.5 mN/m, and therefore

that their A/W interfacial adsorption probably does not lead to the formation of surface micelles

previously observed for other amphiphilic block copolymers.97,153,154 These results are in good

agreement with a previous study that demonstrated the miscibility of PEO and PCL

homopolymers in the amorphous phase in blend films prepared by solution casting.'


S2000
<(~ As = 2 m Nlm
= 3 mNlm
Q) I a = 4 mNlm







S600
2 0 0.2 0.4 0.6 0.8 1
PCL2000 mole fraction

Figure 4-24. MMA plots versus mole fraction of PCL2000. Dashed lines: theoretical ideal
mixing.









The reversibility of the two PEO phase transitions of the linear diblock copolymers was

investigated by carrying out compression-expansion hysteresis experimentS110,15 On the block

copolymer sample with the smaller PCL segment (PEO60-b-PCLll) for ai target pressure of 18

mN/m. The resulting x/1I1VA curves and the corresponding compressibility plots are shown in

Figures 4-25 and 4-26, respectively. After the first compression, the curves in Figure 4-25 shift

to the low IV1VA region, which is indicative of some irreversibility in the PEO phase transitions.

As shown in the compressibility plots, the local maximum at 6.5 mN/m disappears after the first

compression whereas the maximum at 10.5 mN/m is still present, independent of the number of

compression-expansion cycles. At 6.5 mN/m, we believe the PEO chains dissolve irreversibly in

the aqueous subphase and adopt a mushroom conformation. Nevertheless, because of the

anchoring effect of the PCL segments, the PEO chains stay in the vicinity of the interface. Upon

further monolayer compression, the PEO chains are compressed against each other and stretch

perpendicularly to the interface to form a compact brush at 10.5 mN/m.22,23,144,157-160 During

monolayer expansion, the PEO brush reversibly relaxes, but the PEO chains do not readsorb and

stay hydrated underneath the interface, which explains the complete absence of phase transition

at 6.5 mN/m after the first compression. The maximum in compressibility corresponding to the

transition at 10.5 mN/m is nevertheless slightly decreased after the first compression, which

suggests that the PEO chains do not completely relax during the subsequent expansions to their

original mushroom conformation of the first compression. It should be noticed that, contrary to

our linear PEO-b-PCL diblock copolymers, only one apparent PEO phase transition around 10

mN/m is usually observed in the isotherms of PEO-based block copolymers with high molecular

weight PEO blocks (Mn > 10,000 g/mol),22 prObably because PEO aqueous dissolution and brush

formation take place simultaneously.








20


E


0 1000 2000 3000
Mean Molecular Area (A2)


Figure 4-25. Compression-expansion hysteresis plot of PEO60-b-PCLll (target
mN/m).


pressure = 18


0.25


0.2


0.15




0.05


I
E
E
c


8 12
n; (mN Im)


16


Figure 4-26. Compressibility plots of Figure 4-25 (PEO60-b-PCLll, target pressure = 18 mN/m).
Top curve: first compression. Bottom curve: first expansion, second compression, and
second expansion.


4000










4.2.4.2 High surface pressure region (fr> 12mN/m)

In this surface pressure region, similarly as for the PCL homopolymers and the star-shaped

block copolymers, the phase transition observed in Figures 4-20 and 4-21 at 13.5 mN/m arises

from collapse and crystallization of the PCL segments above the water surface. The

compression-expansion hysteresis experiment carried out on the linear block copolymer sample

with the longest PCL block (PEO60-b-PCL35) for a target pressure of 16 mN/m gives more

insight on the crystallization/melting behavior of the PCL segments. The n/~MMA curves and the

corresponding compressibility plots are shown in Figures 4-27 and 4-28, respectively. During

monolayer compression, the hydrophobic PCL segments collapse and crystallize on top of the

water surface as shown by the inflection points in the 2/MMA curves and the local maxima in

the compressibility plots at 12.5 and 13.5 mN/m. Similarly as for the PCL homopolymers and for

the star-shaped samples, the collapse/crystallization surface pressure in the first cycle is

approximately 1 mN/m higher than in the subsequent compressions (13.5 versus 12.5 mN/m),

and also, after the first compression, the subsequent curves are slightly shifted toward the low

mean molecular area region. After the first hysteresis cycle, the PCL crystals that did not melt

(i.e. did not readsorb at the A/W interface) act as nucleation sites to catalyze the crystallization of

other PCL segments during the subsequent cycles, therefore lowering the crystallization surface

pressure and shifting the compression isotherms toward lower mean molecular areas. During

monolayer expansion, melting of the PCL segments was characterized in the 2/MMA plots for

the star-shaped samples and the PCL homopolymers by an expansion pseudoplateau at a surface

pressure lower than for the crystallization. As shown in Figures 4-27 and 4-28, no pseudoplateau

or sharp local maximum in compressibility are observed during the first expansion, whereas for

the subsequent cycles the PCL segments clearly readsorb around 5 mN/m (sharp local maximum








in the compressibility plot). The presence of a broad melting transition during the first monolayer

expansion is a little bit surprising because this behavior was not previously observed for the star-

shaped samples and the PCL homopolymers, but it is probably related to a particular shape, size,

or polydispersity of the PCL crystals formed during the first monolayer compression. It should
be noticed that the crystallization and melting surface pressures reported here for linear diblock

copolymers (as well as for the star-shaped block copolymers and the PCL homopolymers) are
not thermodynamic values and were shown to be strongly barrier speed dependent. If one could

compress and expand the monolayers infinitely slowly, the crystallization and the melting
surface pressures would respectively decrease and increase, probably leveling off to a common
value.

20
*First compression
ai First expansion
15- o Sec~ond and third co~mpressions
E Second and third expansions

E 10







O 2000 4000 6000
Mean Molecular Area (A2)

Figure 4-27. Compression-expansion hysteresis plot of PEO60-b-PCL35 (target pressure = 16
mN/m).








0.45


0.35
~ d
zc b
--0.25


S0.15


0.05

1 3 5 7 9 11 13 15
x; (m Nlm)

Figure 4-28. Compressibility plots of Figure 4-27 (PEO60-b-PCL35, target pressure 16 mN/m).
a: PCL crystallization at 13.5 mN/m during the 1st compression. b: PCL
crystallization at 12.5 mN/m during the 2nd and 3rd COmpressions. c: broad PCL
melting transition during the 1st expansion. d: PCL melting transitions during the 2nd
and 3rd expansions.

Crystallization of the linear PEO-b-PCL diblock copolymers in the LB monolayers was

finally evidenced by AFM imaging after transfer onto mica substrates for surface pressures

above 13.5 mN/m, after crystallization of the PCL segments on the water surface took place. As

shown in Figure 4-29 for a surface pressure of 15 mN/m, all the samples show hair-

like/needlelike crystal structures, with a constant crystal thickness around 7.5 nm as determined

from cross-section analysis. This thickness is consistent with the value obtained for the PCL

homopolymers and the star-shaped block copolymer samples. The PEO chains are adsorbed onto

the mica substrate and the PCL segments stretch perpendicularly to the interface, folding

approximately every 8 e-caprolactone repeat units. These results confirm what we observed for

the star-shaped PEO-b-PCL samples, where the PEO block highly influenced crystallization of

the PCL segments in terms of crystal morphology. Nevertheless, it is crucial to emphasize here









once again that this brief crystal structure analysis is done for the LB films only and is not

rigorously valid for Langmuir monolayers, because film drying during LB film formation can

lead to further crystallization of the PCL segments. Evidence for crystallization of the PCL

segments in the star-shaped and the linear block copolymer samples directly at the A/W interface

came from the isotherms, the hysteresis, and the isobaric experiments, but no clear conclusions

can yet be drawn in terms of crystal structures in the Langmuir monolayers. BAM experiments

are currently underway to investigate more deeply the in-situ and real-time PCL crystal

growth/melting directly on the water surface for the star-shaped and the linear PEO-b-PCL block

copolymers.






50n 50n 5nm1



25nm 25nm 25nm

0 nm 20 nm 0 n





S- 20 nm 2u
50nm 50nm 7.5 nm



0 nm 0 nm

Figure 4-29. Topographic AFM images of the linear PEO-b-PCL diblock copolymers LB films
transferred after crystallization of the PCL segment at the A/W interface (7<= 15
mN/m). (a): PEO60-b-PCLll (b): PEO60-b-PCL19 (c): PEO60-b-PCL27 (d) and (e):
PEO60-b-PCL35 (f): CTOss-section analysis on PEO60-b-PCL35










A cartoon summarizing the polymer chains conformations as the Langmuir monolayers of

the linear PEO-b-PCL diblock copolymers are compressed is proposed in Figure 4-30. For

surface pressure values lower than 6.5 mN/m, both the PEO and the PCL segments are adsorbed

at the A/W interface in a pancake conformation (1). As the surface pressure is increased, the

PEO segments irreversibly dissolve in the aqueous subphase and adopt a mushroom

conformation around 6.5 mN/m (2), before forming a brush above 10.5 mN/m upon further

compression (3). Finally, around 13.5 mN/m, the PCL segments collapse and crystallize

perpendicularly to the interface (4).


Ethylene oxide repeat unit
O e-caprolactone repeat unit

(2) 6.5 mN/m < xr < 10.5 mN/m


(1) x < 6.5 mN/m


Air






(3) 10.5 mN/m < 7x7 < 13.5 mN/m


Water


Water


Figure 4-30. Proposed conformations modeling the adsorption of the linear PEO-b-PCL diblock
copolymers at the A/W interface versus surface pressure.


(4) 13.5 mN/m < r









4.3 Conclusions

In this chapter, the A/W interfacial behavior of various PEO-b-PCL block copolymers and

their LB film morphologies on hydrophilic mica substrates were investigated, and the results

were compared to PEO and PCL homopolymers. The isotherms of the star-shaped block

copolymers indicated the presence of a single phase transition characterized by a pseudoplateau

that corresponds to the collapse and crystallization of the PCL chains above the water surface.

Below the plateau, the PCL segments are adsorbed, anchoring the water-soluble star-shaped PEO

core in the vicinity of the interface. Compression-expansion hysteresis experiments showed that,

in this region, the spread monolayers are thermodynamically stable except the ones containing

the smallest PCL amounts, which irreversibly dissolved in the water subphase. In the

pseudoplateau region, PCL homopolymers crystallized directly at the A/W interface as well as

the PCL segments of the star-shaped block copolymers. Above the pseudoplateau, the isotherms

of the star-shaped block copolymers with the longest PCL chains overlapped, indicating that all

the PCL chains have collapsed and that the sharp pressure increase mainly arises from

interactions between the hydrated PEO cores. Compression-expansion hysteresis experiments

indicated that the readsorption/melting of the PCL segments takes place at a lower surface

pressure than for the crystallization. AFM imaging of the homopolymers and the star-shaped

block copolymers LB films was complicated by the fact that both PEO and PCL are highly

crystalline polymers that can undergo morphological changes during monolayer transfer. The

PEO homopolymers did not crystallize, probably because residual hydration or large hydrophilic

substrate/PEO monolayer interactions inhibited crystal formation. The PCL homopolymers and

the star-shaped block copolymers crystallized directly at the A/W interface only above the PCL

collapse pressure, but additional crystallization could take place during water evaporation on the

mica substrates. Various crystal morphologies were observed for the star-shaped block










copolymers such as spherulitic, dendritic, and needlelike structures, with the presence of the PEO

core strongly influencing the crystallization of the PCL blocks. The linear diblock copolymers

successfully self-assembled as well at the A/W interface to form stable Langmuir monolayers.

Preliminary investigation on PEO2670 and PCL2000 homopolymers blends showed that these

polymers are non-ideally miscible for low surface pressures when both blocks are adsorbed at the

A/W interface. Nevertheless, the individual collapse surface pressures (PEO2670 aqueous

dissolution around 6.5 mN/m and PCL2000 crystallization above the interface around 13 mN/m)

were not significantly influenced by the presence of the other homopolymer. For the linear PEO-

b-PCL diblock copolymers, an additional PEO phase transition at 10.5 mN/m was observed

corresponding to the formation of a PEO brush underneath the anchoring PCL segments. These

two PEO phase transitions were not observed for the star-shaped PEO-b-PCL block copolymers,

and our investigations consequently confirmed the significant influence of the polymer

architecture on its interfacial properties. AFM imaging of the linear PEO-b-PCL diblock

copolymers LB fi1ms for high surface pressures confirmed the formation of PCL crystals with

hairlike/needlelike architectures. These crystals were significantly different from those obtained

in LB films of PCL homopolymers, confirming the strong influence of the PEO block on the

crystallization of the PCL segments. This fundamental investigation gave interesting insight on

the interfacial self-assembly of PEO-b-PCL copolymers and showed that an accurate and easy

control of the conformations and the orientations of the different blocks at the A/W interface can

be easily achieved by simply varying the polymer architecture or the surface pressure.

4.4 Experimental Methods

4.4.1 Langmuir Films

Surface pressure measurements were accomplished by use of a Teflon Langmuir trough

system (W= 160 mm, L = 650 mm; KSV Ltd., Finland) equipped with two moving barriers and a









Wilhelmy plate. Between runs, the trough was cleaned with ethanol and rinsed several times with

Millipore filtered water (resistivity > 18.2 MGZ.cm). The samples were typically prepared by

dissolving approximately 1 mg of polymer in 1 mL of chloroform. Volumes ranging from 10 to

30 puL were spread dropwise on a Millipore filtered water subphase with a gastight Hamilton

syringe. The chloroform was allowed to evaporate for 30 min to ensure no residual solvent

remained. When not in use, the volumetric flasks containing the polymer solutions were wrapped

with Teflon tape followed by Parafilm and stored at 10 OC in order to prevent changes in

concentration due to chloroform evaporation. In all the experiments, subphase temperature and

barrier speed were kept constant at 25 OC and 5 mm/min, respectively, unless otherwise stated.

4.4.2 AFM Imaging

The LB films were formed by transferring the Langmuir films of the PEO-b-PCL block

copolymers (linear and star-shaped) and the homopolymers onto freshly cleaved mica at the

desired surface pressure which was attained at compression/expansion rates of +/-5 mm/min.

Once the films had equilibrated at a constant surface pressure for 15 min, the mica substrate was

then pulled out of the water subphase at a rate of 1 mm/min. All the transfer ratios were close to

unity unless otherwise stated, which is indicative of successful transfer. The transferred films

were air-dried in a desiccator for 24 h and subsequently scanned in tapping mode with a

Nanoscope III AFM (Digital Instruments, Inc., Santa Barbara, CA) by use of Nanosensors

silicon probes (dimensions: T = 3.8-4.5 pum, W = 26-27 pum, L = 128 pum). All the images were

processed with a second-order flattening routine.









CHAPTER 5
TWO-DIMENSIONAL POLYMERIC NANOMATERIALS THROUGH CROSS-LINKING
OF POLYBUTADIENE-b-POLY(ETHYLENE OXIDE) MONOLAYERS AT THE
AIR/WATER INTERFACE

5.1 Introduction

The idea of stabilizing amphiphilic self-assemblies by polymerization was introduced at

least thirty years ago for monolayers and about ten years later for bilayer vesicles.161,16 This

approach to bridging the nanoscale world of labile, interfacially driven self-assemblies with the

meso-scale has resulted in several examples of cross-linked 3D structures.163-16 For example,

Bates and co-workers were the first to succeed in retaining the cylindrical morphology formed by

gigantic wormlike rubber micelles of polybutadiene-b-poly(ethylene oxide) (PB-b-PEO) diblock

copolymers in water by chemical cross-linking of the PB cores through their pendant 1,2-double

bonds.163,167,168 However, relatively few groups have shown interest in stabilization by cross-

linking of two-dimensional (2D) polymeric self-assemblies formed at the air/water (A/W)

interface; most studies have involved interfacial polymerization of small molecules in Langmuir

monolayers.16-9

In the early 1970's, Veyssie and co-workerS180,190,191,193 were the first to demonstrate the

formation of 2D cross-linked materials by cross-linking monolayers of dimethacrylates and

several other difunctional reactive amphiphiles under UV irradiation for a constant surface

pressure at the A/W or the oil/water interface. This idea inspired other research groups and

several examples followed. Regen and co-workers introduced the concept of a 2D-network of

molecular pores, i.e. "perforated monolayers" derived from calix[n]arene-based amphiphiles.183-

Iss Cross-linking with malonic acid or via UV irradiation enabled them to synthesize porous and

cohesive "perforated monolayers" with pore diameters in the range 2-6 A+ potentially applicable

for gas permeation selectivity.186,187,189 Michl and co-workers synthesized grids through the









coupling of star-shaped monomers forced to adhere to a mercury surface.194,195 After

polymerization, well-defined covalent 2D square- or hexagonal-grid polymers could be

synthesized,194,195,199 and analogous supramolecular routes were also proposed.200-202 Palacin and

co-workers reported on cross-linking porphyrins through molecular recognition between

oppositely charged monomers at the A/W interface.196-19 Kloeppner and Duranl7 were the first

to demonstrate the possibility to remove from the water surface free-standing fibers of 2D cross-

linked 1,22-bis(2-aminophenyl)docosane polyanilines. Finally, alkylalkoxysilanes have been

widely used, 177-179,203,204 and our group has for instance investigated some of the fundamental

aspects of the A/W interfacial cross-linking of octadecyltrimethoxysilane (OTMS) and

octadecyltriethoxysilane (OTES) under acidic conditions.177-179,203 However, relatively few

groups have shown interest in stabilizing by cross-linking 2D "true" polymeric self-assemblies at

the A/W interface. To our knowledge, only one example based on a lipopolymer was previously

proposed by O'Brien and co-workers involving network formation by photopolymerization.205

Our interest is to cross-link monolayers of block copolymers to achieve porosity at the sub-

micrometer scale. In this chapter, the synthesis of a 2D polymeric nanomaterial consisting of a

continuously cross-linked PB network containing PEO domains of controllable size is illustrated.

This work was done in collaboration with Rachid Matmour, graduate student in the Duran group

at the University of Florida. Such thin films have potential applications in the preparation of

membranes which will show large differences in permeability to water, methanol, and other

polar compounds, depending on the PEO "pore" size.

We report in this chapter the 2D self-condensation, at the A/W interface and under acidic

conditions, of a triethoxysilane-functionalized PB-b-PEO three-arm star block copolymer (PB

core and PEO corona) and of a triethoxysilane-functionalized linear PB homopolymer in a









preliminary investigation. Using PB, which pendant double bonds have been hydrosilylated with

trialkoxysilanes, as the cross-linkable block is a novel approach that can be applicable to a

variety of other polydiene-based block copolymers in order to retain a specific morphology at the

nanoscopic scale. The surface properties of the cross-linked monolayers were characterized by

surface pressure measurements such as surface pressure (7r)-mean molecular area (MMA)

isotherms at different reaction times, and isobaric experiments for various subphase pH values.

The morphologies of the Langmuir monolayers were studied by atomic force microscopy (AFM)

imaging of the corresponding Langmuir-Blodgett (LB) films.

5.2 Results and Discussion

5.2.1 Hydrosilylated PB Homopolymer

5.2.1.1 Hydrosilylation reaction

To demonstrate the viability of the 2D cross-linking method, we chose to first focus on a

commercially available linear PB homopolymer (Mn = 11,050 g/mol, ~ 204 butadiene repeat

units). Many publications and patents can be found in the literature on the hydrosilylation of

polymers.206-21 In mOst cases, the hydrosilylated polydienes were used as precursors to

synthesize macromolecular complex architectures such as arborescent graft polybutadienes,218

multigraft copolymers of PB and polystyrene,219 Or side-loop polybutadienes.220 Triethoxysilane

was used here as the pendant double bond hydrosilylating agent in stoichiometric amount with

the total molar amount of repeat units in the PB homopolymer and in the presence of Karstedt

catalyst (platinum catalyst) as shown in Figure 5-1. The reaction was carried out under argon for

24 h at 80 oC in dry toluene (water free environment). After workup, the hydrosilylated PB was

analyzed by 1H NMR and FTIR spectroscopies (Figures 5-2, 5-3, and 5-4).




Full Text

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1 TWO-DIMENSIONAL SELF-ASSEMBLY OF AMPHIPHILIC BLOCK COPOLYMERS AT THE AIR/WATER INTERFACE AND NANOPA RTICLES FOR DRUG DETOXIFICATION APPLICATIONS By THOMAS J. JONCHERAY A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLOR IDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2006

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2 Copyright 2006 by Thomas J. Joncheray

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3 ACKNOWLEDGMENTS First and foremost, I would like to thank my parents, Dominique Joncheray and Catherine Stona, my sister, Alice Joncheray, as well as the rest of my famil y, past and presen t, for being an endless source of support in my education a nd life. In February 2001, I met Emilie Galand in Bordeaux who came to the University of Florida w ith me where we spent together almost five years of graduate school. I could not have ach ieved this seemingly insurmountable amount of work without her. We supported each other th rough these challenging years, and helped each other through the difficult times. I would like to acknowledge my research dire ctor, Prof. Randolph S. Duran, for his help and support over the years I spen t under his supervision. His expe rienced advice has been an integral part of my education and has given me a deeper understanding of what is needed to be successful as a research chemist. I would like also to thank the othe r members of my Ph.D. committee: Prof. Kenneth B. Wagener, Dr. Ronald K. Castellano, Dr. Thomas J. Lyons, and Dr. Wolfgang M. Sigmund. I am also very grateful to the many collaborat ors I have had the chance to interact with over the years I spent in graduate school. I have had the pleasure of working with Prof. Audebert from ENS Cachan on the nanocapsule project. He provided very intere sting discussions and ideas, and always made himself available when I needed his help. I also really appreciated the collaboration on PEOb -PCL block copolymers I had with Pr of. Schubert and particularly with Dr. Mike Meier from the Eindhoven University of Technology. It was a pleasure to have Mike and Jutta staying for a few days at the University of Florida, and Emilie and I also enjoyed very much the time spent in Eindhoven. I express my appreciation to Pr of. Gnanou from the Laboratoire de Chimie des Polymres Organiques in Bordeaux, France, for his input in the PSb -

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4 P t BA, PSb -PAA, and PBb -PEO projects, and for helping me in joining the graduate program of the University of Florida. At the University of Florida, special thanks go to the polymer floor and the Chemistry Department staff, most notably Lorraine William s, Sara Klossner, and Lori Clark for their patience in answering my various questions. I want to show my gratitude to the three professors of the Butler Polymer Laboratory, Prof. Duran, Pr of. Wagener, and Prof. Reynolds, for putting a lot of effort in providing the polymer floor me mbers with a superior work environment to conduct research in polymer chemistry. I want to thank all my co-workers from the Duran group and from the George and Josephine Butler polymer floor. Special thanks need to go to Rachid Matmour, who made the time spent in the lab rea lly enjoyable. It was a pleasure working with him, often in a hilarious atmosphere, on severa l challenging research projects. Other group members to whom I owe extra thanks for their help along the way are Dr. Aleksa Jovanovic, Dr. Jennifer Logan, Jorge Chvez, Sophie Bernard, Brian Dorvel, Rita El-Khouri, Kristina Denoncourt, and Claire Mathieu. Finally, I would like to thank all the friends I have had the chan ce to meet and interact with inside or outside the Chemistry Department, esp ecially Benot Lauly, Christophe Grenier, Pierre Beaujuge, and Changhwan Ko who made my days in Gainesville very enjoyable.

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5 TABLE OF CONTENTS page ACKNOWLEDGMENTS...............................................................................................................3 LIST OF TABLES................................................................................................................. ..........8 LIST OF FIGURES................................................................................................................ .........9 ABSTRACT....................................................................................................................... ............15 CHAPTER 1 INTRODUCTION................................................................................................................. .17 1.1 Block Copolymers in the Bulk and in Solution................................................................17 1.2 Block Copolymers at the A/W Interface..........................................................................20 1.3 Current Status of Drug Detoxification Therapy...............................................................23 1.4 Nanoparticle Technology..................................................................................................24 1.5 Microemulsions and Sol-Gel Chemistry..........................................................................25 1.6 Molecular Imprinting and Mi niemulsion Polymerization................................................28 2 EXPERIMENTAL TECHNIQUES........................................................................................32 2.1 Langmuir Monolayers and Surface Pressure Related Experiments.................................32 2.2 Langmuir-Blodgett Films and Atomic Force Microscopy...............................................36 2.3 Transmission Electron Microscopy a nd Quasi-Elastic Light Scattering..........................39 2.4 Cyclic Voltammetry......................................................................................................... .41 3 POLYSTYRENEb -POLY( TERT -BUTYLACRYLATE) AND POLYSTYRENEb POLY(ACRYLIC ACID) DENDRIM ER-LIKE COPOLYMERS: TWODIMENSIONAL SELF-ASSEMBLY AT THE AIR-WATER INTERFACE......................44 3.1 Introduction............................................................................................................... ........44 3.2 Results and Discussion..................................................................................................... 46 3.2.1 PSb -P t BA Dendrimer-Like Copolymer................................................................46 3.2.2 PSb -PAA Dendrimer-Like Copolymer.................................................................52 3.3 Conclusions................................................................................................................ .......58 3.4 Experimental Methods......................................................................................................5 9 3.4.1 Materials................................................................................................................ .59 3.4.2 Langmuir Films......................................................................................................59 3.4.3 AFM Imaging.........................................................................................................60 4 LANGMUIR AND LANGMUIR-BLODG ETT FILMS OF POLY(ETHYLENE OXIDE)b -POLY(-CAPROLACTONE) STAR-SHAPED AND LINEAR BLOCK COPOLYMERS..................................................................................................................... 61

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6 4.1 Introduction............................................................................................................... ........61 4.2 Results and Discussion..................................................................................................... 64 4.2.1 PEO Homopolymers...............................................................................................64 4.2.2 PCL Homopolymers...............................................................................................67 4.2.3 Star-Shaped PEOb -PCL Block Copolymers.........................................................73 4.2.3.1 High MMA region........................................................................................73 4.2.3.2 Intermediate MMA region...........................................................................77 4.2.3.3 Low MMA region........................................................................................79 4.2.3.4 AFM imaging...............................................................................................81 4.2.4 PEOb -PCL Linear Diblock Copolymers...............................................................83 4.2.4.1 Low surface pressure region........................................................................85 4.2.4.2 High surface pressure region........................................................................90 4.3 Conclusions................................................................................................................ .......95 4.4 Experimental Methods......................................................................................................9 6 4.4.1 Langmuir Films......................................................................................................96 4.4.2 AFM Imaging.........................................................................................................97 5 TWO-DIMENSIONAL POLYMERIC NANOMATERIALS THROUGH CROSSLINKING OF POLYBUTADIENEb -POLY(ETHYLENE OXIDE) MONOLAYERS AT THE AIR/WATER INTERFACE....................................................................................98 5.1 Introduction............................................................................................................... ........98 5.2 Results and Discussion...................................................................................................10 0 5.2.1 Hydrosilylated PB Homopolymer........................................................................100 5.2.1.1 Hydrosilylation reaction.............................................................................100 5.2.1.2 Cross-linking reaction at the A/W interface...............................................103 5.2.1.3 AFM imaging.............................................................................................107 5.2.2 Hydrosilylated PBb -PEO Three-Arm Stars........................................................109 5.2.2.1 Hydrosilylation reaction.............................................................................112 5.2.2.2 Cross-linking reaction at the A/W interface...............................................115 5.2.2.3 AFM imaging.............................................................................................119 5.3 Conclusions................................................................................................................ .....124 5.4 Experimental Methods....................................................................................................125 5.4.1 Materials and Instrumentation..............................................................................125 5.4.2 Langmuir Films....................................................................................................126 5.4.3 Hydrosilylation of the PB Homopolymer.............................................................126 5.4.4 Hydrosilylation of the (PB200b -PEO326)3 Three-Arm Star Block Copolymer....127 5.4.5 A/W Interfacial Cross-Linking.............................................................................128 6 ELECTROCHEMICAL AND SPECTROSC OPIC CHARACTERIZATION OF ORGANIC COMPOUND UPTAKE IN SI LICA CORE-SHELL NANOCAPSULES......129 6.1 Introduction............................................................................................................... ......129 6.2 Results and Discussion...................................................................................................13 1 6.2.1 Nanocapsule Characterization..............................................................................133 6.2.2 Uptake Study........................................................................................................134 6.2.2.1 Optical measurements results.....................................................................136

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7 6.2.2.2 Electrochemical experiments.....................................................................138 6.3 Conclusions................................................................................................................ .....146 6.4 Experimental Methods....................................................................................................147 6.4.1 Nanocapsule Synthesis........................................................................................147 6.4.2 Transmission Electron Microscopy......................................................................147 6.4.3 Particle Size Analysis...........................................................................................148 6.4.4 Spectroscopy Measurements................................................................................148 6.4.5 Electrochemistry Experiments..............................................................................149 7 TOWARD SPECIFIC DRUG DETOXI FICATION AGENTS: MOLECULARLY IMPRINTED NANOPARTICLES.......................................................................................151 7.1 Introduction............................................................................................................... ......151 7.2 Results and Discussion...................................................................................................15 2 7.3 Conclusions................................................................................................................ .....160 7.4 Experimental Section......................................................................................................1 61 7.4.1 Materials...............................................................................................................1 61 7.4.2 Nanoparticle Synthesis.........................................................................................162 7.4.3 FTIR Spectroscopy...............................................................................................162 7.4.4 Particle Size Analysis...........................................................................................162 7.4.5 AFM Imaging.......................................................................................................163 7.4.6 Uptake Experiments.............................................................................................163 8 CONCLUSIONS AND PERSPECTIVES...........................................................................165 LIST OF REFERENCES............................................................................................................. 168 BIOGRAPHICAL SKETCH.......................................................................................................184

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8 LIST OF TABLES Table page 4-1 Characteristic values of the star-shaped polymers.............................................................63 4-2 Characteristic values of the linear PE O macroinitiator and of the linear diblock copolymers..................................................................................................................... ....64 4-3 Collapse pressure values of the PCL homopolymers........................................................69 5-1 Number average molecular weights and pol ydispersity indexes of the three-arm star block copolymers.............................................................................................................11 0 7-1 Loading compositions of the miniemulsions...................................................................154

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9 LIST OF FIGURES Figure page 1-1 Mean-field predication of the morphologies for confor mationally symmetric diblock melts.......................................................................................................................... .........18 1-2 Solution state for amphiphilic diblock copol ymers in water for concentrations below and above the CMC...........................................................................................................19 1-3 Spherical, rodlike, and vesicular morphologies for PSb -PAA crew-cut micelles............20 1-4 A schematic illustration showing the components of an amphiphile and the orientation of this amphiphile adopted at an interface.......................................................21 1-5 Transmission electron micrographs of LB films of poly(styreneb -vinylpyridinium decyl iodide) AB diblock copolymers...............................................................................23 1-6 Structure of normal and inverse spherical micelles formed in microemulsion systems....26 1-7 Sol-Gel hydrolysis and condensation reactions.................................................................27 1-8 Sol-Gel technologies and their products............................................................................28 1-9 Outline of the molecu lar imprinting strategy.....................................................................29 1-10 Examples of commercially available functional monomers and cross-linkers..................29 1-11 Principal of miniem ulsion polymerization.........................................................................31 2-1 The Langmuir Teflon trough.............................................................................................32 2-2 A Wilhelmy plate partially immersed in a water subphase...............................................33 2-3 Schematic isotherm for small amphiphilic molecules.......................................................35 2-4 LB film transfer onto a hydrophilic mica substrate...........................................................37 2-5 The AFM tapping mode electronic setup...........................................................................38 2-6 Specimen interactions in electron microscopy..................................................................39 2-7 Basic shape of the current response for a cyclic voltammetry experiment........................42 3-1 Schematic sketch of the PSb -PtBA (Dend1) and the PSb -PAA (Dend2) samples.........45 3-2 Isotherm of Dend1. (Inset) Static elastic modulus plot versus surface pressure...............47

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10 3-3 Topographic AFM images of Dend1 LB fi lms transferred at 5, 10, 15, 20, 24 (middle of plateau, MMA = 20,000 2), and 40 mN/m..................................................................49 3-4 Compression-expansion hysteresis plot of Dend1 (target MMA = 20,000 2).................50 3-5 Surface pressure/time isoc horic relaxation plot of Dend1 after compression up to 40 mN/m........................................................................................................................... ......51 3-6 Compression-expansion hysteresis plot of Dend1 (target pressure = 40 mN/m)..............52 3-7 Isotherm of PAA250K (pH = 2.5)........................................................................................53 3-8 Topographic AFM images of PAA250K LB films transferred at 1.5, 3, and 3.5 mN/m.....54 3-9 Isotherm of Dend2 (pH = 2.5). (Inset) Comp ressibility plot versus surface pressure.......55 3-10 Topographic AFM images of Dend2 LB fi lms transferred at 2, 4, 4.5, 5, 5.5, 6, and 8 mN/m........................................................................................................................... ......57 3-11 Compression-expansion hysteresis plot of Dend2 (target pressure = 5 mN/m, pH = 2.5)........................................................................................................................... ..........57 4-1 The star-shaped PEOb -PCL block copolymers................................................................63 4-2 The linear PEOb -PCL block copolymers.........................................................................64 4-3 Isotherms of the PEO homopolymers. (In set) Same isotherms normalized with respect to the number of ethylene oxide units...................................................................66 4-4 Compression-expansion hystere sis plot of the PEO core (target pressure = 2 mN/m)......66 4-5 Isotherms of the PCL homopolymers. (In set) Same isotherms normalized with respect to the number of -caprolactone units...................................................................68 4-6 Isotherms of the PCL homopolymers (compression speed = 100 mm/min).....................70 4-7 Compression-expansion hys teresis plot of PCL1250........................................................71 4-8 Topographic AFM images of PCL homopol ymers LB films transferred below and above monolayer collapse..................................................................................................72 4-9 Isotherms of the star-shaped PEOb -PCL copolymers......................................................73 4-10 Compression-expansion hysteresis plot of Star#6 (target pressure = 9 mN/m)................74 4-11 Compression-expansion hysteresis plot of Star#1 (target pressure = 9 mN/m)................74 4-12 Plots of MMA versus number of -caprolactone repeat units for different surface pressures from the isotherms of Star#3, Star#4, St ar#5, and Star#6..................................76

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11 4-13 Isotherms of the PEO core extrapolated and PEO2000 normalized with respect to the number of ethylene oxide units..........................................................................................76 4-14 Compressibility plots of the star-shaped PEOb -PCL block copolymers versus surface pressure............................................................................................................... ...77 4-15 Isobaric relaxation plots of Star#6 at 9, 11, and 13 mN/m................................................78 4-16 Compression-expansion hysteresis plot of Star#6 (target pressure = 15 mN/m)..............79 4-17 Compression-expansion hysteresis plot of Star#1 (target pressure = 15 mN/m)..............79 4-18 Proposed conformations modeling the adsorption of the star-shaped block copolymers at the A/W interface versus surface pressure.................................................80 4-19 Topographic AFM images of the star-shaped PEOb -PCL copolymers LB films transferred below and above the pseudoplateau................................................................82 4-20 Isotherms of the PEOb -PCL linear diblock copolymers..................................................84 4-21 Compressibility plots of the PEOb -PCL linear diblock copolymers versus surface pressure....................................................................................................................... .......85 4-22 Isotherms of PEO2670 and PCL2000 binary mixtures. (Inset) Corresponding compressibility plots versus surface pressure....................................................................86 4-23 Compression-expansion hysteresis plot of the binary mixture with 49 mol % in PEO2670 (target pressure = 9 mN/m)...............................................................................86 4-24 MMA plots versus mole fraction of PCL 2000. Dashed lines: theoretical ideal mixing....87 4-25 Compression-expansion hysteresis plot of PEO60b -PCL11 (target pressure = 18 mN/m).......................................................................................................................... ......89 4-26 Compressibility plots of Figure 4-25 (PEO60b -PCL11, target pressure = 18 mN/m)........89 4-27 Compression-expansion hysteresis plot of PEO60b -PCL35 (target pressure = 16 mN/m).......................................................................................................................... ......91 4-28 Compressibility plots of Figure 4-27 (PEO60b -PCL35, target pressure = 16 mN/m)........92 4-29 Topographic AFM images of the linear PEOb -PCL diblock copolymers LB films transferred after crystallization of the PCL segment at the A/W interface ( = 15 mN/m).......................................................................................................................... ......93 4-30 Proposed conformations modeling the adsorption of the linear PEOb -PCL diblock copolymers at the A/W interface versus surface pressure.................................................94 5-1 Hydrosilylation of the pendant double bonds of the PB homopolymer...........................101

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12 5-2 1H NMR spectrum of the PB homopolymer....................................................................101 5-3 1H NMR spectrum of the hydrosilylated PB homopolymer............................................102 5-4 FTIR spectra of the PB homopolym er before and after hydrosilylation.........................102 5-5 Cross-linking reaction involving hydrolysi s and condensation of the triethoxysilane groups......................................................................................................................... ......104 5-6 Surface pressure-Mean Mol ecular Area isotherms of the hydrosilylated PB carried out after different reaction times (subphase pH = 3.0)....................................................104 5-7 Static elastic modulus-surface pressu re curves of the hydrosilylated PB homopolymer at different reac tion times (subphase pH = 3.0).......................................105 5-8 MMA-time isobars of the hydrosilylated PB for various subphase pH values ( = 10 mN/m).......................................................................................................................... ....106 5-9 Removal of the cross-linked hydr osilylated PB from the water surface.........................107 5-10 AFM topographic images of the LB f ilms transferred onto mica substrates at = 10 mN/m........................................................................................................................... ....109 5-11 Surface Pressure-MMA isotherms for the (PB200b -PEOn)3 three-arm star block copolymers..................................................................................................................... ..111 5-12 Isotherm of (PB76b -PEO444)4 depicting how Apancake, Ao, and Apseudoplateau are determined..................................................................................................................... ...111 5-13 Linear dependence of Apseudoplateau on the total number of ethylene oxide units............112 5-14 Hydrosilylation of the pendant double bonds of the (PBb -PEO)3 three-arm star block copolymers.............................................................................................................11 3 5-15 1H NMR spectra of the (PB200b -PEO326)3 star block copolymer and the corresponding hydrosily lated (PB(Si(OEt)3)b -PEO)3 star block copolymer.................114 5-16 FTIR spectra of the (PB200b -PEO326)3 star block copolymer and the corresponding hydrosilylated (PB(Si(OEt)3)b -PEO)3 star block copolymer.........................................114 5-17 Surface Pressure-MMA isotherms of the (PB200b -PEO326)3 star block copolymer and of the corresponding hydros ilylated (PB(Si(OEt)3)b -PEO)3 star block copolymer before and after cross-linking..........................................................................................116 5-18 Surface Pressure-MMA isotherms and compressibility-MMA curves of the hydrosilylated (PB(Si(OEt)3)b -PEO)3 star block copolymer at various reaction times (subphase pH = 3.0).........................................................................................................117

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13 5-19 Isobars of the hydrosilylated (PB(Si(OEt)3)b -PEO)3 star block copolymer for various subphase pH values ( = 5 mN/m)......................................................................118 5-20 Removal of the cross-linked (PB(Si(OEt)3)b -PEO)3 three-arm star copolymer from the Langmuir trough surface............................................................................................119 5-21 AFM topographic images of the (PB(Si(OEt)3)b -PEO)3 star block copolymer LB films.......................................................................................................................... .......122 5-22 Cross-section analysis of Figures 5-21D and 5-21H, PEO pore size versus surface pressure plot, and PSD plots of Fi gures 5-21C, 5-21D, 5-21G, and 5-21H....................122 5-23 AFM topographic images and correspondi ng cross-sections of the (PB(Si(OEt)3)b PEO)3 star block copolymer LB films cross-linked at 9 mN/m (pH = 3.0, t = 10 h) and transferred at 9 and 2 mN/m......................................................................................123 5-24 Surface pressure-MMA isotherms of the hydrosilylat ed (PB(Si(OEt)3)b -PEO)3 star block copolymer cross-linked at 5 and 20 mN/m (pH = 3.0, t = 10 h)............................124 6-1 Oil-filled silica nanocapsule synthesi s through initial hydrophobic core formation followed by hydrophilic silica shell formation after TMOS addition..............................132 6-2 Description of the nanocapsule samp les prepared using 0.07, 0.28, 0.44, and 0.88 wt % TMOS......................................................................................................................... .132 6-3 DLS results for the microemulsion imme diately after preparation and the same solution after TMOS addition (0.07 wt %) and dialysis..................................................133 6-4 TEM micrographs of the 0.07 wt % TM OS nanocapsules and of the 0.88 wt % TMOS nanocapsules........................................................................................................134 6-5 Chemical structures of ferrocene metha nol, ferrocene dimethanol, and Nile Red..........135 6-6 UV-vis absorption spectra of iodine in water solution, in nano capsule solution, in Tween-80 aqueous solution, and in ethyl butyrate solution............................................136 6-7 Nile Red emission spectra in ethyl butyrate solution, in nanocapsule solution, in Tween-80 aqueous solution, in crushed Xer ogel dispersion in acidic water, on silica gel, and in acidic water solution......................................................................................137 6-8 Typical cyclic voltammogram of ferrocene methanol in water.......................................138 6-9 Uptake of ferrocene methanol versus time in 0.07, 0.28, 0.44, and 0.88 wt % TMOS nanocapsule solutions......................................................................................................141 6-10 Plot of normalized aqueous concentrati on of ferrocene methanol after uptake in 0.07, 0.28, 0.44, and 0.88 wt % TMOS nanocapsule solutions................................................142

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14 6-11 Uptake of ferrocene dimethanol versus time in 0.07, 0.28, 0.44, and 0.88 wt % TMOS nanocapsule solutions..........................................................................................144 6-12 Uptake of ferrocene methanol versus time in 0, 2, 4, 6, and 8 wt % Tween-80 aqueous solutions.............................................................................................................1 45 6-13 Uptake of ferrocene dimethanol versus time in 0, 2, 4, 6, and 8 wt % Tween-80 aqueous solutions.............................................................................................................1 46 7-1 Chemical structures of amitriptyline and bupivacaine.....................................................152 7-2 The molecular imprinting strate gy in miniemulsion polymerization..............................154 7-3 IR absorbance spectra of EGDMA, MIP1, and MIP3.......................................................155 7-4 DLS size distribution of MIP6..........................................................................................156 7-5 Tapping mode topographical AFM images and cross-section analysis of MIP6.............157 7-6 Uptake of amitriptyline by the non-mo lecularly imprinted nanoparticles MIP1, MIP2, and MIP3..........................................................................................................................158 7-7 Uptake of amitriptyline by the nano particles molecularly imprinted with amitriptyline: MIP4, MIP5, and MIP6...............................................................................159 7-8 Uptake of bupivacaine by the nanoparticles molecularly imprinted with amitriptyline: MIP4, MIP5, and MIP6...............................................................................160

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15 Abstract of Dissertation Pres ented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy TWO-DIMENSIONAL SELF-ASSEMBLY OF AMPHIPHILIC BLOCK COPOLYMERS AT THE AIR/WATER INTERFACE AND NANOPA RTICLES FOR DRUG DETOXIFICATION APPLICATIONS By Thomas J. Joncheray December 2006 Chair: Randolph S. Duran Major Department: Chemistry The two-dimensional self-assembly at the ai r/water (A/W) interface of various block copolymers (dendrimer-like polystyreneb -poly( tert -butylacrylate) (PSb -P t BA) and polystyreneb -poly(acrylic acid) (PSb -PAA), linear and five-arm star poly(ethylene oxide)b poly(-caprolactone) (PEOb -PCL), and three-arm star triethoxysilane-functionalized polybutadieneb -poly(ethylene oxide) (PB(Si(OEt)3)b -PEO)) was investigated through surface pressure measurements (isotherms, isobars, isochores, and compression-expansion hysteresis experiments) and atomic force microscopy (AFM) imaging. The PSb -P t BA and the PSb -PAA samples formed well-defined circular surface micelles at low surface pressures with low aggregation numbers (~ 3-5) compared to linear analogues before collapse of the P t BA chains and aqueous dissolution of the PAA segments ta ke place around 24 and 5 mN/m, respectively. The linear PEOb -PCL samples exhibited three phase transitions at 6.5, 10.5, and 13.5 mN/m corresponding respectively to PEO aqueous dissolution, PEO brush formation, and PCL crystallization. The two PEO pha se transitions were not obser ved for the star-shaped PEOb -PCL samples because of the negligible surface activity of the star-shaped PEO core compared to its linear analogue. The PB(Si(OEt)3)b -PEO sample was cross-linked at the A/W interface by self-

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16 condensation of the pendant triethoxysilane groups under acidic conditions, which resulted in the formation of a two-dimensional PB network cont aining PEO pores with controllable sizes. With a view toward drug detoxification ther apy, the encapsulation abilities of oil coresilica shell nanocapsules and molecularly imprinte d nanoparticles were al so investigated by electrochemical (cyclic voltamm etry) and optical (fluorescence and UV-vis spectroscopies) techniques. The core-shell nano capsules were shown to effici ently remove large amounts of organic molecules present in aqueous solutions, with the silica shell acting analogously to a chromatographing layer. The molecularly imprin ted nanoparticles were prepared by the noncovalent approach and by miniemulsion polym erization. Binding studies on the molecularly imprinted nanoparticles in aqueous solutions under physiological pH conditions indicated that, in the absence of specific imprinting, the uptake of toxic drugs was mainly driven by non-specific hydrophobic interactions. As demonstrated with the use of the antidepressan t amitriptyline, in the presence of specific imprinting the uptake significantly increas ed as the amount of specific binding sites was increased.

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17 CHAPTER 1 INTRODUCTION This dissertation aims at summarizing the work realized on two diffe rent research domains of polymer chemistry: the air/water (A/W) inte rfacial behavior of block copolymers and the synthesis of nanoparticles for drug detoxification applications. As presented in Chapters 3, 4, and 5, the first three research projects are rela ted to the self-assembly of amphiphilic block copolymers at the A/W interface, whereas Chapters 6 and 7 describe the investigations carried out on the possibility for 2 different types of nanoparticulate systems to be used as drug detoxification agents. While Chapter 2 briefly de scribes the principal experimental techniques mentioned in the subsequent chapters, this firs t introductory chapter serves as literature background for the different resear ch projects and also defines the key concepts used throughout this dissertation. 1.1 Block Copolymers in the Bulk and in Solution “Block copolymer” is a general term used to define a macromolecule composed of different polymer chains. The field of block copolym ers has attracted a lot of interest in the past thirty years because the eventual phase sepa ration between immiscible blocks in various environments, such as in the bulk, often leads to well-defined self-assembled structures with unique morphologies with characte ristic sizes ranging between a few nanometers up to hundreds of nanometers.1,2 Moreover, the recent emergence of c ontrolled polymeriza tion techniques such as living anionic polymerization,3 ATRP (atom transfer radical polymerization),4 or RAFT (reversible addition fragm entation chain transfer)5 has allowed access to a variety of compositions and architectures (star,6 mikto-arm,7 cyclic8. .), which signifi cantly increases the diversity of peculiar and regular patterns obtainable resulting from their self-assembly. A lot of research still has to be done to better understand the relations hips between block copolymer

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18 architecture and self-assembly. Th erefore, because of their simple architecture, linear diblock copolymers are still currently th e best-known class of block c opolymers. Several theoretical models have been proposed to desc ribe the behavior of block copol ymers such as fo r instance the self-consistent field theory (SCFT)9 or the mean-field theory (MFT)10 where the phase behavior is dictated by the Flory-Huggins segment-se gment interaction parameter, the degree of polymerization, and the composition. As an example, if the two A and B blocks of a linear AB diblock copolymer are immiscible, they can adop t in the bulk, as shown in Figure 1-1, various microphase morphologies such as spheres (S and SÂ’), cylinders (C and CÂ’), double gyroids (G and GÂ’), or lamellae (L).1c Figure 1-1. Mean-field pr edication of the morphologies for conformationally symmetric diblock melts. Phases are labeled as: S (spheres) C (cylinders), G (double gyroids), L (lamellae). f A is the volume fraction.1c When block copolymers are dissolved in a sele ctive solvent, the chai ns can aggregate to reversibly form well-defined micelles above the so -called critical micella r concentration (CMC). For concentrations lower than the CMC, bloc k copolymer molecules are unassociated as illustrated in Figure 1-2 for amphiphilic diblock c opolymers in water aggregating into spherical micelles.

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19 Figure 1-2. Solution state for amphiphilic diblock copolymers in water for concentrations below and above the CMC. The critical micellar con centrations of block copolymers ar e usually very low compared to low molecular weight surfactants, and therefore th e micelles formed have great potential in drug delivery when used as nanocontainers since they hardly dissociate in the blood stream, even under highly dilute conditions.1a Depending on the architecture, composition, concentration, or solvent, block copolymers can aggregate into a variety of micellar stru ctures. Figure 1-3 shows as an example some peculiar morphologies obta ined by Eisenberg and co-workers for “crew-cut” micelles of linear polystyreneb -poly(acrylic acid) (PSb -PAA) diblock copolymers in aqueous solutions.11 Transitions from spheres to rod to vesicl es were observed as the length of the PAA segment was decreased. In semi-dilute or concentrated solutions, gelation normally occurs, and block copolymer micelles organize into a nanostr ucture-ordered lyotropic liquid crystal phase.12

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20 Figure 1-3. Spherical (a), rodlike (b), and vesicular (c) morphologies for PSb -PAA crew-cut micelles.11 1.2 Block Copolymers at the A/W Interface The behavior of block copolymers at interfa ces is also of great interest since other parameters such as the surface energies as well as film thickness can strongly influence the microphase separation.1c Confining polymeric chains in a la yer thinner than their natural length scale (the radius of gyration) considerably a lters their conformation and the resulting physical properties compared to the bulk properties.13 Among the variety of surfaces and interfaces available, the A/W interface has attracted a lot of attention because it allows the easy formation of two-dimensional polymeric monolayers (Langmuir monolayers), providing that the block copolymers studied are surface active by having suffici ently polar functional gr oups to adsorb at the interface (without being too mu ch water soluble to avoid their irreversible dissolution in the aqueous subphase). Similarly as for low mol ecular weight surfactants, surface active block copolymers self-assemble at the A/W interface to reduce the surface tension (internal pressure caused by the attraction of mol ecules below the surface for thos e at the surface) with the hydrophilic segments immersed into the water and the hyd rophobic segments desorbed in the air as illustrated in Figure 1-4 for a low molecular weight fatty acid amphiphile.14

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21 Figure 1-4. A schematic illu stration showing the components of an amphiphile and the orientation of this amphiphile adopted at an interface.14 As previously shown, one of the great advantages of the A/W interface is that it is possible and fairly easy to accurately control and adjust the way the chains of the block copolymers selfassemble simply by varying thei r surface concentration (amount pr esent at the interface) in addition to the other usual parameters mentioned before for the bulk or for solutions. This often leads to peculiar arrangements of the polymer chains with the formation of surface micelles, which significantly differs from what is co mmonly observed for low molecular weight amphiphiles. Control of surface density in th e Langmuir films and transfer of the block copolymer monolayers onto solid substrates for fu rther analysis (Langmuir-Blodgett films) are experimental procedures commonly done with the use of a Langmuir trough as extensively described later in Chapter 2. A wide range of experimental techniques can be used for morphology investigation in Langmuir and Langmuir-Blodgett (LB) monolayers including neutron and X-ray reflectivity, surface pressure and potential measurements, Brewster angle microscopy (BAM), atomic for ce microscopy (AFM), transmi ssion electron microscopy (TEM), and ellipsometry.15-20 Examples of block copolymers with various architec tures previously

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22 studied at the A/W interface include poly(ethylene oxide)b -poly(propylene oxide) (PEOb PPO), polystyreneb -poly(ethylene oxide) (PSb -PEO), polybutadieneb -poly(ethylene oxide) (PBb -PEO), and polystyreneb -polyacrylate.21-24 Block copolymers based on PS and decylated poly(4-vinylpyridine) (decylated P4 VP) have also been extensively investigated at the A/W interface by Eisenberg and co-workers, and some of their results are presented here to illustrate the concept of surface micelle form ation. Surface micelle formation results from the presence at the A/W interface of immiscible blocks that phas e separate because of sufficiently different polarities. In the case of PS and decylated P4 VP-based block copolymers, only the hydrophilic decylated P4VP segments adsorb at the A/ W interface with the hy drophobic PS segments desorbing and aggregating above the interface. Th is results in the formation of well-defined surface micelles with architectures evolving from circ ular to rod-like to plan ar as the PS % in the diblock copolymers is increased (Figure 1-5).25 Prospective applications of such well-defined patterns with feature sizes typically in the na nometer scale order include lithographic masks, photonic materials, and nanopatterned substrates for microelectronics.26-28 The results presented in Chapters 3, 4, and 5 of this dissertation are all related to the selfassembly of block copolymers at the A/W interface. While the work presented in Chapters 3 (on polystyreneb -poly( tert -butylacrylate) and polystyreneb -poly(acrylic acid) dendrimer-like block copolymers) and 4 (on linear and st ar-shaped poly(ethylene oxide)b -poly( -caprolactone) block copolymers) describes the interf acial aggregation of several bl ock copolymers on a fundamental level, the work presented in Chapter 5 (on star-shaped poly(ethylene oxide)b -hydrosilylated polybutadiene block copolymers and done in coll aboration with Rachid Matmour, graduate student in the Duran group at the University of Florida) focuse s primarily on th e use of a post

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23 monolayer formation cross-linking method usi ng Sol-Gel chemistry (Section 1-5) for the synthesis of novel two-dimensional cross-linked nanomaterials with well-defined morphologies. Figure 1-5. Transmission elec tron micrographs of LB films of poly(styreneb -vinylpyridinium decyl iodide) AB diblock copolymers (surface pressure = 2 mN/m) (a) P(S260-bVP120/C10I); % PS = 68.4; (b) P(S260-b-VP71/C10I); % PS = 78.5; (C) P(S260-bVP29/C10I) % PS = 90 .0; (d) P(S480-b-VP34C10I) % PS = 93.4; (e) P(S180-b-VP11/C10I) % PS = 94.2; (f) P(S480-b-VP13/C10I) % PS = 97.4.25 1.3 Current Status of Drug Detoxification Therapy Drug toxicity is a major health concern, because more than 3 million insecticide poisonings are reported every year worldw ide with, among them, around 200,000 fatal cases.29 In the United States, a 2000-query showed that drug-related complications lead to the hospitalization of more than 300,000 patients per year. Ot her important issues ar e related to clinical mistreatment for instance in the area of anes thesiology where it was recently shown that the

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24 intravenous injections of local anesthetics such as bupivacain e are a major cause of cardiac blocks with a fatal outcome.30,31 Tricyclic antidepressants such as amitriptyline (one of the most common drugs used in suicides32) are among the most frequently ingested substances in selfpoisoning.33 Common clinical treatments in the case of anesthetic-induced toxicity include rapid oxygenation, ventilation, seizure co ntrol, and cardiovascular support.34 To fight drug overdose, several methods have been explored such as the intravenous injecti on of sodium bicarbonate,35 the use of activated carbon,36 the use of lipid infusions,37 or even the use of other drugs such as amiodarone,38 insulin,39 or propofol.40 All these methods have shown some interesting results but an efficient and specific antidote scavenging the toxicity of the aforem entioned antidepressant and anesthetic drugs by reducing their bio-availa bility within the body still has to be designed. 1.4 Nanoparticle Technology Living organisms are built of cells that are usually a few micrometers in size, and their organelles are even much smaller, in the sub-micron size range. The recent development of nanotechnologies that deal w ith nanometer-sized objects (n anoparticles) for instance in electronics, cosmetics, or catalysis41,42 also opened the possibility to probe the cellular machinery without introducing too much interference43 and to understand biolog ical processes on the nanoscale level.44 Recent developments of nanoparticulat e systems include for instance protein detection,45 tissue engineering,46 cancer therapy,47 and drug delivery.48 Because of the absence of specific antidotes in the case of drug intoxication as mentioned in the previous paragraph, a multidisciplinary effort is being made at the University of Florida (Particle Engineering Research Center and Departments of Chemistry, Mate rial Science, Chemical Engineering, and Anesthesiology) to synthesize a series of novel nano-sized bioparticles that are able to move freely in the blood stream even in th e smallest capillaries (diameter ~ 5 m) and that are able to

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25 effectively reduce the free blood concentration of toxic drugs. The ideal nanopart iculate system therefore should have high and fast (within seconds or minutes) encapsulat ion capacities, should be biocompatible (non-toxic), biodegradable (slo wly enough so the aqueous concentration of the drug released in the blood stays below toxic levels), and above al l, should be specific to the target drug to avoid side encapsulation of othe r undesired molecules present in the blood stream. Oil core-silica shell nanocapsules have been recently synthesized in the Duran group by combining microemulsion formulation and Sol-Gel chemistry,49 and with a view toward their application in detoxification media, the work presented in Chapter 6 focused on investigating their uptake kinetics and capacities of drug-mi micking compounds. In Chapter 7, a different and novel type of nanoparticles was synthesized and characterized by combining miniemulsion polymerization and molecular imprinting technol ogy in an attempt to de sign a nanoparticulate system with increased selectivity. 1.5 Microemulsions and Sol-Gel Chemistry A microemulsion is defined as a system comp rising oil, water, and surfactants (surface active agents having both a hydrop hilic part and a hydrophobic part ) that results in a singlephase, optically isotropic, and therefore thermodyna mically stable liquid so lution. This is not the case for emulsions that are usuall y only kinetically stab le and that coalesce and phase-separate over time. When water, oil, and surfactants ar e mixed together to form a microemulsion, the surfactant molecules rest at the oil-water interface with the h ydrophilic groups so lubilized into the aqueous phase and the hydrophobic groups solubi lized into the organic phase to avoid the direct oil-water contact. The sizes of these structures are usually in the range of a few hundred nanometers, which makes them suitable for the synthesis of nano-sized objects. Depending on several parameters such as the nature of the oil or of the surfactant and th e concentrations or the relative amounts of oil, surfactant, and water used, it is possible to obtain a variety of internal

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26 structures. They can be spherica l (Figure 1-6), spheroidal, or cylindrical “rod” or “worm-like” micelles, and they may exist in hexagonal, cubic, or lamellar phases. Alternatively, a range of bicontinuous phases may exist. Figure 1-6. Structure of norma l (left) and inverse (right) spherical micelles formed in microemulsion systems. Microemulsions can have characteristic propert ies such as ultra low interfacial tension, large interfacial area and capacity to sol ubilize both aqueous and oil-soluble compounds.50 Therefore, they can be used in a variety of a pplications, for example in enhanced oil recovery,51 as fuels,52 as lubricants, cutting oils and corrosion inhibitors,53 as coatings and textile finishing,54 in detergency,55 in cosmetics,56 in food,57 in pharmaceuticals,58 or in biotechnology.59 As presented in Chapter 6, an oil-in-water microe mulsion system composed of spherical micelles was designed in an attempt to selectively encapsulate hydrophobic toxic drugs inside the micellar oil core and to decrease their free concentration in the blood st ream. Even though microemulsion systems are thermodynamically stable, the high d ilution taking place after th eir injection inside body fluids would lead to rupture and further coalescence of the mice llar structures. This problem can be avoided by building a solid she ll surrounding the microemuls ion oil droplets that will not break upon dilution, for instance by the m eans of Sol-Gel chemistry (hence the name core-shell nanocapsules).

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27 The Sol-Gel process allows the easy synthesi s of ceramic and glass materials with high purities and homogeneities by usi ng preparation techniques different from the traditional process of fusion of oxides. This process occurs in liq uid solutions in the presence of organometallic precursors such as metal alkox ides (tetramethoxysilane, tetraet hoxysilane, Zr(IV)-propoxide, or Ti(IV)-butoxide), which, through acidor base-cat alyzed hydrolysis and condensation reactions as shown in Figure 1-7, leads to th e formation of a new phase (Sol).60 Figure 1-7. Sol-Gel hydrolysis and condensation reactions. The Sol is made of solid particles of a diam eter of a few hundred nanometers suspended in a liquid phase. The particles then condense in a new phase (Gel) in which a solid macromolecule is immersed in a liquid phase (solvent). Drying the Gel by means of low temperature treatments allows the formation of materials in a wide vari ety of forms: ultra-fine or spherical shaped powders, thin film coatings, ceramic fibers microporous inorganic membranes, monolithic ceramics and glasses, or extremely porous aerog el materials as illustrated in Figure 1-8.61 Sol-Gel materials can be used for instance in chemical sensing,62 drug delivery,63 or electrochromics.64 As further explained in Chapter 6, the formation of a rigid shell to im part stability to the microemulsion droplets resulting in the form ation of core-shell nanocapsules was done by polycondensation of tetramethoxysilane directly on the microemuls ion droplet surface previously functionalized with trimethoxysilane groups. A si milar polycondensation method was also used as presented in details in Chapter 5 to crosslink in two dimensions bl ock copolymers containing triethoxysilane-functionalized polybutadi ene segments at the A/W interface.

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28 Figure 1-8. Sol-Gel technol ogies and their products.61 1.6 Molecular Imprinting and Miniemulsion Polymerization The concept of molecularly imprinted polym ers (MIPs) was first introduced by Wulff nearly thirty years ago.65 Since then, the methodology has unde rgone a number of important developments, and MIPs have been used in a wi de range of techniques (i n solid-phase extraction, as biosensors, as catalysts, and as binding as says) and approaches (cova lent, non-covalent, metal coordination).66-72 MIPs result from the polymerization of monomeric units in the presence of a template molecule. The imprinting strategy investig ated in Chapter 7 is shown in Figure 1-9 and uses the non-covalent imprinting a pproach first developed by Mosbach.73,74 Functional monomers are associated with a template via non-covalent interactions. The complex is then copolymerized with a cross-linking monomer, followed by removal of the template using extraction procedures. Removal of the templa te results in cavities whose shape, size, functionality, and spatial arrangement are comp lementary to the imprinted molecule. These

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29 recognition sites with predetermine d selectivity enable MIPs to re bind selectively the original template from a mixture. In principle, MIPs can be made with selectivity for essentially any of a diverse range of analyte species, such as drug enantiomers, pesticides, hormones, toxins, short peptides, and nucleic acids.75-80 Figure 1-9. Outline of the molecular imprinting strategy. Many parameters can affect the efficiency of the synthetic molecularl y imprinted polymers such as the porogen (solvent), th e polymerization technique, and also the relative concentrations of the functional monomer, cross-linker, templa te molecule, and initiator. Figure 1-10 shows examples of classical functional monomers and cross-linkers comm ercially available for radical polymerization.81 Functional monomers Crosslinkers Figure 1-10. Examples of commercially ava ilable functional monomers and cross-linkers.81

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30 The main motivation to investigate the poten tial of molecularly imprinted materials for drug detoxification applications was to harvest th eir remarkable ability to rebind specifically a variety of compounds including toxic drugs. As described later in fu rther details (Chapter 7), the synthesis of nano-sized molecularly imprinted particles was attempted through miniemulsion radical polymerization, and their toxic dr ug-rebinding capacities were investigated. Miniemulsions are produced by the combination of a high shear to brea k up the emulsion into submicron monomer droplets and a surfactant/costabilizer system to retard monomer diffusion from the submicron monomer droplets.82 The costabilizer is used to prevent Ostwald ripening.83 Compared to microemulsions that usually lead to the formation of oil droplets ranging from 10 to 100 nm, the formation of miniemulsions, which re quires a lower amount of surfactants, usually leads to oil droplet diameters ranging from 50 to 500 nm. The droplet surface area in these systems is very large, and most of the surfactants are adsorbed at the droplet surface. Since little surfactant is present in the form of micelles in a properly formulated microemulsion, particle nucleation during polymerization primarily takes place inside the monomer droplets. This leads to a 1:1 correspondence between the initial monomer droplets and the final polymer nanoparticles. The principal of miniemulsion polymerization is sc hematically shown in Figure 111. As described in greater details in Chapte r 7, the synthesis of molecularly imprinted nanoparticles was done radically, bu t the miniemulsion polymerizati on process is not limited to radical polymerizations.84-86 The imprinting takes place insi de the monomer droplets, and extraction of the toxic drug molecules results in porous nanoparticles with recognition sites complementary in shape to the original toxic drug template.

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31 Figure 1-11. Principal of miniemulsion polymerization.

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32 CHAPTER 2 EXPERIMENTAL TECHNIQUES In this chapter, an overview of the princi pal experimental techniques is presented. The specific detailed experimental procedures are not described here but are included instead at the end of each of the following chapters in the Experimental sections. 2.1 Langmuir Monolayers and Surfa ce Pressure Related Experiments As further detailed in Chapters 3, 4, and 5, investigation of block copolymer self-assembly at the air/water (A/W) interface in Langmuir monolayers requires the use of a Langmuir trough. A typical set-up is shown in Fi gure 2-1. It provides a very simp le method to control monolayer surface density thanks to the movable barriers controlled by a DC motor. The trough is composed of an inert material such as for inst ance Teflon (polytetrafluoroe thylene, PTFE) that is resistant to water absorption. Figure 2-1. The Langmuir Teflon trough. To form a Langmuir monolayer, the block copolym er of interest is first dissolved in a solvent (C 1mg/mL) which is then spread dropwise on the water surface. The solvent must be hydrophobic to prevent its dissolution in the wate r subphase and so it doesnÂ’t influence the surface pressure measurements. It should be also volatile enough to quickly evaporate from the surface after spreading, leaving behind the adso rbed block copolymer molecules. Chloroform was the solvent of choice in this dissertation ex cept in Chapter 2 where the use of a more polar

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33 chloroform/ethanol mixture was nece ssary to dissolve the polystyreneb -poly(acrylic acid) dendrimer-like block copolymer sample. Other commonly used solvents include n-hexane, benzene, diethyl ether, as well as mixtures such as for instan ce hexane-ethanol, benzene-ethanol, or chloroform-methanol.87 After spreading, the surface active block copolymers expand to form an adsorbed monolayer that quic kly covers the entire av ailable area present between the barriers. In addition to the A/W interface which is the most commonly studied interface, others are possible such as oil/water interfaces or ga s (different from air)/water interfaces. Figure 2-2. A Wilhelmy plate partia lly immersed in a water subphase. The surface pressure measurements were achie ved by use of the Wilhelmy plate technique as shown in Figure 2-2.87 The surface tension () is defined by Equation 2-1, 0 (2-1) where 0 represents the surface tensi on of the water subphase in the absence of an adsorbed monolayer, and represents the surface tension of the water subphase in the presence of an adsorbed monolayer. Water is a very interestin g subphase when investig ating monolayers since it has an exceptionally high surface tension ( 73 mN/m at 20 oC and under atmospheric pressure87) that allows a wide range of surface pre ssures to be obtained. When the Wilhelmy plate is partially immersed into the subphase, th e forces acting consist of gravity and surface

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34 tension downward as well as an upward buoyancy due to displaced water. The resulting force F is monitored and related to the surface tension as shown in Equation 2-2: ghwt w t glwt Fs p cos ) ( 2 (2-2) where p and s correspond to the densities of the Wilh elmy plate and the subphase, respectively, g corresponds to the gravitational constant, t (thickness), w (width), and l (length) are the dimensions of the Wilhelmy plate, is the contact angle made by the subphase onto the plate ( = 0 for a completely wetted plate, cos = 1), and h corresponds to the plate height immersed into the subphase. When measuring the change in F ( F ) for a stationary plate after formation of an adsorbed Langmuir monolayer, assuming that t is negligible compared to w the equation can be reduced to: w F 2 (2-3) and therefore, the surface pressure is directly related to the cha nge in force and the width of the plate: w F 2 (2-4) With the Wilhelmy plate technique, the sensitivity can be as low as 5x10-3 mN/m. Nevertheless, since very small amounts of im purities can affect surface pre ssure measurements, the water subphase consists of Millipore filtered wate r with resistivities greater than 18.2 M .cm. Moreover, the trough needs to be carefully cleane d for instance with ethanol before forming a Langmuir monolayer and rinsed several times with Millipore filtered water. Contamination with impurities coming from the air can also be minimized by covering the trough or by carrying out the experiments in a clean room. The subphase temperature can also be regulated with a circulating water bath.

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35 Once a Langmuir monolayer is formed at the A/W interface, a variety of surface pressure related experiments are possible. The simplest e xperiment is the isotherm, where the monolayer is compressed toward the center of the trough and the surface pressure reco rded versus surface density or mean molecular area (MMA, average area occupied by one molecule at the interface, calculated from Equation 2-5). A nCVN AM MMA (2-5) A is the area between the barriers, Mn is the molecular weight of the sample, NA is the AvogadroÂ’s number, and C and V are the concentration and the volume of the spreading solution, respectively. Upon compression, the adsorbed molecules move closer to one another, the surface pressure increases, and the phase transitions taki ng place in the monolayer are characterized by pseudoplateaus or inflection points in the su rface pressure versus MMA (or surface density) isothermal plot as exemplified in Figure 2-3 for small amphiphilic molecules. The monolayer undergoes phase transitions from th e gaseous state (G) to the liqui d state (L) and eventually to the solid state (S) upon high compression. Figure 2-3. Schematic isotherm for small amphiphilic molecules.14

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36 Other possible experiments include compre ssion-expansion hystere sis, isobaric, or isochoric experiments. In the hy steresis experiment, the barriers compress the monolayer up to a target surface pressure (or target MMA) and expand several times. In the isobaric experiment, the monolayer is compressed up to a desired su rface pressure which is then kept constant by small barriers adjustments, and the evolution of the MMA versus time is recorded. In the isochoric experiment, the barriers are stopped after reaching the desired surface pressure (or MMA), and the surface pressure ev olution is subsequently record ed versus time. These last 3 experiments are usually used to investigate monolayer stability versus time or its formation reversibility as further exemplifie d in Chapters 3, 4, and 5. 2.2 Langmuir-Blodgett Films a nd Atomic Force Microscopy One of the interesting propertie s of the Langmuir trough is th at it is easy to transfer a Langmuir monolayer prepared at the A/W interf ace onto a solid substrate for further analysis. The most common technique for monolayer transfer is done by vertic ally lifting a substrate into a Langmuir monolayer compressed at the desired surf ace pressure which is kept constant by small barrier adjustments (Figure 2-4) The resulting transferred film is called a Langmuir-Blodgett (LB) monolayer. The substrate used in this dissertation is freshly cleaved hydrophilic mica because it mimics the water subphase during transf er. It is also possible to prepare LB films consisting of multilayers by successively transferring several monolayers. This technique provides thin films of supramolecular assembli es with well-defined molecular arrangement,88 chemical composition, and thickness, and with fewer defects than if prepared directly from the bulk. The transfer ratio measures the degree of monolayer tran sfer. During LB monolayer formation, part of the molecules initially adsorb ed at the A/W interface are slowly transferred onto the substrate, which results in a lower surf ace density in the Langmuir monolayer. To keep

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37 the surface pressure constant du ring transfer (and therefore the surface density), the barriers have to move closer together which therefore reduces the available area betw een them. The transfer ratio can be subsequently directly calculated by dividing this decrease in surface area between the barriers by the total surface area of the substrate. Transfer ratio values smaller or larger than unity indicate that the packing of the transferred molecules is less or more dense than at the A/W interface, respectively. Substrate (mica) Wilhelmyplate Barrier Water Barrier Figure 2-4. LB film transfer onto a hydrophilic mica substrate. The experimental technique used in this di ssertation to examine the morphology of the LB films in Chapters 3, 4, and 5 is atomic force microscopy (A FM). This technique provides a topographical map of the LB films by scanning thei r surfaces with a sharp tip attached at the end of a flexible cantilever which is deflected as it moves up and down m ountains and valleys. A laser is reflected off the end of the cantilever and the deflection (meas ured by a photodiode) is converted into a topographical image with a resolution of 0.1 nm accuracy. Contact and noncontact AFM modes were first designed, but while in the contact mode soft samples can be distorted, in the non-contact mode the tip can easily become stuc k in the water layer covering the

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38 surface of samples exposed to the atmosphere. The AFM tapping mode used in this dissertation overcomes these problems. The tip is vibrated with sufficient energy to overcome the surface tension of the contaminant water layer, and this vibration also prevents frictional forces from dragging the sample, which is cr ucial when working with soft polymeric samples. The tapping mode electronic setup is shown in Figure 2-5. As scanning occurs in three dimensions, the scanner tube contains three piezo electrodes (a piezoelectric material is a substance that proportionally contracts and expands depending on an applied voltage) for the X Y, and Z directions. In addition to its convenience in ch aracterizing LB monolayer s, AFM was also used to image the molecularly imprin ted nanoparticles after their depos ition onto mica substrates as further described in Chapter 7. Figure 2-5. The AFM tappi ng mode electronic setup.89

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39 2.3 Transmission Electron Microscopy and Quasi-Elastic Light Scattering Transmission electron microsc opy (TEM) and quasi-elastic li ght scattering (QELS) were used in Chapters 6 and 7 to determine the shap e and size of the core-shell nanocapsules and of the molecularly imprinted nanoparticles. Electron microscopes use a beam of highly energetic electrons to examine objects on a very fine scale and can yield information such as sample topography, morphology, composition, or crystallinity.90 The electron source first forms a beam of electrons that ar e accelerated toward the specimen with a positive electrical potential. The beam is focused onto the sample, and various interactions can occur inside the irradiat ed sample, affecting the electron beam as shown in Figure 2-6. Figure 2-6. Specimen interac tions in electron microscopy.90 The electrons of inte rest in TEM are only the unscattere d electrons, even though the other types of electrons can be of interest for ot her applications. These unscattered electrons are

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40 transmitted through the thin sample without any interaction occurring inside the sample. The thicker areas will have fewer transmitted unscattered electrons and will therefore appear darker than the thinner areas. The unscattered electrons strike a screen where light is generated, allowing the user to see the sample image. Stai ning agents such as osmium tetroxide, ruthenium tetroxide, or uranyl acetate can also be used to increase the contrast of thin samples that do not sufficiently scatter the electron beam. Quasi elastic light scattering (QELS, also calle d dynamic light scattering, DLS) is used to determine the hydrodynamic radius or diameter of nano-sized particles susp ended in a solution. These particles are subject to Brownian motion, with small particles diffusing faster than large particles according to the Stokes-Einstein equation (2-6 ) relating diffusion coefficient ( D ) and particle radius ( R ): R T k DB6 (2-6) where kB is the Boltzmann constant, T is the temperature, and is the solution viscosity. A beam of laser light is first focused on the sample, the particles scatter the incoming light in all directions, and the scattered phot ons are measured by a photomultiplier tube. The time variation of the scattered intensity is then analyzed with a digital correlator used to compute the following autocorrelation function C() : B Ae C 2) ( (2-7) where A and B are instrumental constants. The diffusion coefficient D is then determined from the following 2 equations: ) 2 sin( 4 n q (2-8)

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41 2q D (2-9) where q is the scattering vector, n is the refracting index, is the scattering angle, is the laser wavelength, and the part icle hydrodynamic radius R is calculated from Equation 2-6. Each monodisperse population of particle sizes pro duces its own unique autocorrelation function (exponential decay). Mixtures of more than on e size population produce sums of exponentials, and therefore available algorithms can be used to extract “true” size dist ributions from complex samples.91 2.4 Cyclic Voltammetry Cyclic voltammetry was used in Chapter 6 to monitor the uptake versus time of hydrophobic electrochemical probes inside the oil-core of the core-shell nanocapsules. In cyclic voltammetry, the potential of a working electrode is continuously changed as a linear function of time, with the rate of change of potential refe rred to as the scan rate The potential is first scanned in one direction and then reversed at the end of the firs t scan. The advantage of such a technique in electrochemistry is that the produc t of the electron transfer that occurred in the forward scan can be probed again in the reverse scan. Figure 2-7 shows the basic shape of the current response for a cyclic voltammetry experi ment. The bulk solution first contains only the reduced form of the redox couple, so for potential s (in A) lower than the redox potential, there is no net conversion of the reduced form into the oxidized form. As the potential is increased toward the redox potential, a ne t anodic current appears and in creases exponentially. As the reduced form is oxidized, concentration grad ients appear, and diffu sion occurs down these gradients. At point B (anodic peak) and beyond, th e potential is sufficiently high so the reduced species reaching the electrode ar e immediately oxidized, and the current therefore now depends upon the rate of mass transfer which results in an as ymmetric peak shape. In C, the potential is

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42 reversed (decreased), and the current continues to decay. As the redox potential is approached, a net reduction of the oxidized species takes plac e resulting in the appearance of a peak-shaped cathodic current (D). Figure 2-7. Basic shape of the current res ponse for a cyclic voltammetry experiment.92 In the presence of a reversible redox system, that is for fast electron transfer processes at the electrode (reaction kinetics fast compared to th e scan rate), the surface concentrations of the oxidized and the reduced species are maintained at the values required by the Nernst equation (210): ) ln(r o oC C nF RT E E (2-10) where E is the electrode potential, Eo is the standard poten tial of the redox couple, R is the universal gas constant (8.314510 J K-1 mol-1), T is the temperature in K, n is the number of electrons transferred in the half reaction, F is the Faraday constant (9.6485309x104 C mol-1), and

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43 Co and Cr represent the surface concentr ations of the oxidized and re duced species, respectively. The peak potential separation ( Epa-Epc ) is equal to 57/ n the peak width is equal to 28.5/n, the peak current ratio ( Ipa / Ipc ) is equal to unity, and finally the faradaic current ( Ip ) is given by the following Randles-Sevcik equation (2-11): C AD n Ip2 / 1 2 / 1 2 / 3 510 69 2 (2-11) where A is the electrode area (cm2), D is the diffusion coefficient of the electroactive species (cm2/s), is the scan rate (V/s), and C is the bulk concentration of the electroactive species (mol/cm3). If A and are kept constant during successive cy clic voltammetry scans, a decrease in the bulk concentration of the electroactive spec ies can be simply measured by monitoring the decrease in the Faradaic current Ip This strategy was applied as further discussed in Chapter 6 to measure the encapsulation abilities and kinetics of two electrochemical probes with reversible electrochemical activities (ferrocene methanol and ferrocene dimethanol) inside the oil coresilica shell nanocapsules.

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44 CHAPTER 3 POLYSTYRENEb -POLY( TERT -BUTYLACRYLATE) AND POLYSTYRENEb POLY(ACRYLIC ACID) DENDRIMER-LIKE COPOLYMERS: TWO-DIMENSIONAL SELF-ASSEMBLY AT THE AIR-WATER INTERFACE 3.1 Introduction As introduced in Chapter 1, block copolymers are of great interest for nanotechnological applications because of th eir potential in forming well-defined morphologies in bulk,93 in solution,94 or at interfaces.95 Amphiphilic block copolymers offer good opportunities to control interfacial properties, and si nce they self-assemble at hydr ophilic/hydrophobic environments such as the air/water (A/W) inte rface to form regular arrangemen ts of two-dimensional surface micelles, they are particularly interesting as pr ecursors for the synthesis of well-defined patterns with feature sizes typically in the nanometer scal e order. The nanosized structures can be easily controlled by varying various parameters such as the nature of the blocks, the molecular weight, the relative lengths of the blocks, or even the bl ock copolymer architecture. With a view toward understanding the relationships be tween polymer architecture and A/ W interfacial aggregation, a variety of polystyreneb -poly(ethylene oxide) block copolymers with simple and complex architectures (linear, star-shaped, mikto-arm, dendrimer-likeÂ…) has been synthesized and extensively investigated in the past few years.22,96 Concerning polystyreneb -poly( tert -butylacrylate) (PSb -P t BA) and polystyreneb poly(acrylic acid) (PSb -PAA) block copolymers, only little work has been reported on their A/W interfacial behavior. Lennox a nd co-workers were to our knowle dge the only ones to report on the two-dimensional surface micelle formation for PSb -P t BA block copolymers, investigating linear samples with relatively small P t BA chains compared to the PS block.24,97 The self-assembly of PSb -PAA block copolymers was also studied almost exclusively for linear samples,20,98 and it is only very recently that Tsukruk and co-workers described the self-assembly

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45 of a twelve-arm heteroarm star copolymer w ith alternating PS and PAA arms at the A/W interface.99 In a recent publication, we described the synthesis of a variety of dendrimer-like copolymers based on polystyrene and poly( tert -butylacrylate) or poly (acrylic acid), and a preliminary investigation of their surface prope rties confirmed that such systems are ideal candidates for the synthesis of Langmuir and Langmuir-Blodgett (LB) monolayers with welldefined morphologies.100 In this chapter, we study th e A/W interfacial behavior of two dendrimer-like copolymers composed of an eight-arm star polys tyrene core with a sixteen-arm poly (tert -butylacrylate) or poly(acrylic acid) corona (Figure 3-1) by surfac e pressure measurements (isotherms, isochores, and compression-expansion hysteresis experime nts) and atomic force microscopy (AFM) imaging. Among the different dendrimer-like c opolymer samples previously synthesized, we deliberately chose to focus here on these 2 sample s since they have the largest number of arms and the largest P t BA (or PAA) weight %. These polymers are significantly different from the block copolymers studied in the previous literature in terms of architecture and chain length ratio, which should therefore lead to an in teresting and peculiar interfacial behavior. Figure 3-1. Schematic sketch of the PSb -PtBA (Dend1) and the PSb -PAA (Dend2) samples.

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46 3.2 Results and Discussion 3.2.1 PSb -P t BA Dendrimer-Like Copolymer (Dend1) The isotherm of Dend1 is pres ented in Figure 3-2, and the in set shows the static elastic modulus plot (s, Equation 3-1) versus surface pressure.101 ) ( ) ( MMA d d MMAs (3-1) The surface pressure in the isotherm increases in the high MMA region with a behavior characteristic of liquid expa nded and liquid condensed phases until a plateau suggesting a biphasic state is observed at 24 mN/m. Upon fu rther compression in the low MMA region, the pressure sharply increases up to va lues as high as 70 mN/m. PS and P t BA are two hydrophobic polymers, but contrary to PS, the presen ce of slightly polar ester groups in P t BA allows the adsorption of P t BA homopolymers and P t BA-based block copolymers at the A/W interface. The isotherm of Dend1 is very similar in shape to the isotherms of P t BA homopolymers, with only one phase transition observed at 24 mN/m.102 Moreover, the extrapolatio n of the linear portion of the isotherm below the plat eau to zero pressure ( Apancake)103 yields a value of 29 2 per P t BA repeat unit, which is in good agreement w ith the previously reported literature.104 These two observations indicate that Dend1 behaves similarly in te rms of surface activity to P t BA homopolymers, with the PS blocks desorbed in the air on top of the adsorbed P t BA blocks. Nevertheless, these results are significantly different from those obtained by Lennox and coworkers for linear PSb -P t BA diblock copolymers with relatively low P t BA wt %.24,97 They showed that the presence of the PS block induc ed two additional phase transitions of the P t BA block below 20 mN/m and suggested that these tr ansitions might originat e from the peculiar surface aggregation into circular micelles. As s hown in the inset of Figure 3-2, only one local minimum characteristic of a phase transition is observed at 24 mN/m for the static elastic

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47 modulus versus surface pressure plot. Moreover, Dend1 also aggregates into spherical surface micelles (Figure 3-3). This indicates that in the ca se of circular surface micelles, the extra phase transitions are observable only for small P t BA chain length over PS chai n length ratios (high PS wt %). In the case of Dend1, we believe these tran sitions might be present but cannot be detected since they involve only the small amount of P t BA repeat units present in the vicinity of the PS micellar core, with the majority of the P t BA repeat units being too far and behaving similarly as in P t BA homopolymers. Figure 3-2. Isotherm of Dend1. (Inset) Static elastic modulus plot versus surface pressure. The AFM images of the LB films transferred below the plateau at 5, 10, 15, and 20 mN/m (Figures 3-3a, 3-3b, 3-3c, and 3-3d) show the circular micellar aggregation of Dend1 mentioned before with the bright circular domains corre sponding to the desorbed PS cores (~ 1-1.5 nm thick) and the darker background corresponding to the adsorbed P t BA chains. Estimation of the number of Dend1 molecules per circul ar micelle by the total area method105 yielded an average

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48 aggregation number of 3, independent of the surface pressure. PS has a high glass transition temperature (Tg ~ 100 oC for high molecular weight PS),106 and therefore, once a surface micelle has formed during the solvent spreading process, the micellar cores come closer to each other during compression but the aggregation number re mains unchanged with the chains stuck within a particular micelle (the temperat ure of the experiment is well below the Tg of the desorbed PS cores). Compression-expansion hysteresis experi ments were carried out with target surface pressures below the plateau and all the compressi on and expansion curves overlapped, which is indicative of film formation reproducibility and thermodynamic stability. AFM imaging of the LB films prepared during the second compression step of the hysteresis experiment did not reveal any significant difference compared to th e LB films formed during the first compression. The aggregation number is much smaller than the value of 95 block copolymers per circular surface micelle reported by Lennox and co-workers for a linear PS305b -P t BA222 diblock copolymer,97 which was expected based on the previous studies investigating the relationship between aggregation number and block copolymer architecture. For instance, increasing the wt % of the adsorbed PEO segment in linear PSb -PEO diblock copolymers resulted in a lower aggregation number.96c Even lower aggregation nu mbers were observed for PSb -PEO three-arm stars with a PEO corona compared to the linea r analogues or compared to the reverse star architecture with a PS corona.22 Similarly to these examples, the adsorbed P t BA chains of Dend1 are present in the corona and are approximately 10 times longer than the desorbed PS chains. Moreover, the large number of arms connected to the central calix[8]arene core and the dendrimer-like structure with 2 P t BA chains attached at the end of each PS arm also heavily favor the formation of highly curved interfaces,96f therefore also considerably reducing the aggregation number.

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49 Figure 3-3. Topographic AFM images of Dend1 LB films transferred at 5 (a), 10 (b), 15 (c), 20 (d), 24 (middle of plateau, MMA = 20,000 2, e and f), and 40 mN/m (g and h). A LB film of Dend1 was also transferred in the middle of the plateau (MMA = 20,000 2), and the resulting AFM images are shown in Figures 3-3e and 3-3f. In this case, no transfer ratio could be calculated since the ba rriers were manually stopped afte r compression before transfer, and therefore these two AFM imag es only qualitatively reflect th e A/W interfacial aggregation. Nevertheless, the images clearly confirm the bipha sic state of the plateau, with areas exhibiting circular surface micelles similarly as for lowe r pressures and other areas with aggregated domains significantly thicker (~ 3 nm) than the PS micellar cores. It wa s previously suggested that at the beginning of the plateau region, the tert -butyl groups reorient from prone to vertical, with further compression leading to film collapse.107 Since P t BA is a hydrophobic polymer, it collapses by aggregating on top of the water su rface. The aggregated areas observed in Figures 3-3e and 3-3f therefore likely correspond to desorbed Dend1 mono or multilayers. Compressionexpansion hysteresis experiments (3 cycles) we re carried out in the plateau region, and the resulting curves are sh own in Figure 3-4. All the compre ssion curves closely overlapped, indicating that the collapsed films are able to go back to their original adsorbed monolayer state

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50 upon barrier expansion. AFM imaging of the LB films transferred during the second compression at a surface pressure of 20 mN/m c onfirmed the presence of adsorbed and circular surface micelles and the absence of collapsed do mains. Nevertheless, a drop in pressure is observed during barrier expansion. Faster barrier speeds increased the pressure drop, which suggests that the readsorption kinetics of the collapsed P t BA segments are slower than the barrier expansion speed. Figure 3-4. Compression-expansion hystere sis plot of Dend1 (target MMA = 20,000 2). Further compression in the low MMA region l eads to a sharp surface pressure increase. The films formed in this region of the isotherm should be unstable since the surface pressure is higher than the P t BA collapse pressure of 24 mN/m. This was checked by carrying out isochoric experiments. A typical isochore after compression up to 40 mN/m is shown in Figure 3-5. The surface pressure undergoes a sudde n drop within the first seconds of the experiment before leveling off after a few minutes around 24 mN/m. It is not clear to us whether the sharp surface pressure increase upon high compression in the isot herm originates from interactions between the collapsed and desorbed aggregates formed in the plateau region or between eventual remaining adsorbed P t BA segments. In any case, the isochoric experiments confirmed that the

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51 films formed above the plateau are not thermod ynamically stable and relax within minutes down to the plateau surface pressure of 24 mN/m, which can be also s een as the equilibrium spreading pressure of the P t BA blocks. Compression-expansion hysteresi s experiments (3 cycles) were also carried out in this high surface pressure region, a nd an example for a target pressure of 40 mN/m is shown in Figure 3-6. The results are essentia lly similar to the hystere sis experiments carried out in the middle of the plateau, with the co mpression curves overlapping each other, and the expansion curves exhibiting a drop in pressure th at corresponds to the slow readsorption of the collapsed P t BA chains. AFM imaging of the LB films transferred during the second compression at a surface pressure of 20 mN/m also confirmed here the presence of circular surface micelles only. The morphology of the LB film transferred at 40 mN/m is shown in Figures 3-3g and 3-3h, and aggregated domains in additi on to the circular surface micelles are observed similarly as within the plateau. Nevertheless, the transfer ra tio was in this case significantly smaller than one (~ 0.25), which indicates that the film underw ent non-negligible expa nsion during transfer, suggesting that the density of desorbed aggregat es on the water surface is significantly greater than as shown in Figures 3-3g and 3-3h. Figure 3-5. Surface pressure/time isochoric rela xation plot of Dend1 after compression up to 40 mN/m.

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52 Figure 3-6. Compression-expansio n hysteresis plot of Dend1 (target pressure = 40 mN/m). 3.2.2 PSb -PAA Dendrimer-Like Copolymer (Dend2) As a preliminary study, we investigated the behavior of a PAA homopolymer (PAA250K), since to our knowledge no informati on is available in the previous literature on the Langmuir and LB monolayers of PAA homopolymers. PAA250K could not be dissolved in chloroform, so a chloroform/ethanol mixture (1/2 in volume) was us ed instead as the spreading solvent. PAA is a weak acid (pKa ~ 5.5),108 and its degree of ionization and c onsequently its surface activity are therefore strongly pH dependent. Under basic co nditions (pH = 11), the acid groups of PAA are deprotonated, and stable Langmuir monolayers of PAA250K could not be pr epared, with the surface pressure remaining close to 0 mN/m dur ing barrier compression. When ionized, PAA is not surface active109 and irreversibly dissolves into the aqueous subphase. Under acidic conditions (pH = 2.5), the aci d groups of PAA are protonate d, the chains become less hydrophilic and surface active, and therefor e stable Langmuir monolayers of PAA250K could now be prepared. The resulting isotherm is shown in Figure 3-7. The su rface pressure slowly increases in the high MMA region before a plateau is reached with the su rface pressure leveling

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53 off around 3.5 mN/m. In the high MMA region, the surface pressure increases with a behavior characteristic of liquid expanded an d liquid condensed phases, and PAA250K is likely adsorbed in a pancake conformation. The AFM image shown in Figure 3-8a ( = 1.5 mN/m) confirmed the presence of a pre tty homogeneous PAA250K LB film with the randomly distributed darker holes possibly forming after transfer as the PAA chai ns un-swell (dehydrate) during the drying step. PAA in its protonated form is surface active but it is still highly water soluble, and it has been previously shown for aqueous solutions of prot onated PAA that the surface pressure reaches a maximum, for instance around 3 mN/m for a molecular weight similar to PAA250K.109a This value correlates well with the plateau surface pressure, which indicates that, at this pressure, PAA250K desorbs from the interface and aggregates insi de the water subphase. Th e AFM images obtained for the LB films transferred at 3 and 3.5 mN/m ar e shown in Figures 3-8b and 3-8c, respectively. As the films are compressed within the plateau re gion, more and more desorbed aggregates (~ 35 nm thick) are observed. This indicates that when the PAA chains collapse by dissolving into the water subphase, they stay in the vicinity of the interface, probably re maining anchored by some adsorbed acrylic acid repeat uni ts that have not collapsed yet. Figure 3-7. Isotherm of PAA250K (pH = 2.5).

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54 Figure 3-8. Topographic AFM images of PAA250K LB films transferred at 1.5 (a), 3 (b), and 3.5 mN/m (c). The spreading solutions of Dend2 were prepared by using the same solvent mixture as for PAA250K (chloroform/ethanol mixture, 1/2 in volume). Similarly as for PAA250K, no stable Langmuir monolayers could be fo rmed for Dend2 under basic condi tions with its irreversible dissolution in the aqueous subphase. Contrary to the other PSb -PAA systems reported in the previous literature,20,98,99 the PS wt % in Dend2 is too low to allo w it to act as an anchor and thus preventing the dendrimer-like aqueous dissolution Nevertheless, under acidic conditions (pH = 2.5), the PAA segments of Dend2 are now protonated, and, similarly as for PAA250K, Dend2 becomes surface active. The resulting isotherm is shown in Figure 3-9, and the inset shows the monolayer compressibility plot ( K Equation 3-2) versus surface pressure.96g ) ( ) ( 1 1 d MMA d MMA Ks (3-2) In the high MMA region, the surface pressure sl owly increases before reaching a pseudoplateau around 5 mN/m (maximum in monolayer compressibil ity as seen in the in set of Figure 3-9) and sharply increasing under high compression up to approximately 10 mN/m. A pseudoplateau was already observed in the previous literature by Cu rrie et al. only for long PAA chains in linear PSb -PAA systems under acidic conditions, where they demonstrated by surface pressure and ellipsometry measurements the presence of a pa ncake-to-brush transition in the pseudoplateau

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55 region with the PAA segments di ssolving into the water subphase.20 It is not very clear at this point why the pseudoplateau surface pressure is a little bit higher for Dend2 (5 mN/m) compared to the PSb -PAA copolymers studied by Currie et al. or compared to PAA250K (3-4 mN/m). It might simply be a PAA chain length dependence, or possibly a peculiar influence of the dendrimer-like architecture. Figure 3-9. Isotherm of Dend2 (pH = 2.5). (Inset) Compressibility plot versus surface pressure. We investigated here the morphological evol ution by AFM imaging as the Langmuir films of Dend2 are compressed, and the resulting images of the LB films are shown in Figure 3-10. At low surface pressure ( = 2 mN/m, Figure 3-10a), Dend2 a ggregates into spherical surface micelles with bright PS cores (~ 1 nm thick) and a darker background co rresponding to the PAA blocks adsorbed in a pancake conformati on similarly as in Figure 3-8a for PAA250K. The average aggregation number was estimate d around 5 by the total area method.105 Such a low value can be

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56 rationalized similarly as for Dend1, with the long PAA chains present in the corona, the dendrimer-like shape, and the large number of ar ms emanating from the central calix[8]arene core all heavily favoring the formation of highly curved interfaces. The images shown in figures 3-10b through 3-10j were record ed for surface pressures within the pseudoplateau and ranging from 4 to 8 mN/m. As the films are compressed, the PAA segments progressi vely dissolve in the aqueous subphase, underneath the PS cores of the surface micelles that aggr egate into larger and thicker (~ 2 nm) domains. At the end of th e pseudoplateau, in the region where the surface pressure sharply increases unde r high monolayer compression ( = 8 mN/m, Figures 3-10k and 3-10l), all the PAA chains have desorbed in the water subphase and st retch to form a brush underneath the aggregated PS cores. Contrary to the hydrophobic P t BA segments of Dend1 that collapsed above the A/W interface, the hydrophili c PAA segments of Dend2 anchored by the PS segments dissolve into the water subphase. Comp ression-expansion hysteres is experiments were also conducted within the pseudoplateau region (target pressu re = 5 mN/m), and the results are presented in Figure 3-11. Very little hysteresis is observed with the ps eudoplateau still present after numerous cycles, which means that the desorb ed PAA segments can return to their original adsorbed state at low pressure after monolayer decompression. Th is was verified by transferring a LB film at 2 mN/m during the second compression cycle, and AFM imaging revealed the presence of circular surface micelles with no a ggregated domains. We do not have yet at this point enough experimental evidence to rationali ze the small hysteresis shift, but it could for instance come from some entanglement of the PAA chains during the pancake-to-brush transition or from a different arrangement of th e expanded PAA chains in terms of hydration and conformation compared to the one adopted after spreading an d before the first compression.110

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57 Figure 3-10. Topographic AFM images of Dend2 LB f ilms transferred at 2 (a), 4 (b), 4.5 (c and d), 5 (e and f), 5.5 (g and h), 6 (i and j), and 8 mN/m (k and l). Figure 3-11. Compression-expansio n hysteresis plot of Dend2 (target pressure = 5 mN/m, pH = 2.5).

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58 3.3 Conclusions In this work, the A/W interfacial behavior of two dendrimer-like block copolymers based on polystyrene and poly (tert -butylacrylate) (Dend1) or poly(acr ylic acid) (Dend2) and their LB film morphologies on hydrophilic mica substr ates were investigated. Dend1 formed thermodynamically stable Langmuir monolayers and self-assembled into circular surface micelles up to 24 mN/m with a very low aggregati on number (~ 3), likely re sulting from the high P t BA wt % and from the peculiar dendrime r-like architecture. At 24 mN/m, the P t BA segments desorbed and aggregated on top of the water su rface, and all the monolayers formed beyond this threshold were metastable and relaxed down to 24 mN/m. Poly(acrylic acid) is surface active only under acidic pH conditions below its pKa va lue (~ 5.5), and a preliminary study on a PAA homopolymer (PAA250K, Mn = 250,000 g/mol) showed that it is able to form stable monolayers up to ~ 3.5 mN/m before dissolving in the wate r subphase. Because of its small PS wt %, Dend2 similarly did not form stable Langmuir monolay ers under high pH conditions, and therefore its self-assembly at the A/W interf ace was investigated only under acidic conditions. The isotherm indicated the presence of a pseudoplateau at 5 mN/m characteristic of a phase transition that corresponds to a pancake-to-brush transition, w ith the progressive aqueous dissolution of the PAA segments underneath the anchoring PS co res. For pressures below the pseudoplateau, Dend2 molecules also aggregated into circular surface micelles with a very low aggregation number (~ 5). This study conf irmed that various parameters such as for instance polymer architecture, chain length/polarity, surface de nsity, or even subphase pH can all strongly influence the self-assembly of block copolymer s at the A/W interface. Therefore, while this work gave some hint of the interesting interfacial properties of these two novel PSb -P t BA and PSb -PAA dendrimer-like copolymers, additional i nvestigations with other samples with

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59 different numbers of arms and chain lengths are necessary for a better understanding of the influence of the dendrimer-like structure. 3.4 Experimental Methods 3.4.1 Materials The synthesis of the PSb -P t BA (Dend1, Mn = 240,000 g/mol, PDI = 1.26) and PSb -PAA (Dend2, Mn = 139,000 g/mol, PDI = 1.28) dendrimer-lik e copolymers was real ized according to a previously reported procedure.100 These block copolymers consist of an eight-arm PS core ( Mn = 10,000 g/mol, ~ 12 styrene units/arm) with a sixteen-arm P t BA ( Mn = 230,000 g/mol, ~ 112 tert -butylacrylate units/arm, PS wt % ~ 4 %) or PAA ( Mn = 129,000 g/mol, ~ 112 acrylic acid units/arm, PS wt % ~ 7%) corona. The PAA homopolymer (PAA250K, Mn ~ 250,000 g/mol) was purchased from Aldrich Chemical Co. and was used as received without further purification. 3.4.2 Langmuir Films Surface pressure measurements were acco mplished by use of a Teflon Langmuir trough system ( W = 160 mm, L = 650 mm, KSV Ltd., Finland) equi pped with two moving barriers and a Wilhelmy plate. The PSb -P t BA dendrimer-like copolymer sample (Dend1) was prepared by dissolving approximately 1 mg of poly mer in 1 mL of chloroform. The PSb -PAA dendrimerlike copolymer (Dend2) and the PAA homopolymer (PAA250K) samples were prepared by dissolving approximately 1 mg of polymer in 1 mL of a chloroform/ethanol mixture (1/2 in volume). Volumes ranging from 10 to 30 L were spread dropwise with a gastight Hamilton syringe on Millipore filtered water (subphase resistivity 18.2 M .cm) of the desired pH value, and the spreading solvents were allowed to ev aporate for 30 min. In all the experiments, subphase temperature and barrier sp eed were kept constant at 25 C and 5 mm/min, respectively.

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60 3.4.3 AFM Imaging The LB films were formed by transferri ng the Langmuir films of Dend1, Dend2, and PAA250K onto freshly cleaved mica at various surface pressures. The desired surface pressure was attained at compression/expansion rates of +/-5 mm/min. Once the films had equilibrated at a constant surface pressure for 15 min, the mica substrate was then pulled out of the water at a rate of 1 mm/min. All the transfer ratios were close to unity unless otherwise stated, which is indicative of successful transfer. The transferred films were air-dri ed in a desiccator for 24 h and subsequently scanned in tapping mode with a Nanoscope III AFM (Digital Instruments, Inc., Santa Barbara, CA) using Nanosen sors silicon probes (dimensions: T = 3.8-4.5 m, W = 26-27 m, L = 128 m). All the images were processed w ith a second-order flattening routine.

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61 CHAPTER 4 LANGMUIR AND LANGMUIRBLODGETT FILMS OF POLY(ETHYLENE OXIDE)b POLY(-CAPROLACTONE) STAR-SHAPED AND LINEAR BLOCK COPOLYMERS 4.1 Introduction Poly(-caprolactone) (PCL) and poly(ethylen e oxide) (PEO) are two biocompatible polymers with PCL biodegradatio n leading to nontoxic products.111,112 Low molecular weight PEO is not biodegradable but can be eliminated from the body by the renal system.113 The introduction of a hydrophilic and highly flexible PE O block at the end of a PCL block allows the potential to tailor PCL properties such as its high hydrophobicity, high crystallinity, and slow biodegradation.114 Therefore, synthesis of PEOb -PCL copolymers with various architectures has resulted in a growing number of reports c iting potential applications including drug delivery systems, temporary bioabsorbable implants, and tissue engineering.112,115,116 The air/water (A/W) interface has received much attention to investig ate the self-assembly of various amphiphilic molecules because of its ability to mimic hydrophilic/hydrophobic interfaces. When polymers having biological applica tions are considered, such as PEO and PCL, the A/W interface is of particular interest becau se of its presence in many biological systems. Both PEO and PCL homopolymers spontaneously ad sorb at the A/W interface to form stable monolayers in a moderate surface pressure ra nge. PEO homopolymers have been extensively studied in solutions and at inte rfaces, and it has been shown that PEO chains irreversibly dissolve in the water subphase at relatively low surface pressures.117 Surprisingly, very little interest has been put into fundamentally understanding the aggregation in Langmuir monolayers of PCLbased block copolymers and PCL homopolymers. Leiv a et al. were to our knowledge the first to report on the A/W interfacial properties of PCL homopolymers, and they observed collapse pressure values ranging from 13 to 20 mN /m depending on the molecular weight, and aggregation of the hydrophobic PCL chains on top of the water surface after collapse.118 It is only

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62 very recently that Esker and co-workers extens ively studied PCL crystallization mechanism in the collapse region by Brewster angle micros copy and isobaric area relaxation analyses.101,119 The only example in the previous literature in vestigating the A/W self-assembly of PCL-based block copolymers was reported by Lee et al. for an architectur e with two linear PCL chains anchored to a dendri tic hydrophilic head.120 Chemically attaching a hydrophilic PEO bloc k to a hydrophobic PCL block enhances the amphiphilicity and the surface activity of the re sulting block copolymer, allowing higher surface pressures to be reached, as previously shown for other PEO-based amphiphilic block copolymers.22,23 To our knowledge, no work has been reported on the A/W interfacial behavior of block copolymers based on PEO and PCL. W ith a view toward guest encapsulation, we recently reported the synthesis of a series of poly(ethylene oxide)block -poly(-caprolactone) copolymers with star-shaped and linear architectur es by ring-opening polymerization of caprolactone at the end of hydroxyl-terminated star-shaped or linear PEO macroinitiators.121 In the present chapter, we study the behavior of these samples as well as the corresponding PEO and PCL homopolymers at the A/W interface (Langmuir monolayers) by surface pressure measurements (isotherms, compression-expans ion hysteresis, and isobaric relaxation experiments), and we employ AFM to charact erize the Langmuir-Blodgett (LB) filmsÂ’ morphologies after transfer onto hydrophilic mica substrates. The PEOb -PCL five-arm stars consist of a hydrophilic PEO core with 9 ethylene oxide units/ arm with hydrophobic PCL chains at the star periphery. Each st ar contains different amounts of PCL, varying from 0 to 18 caprolactone units/arm (Figure 4-1 and Table 4-1). The linear PEOb -PCL diblock copolymers synthesized from a linear PEO macroinitiator (PEO2670, Mn = 2,670 g/mol, ~ 60 ethylene oxide repeat units) contain diff erent amounts of PCL, varying from 11 to 35 -caprolactone repeat units

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63 (Figure 4-2 and Tabl e 4-2). The other PEO homopolymer PEO2000 ( Mn = 2,000 g/mol; PDI = 1.20) and the PCL homopolymers PCL1250 ( Mn = 1,250 g/mol; PDI = 1.50), PCL2000 ( Mn = 2,000 g/mol; PDI = 1.45), and PCL10000 ( Mn = 10,000 g/mol; PDI = 1.40) were commercially available (purchased from Aldric h Chemical Co.) and were used as received without further purification. Figure 4-1. The star-shaped PEOb -PCL block copolymers. Table 4-1. Characteristic values of the star-shaped polymers. Name PEO core Star#1 Star#2 Star#3 Star#4 Star#5 Star#6 Mn a (g/mol) 2,1504,2006,3708,2009,630 11,220 13,110 PDIb 1.101.251.371.351.45 1.36 1.44 Avg no. of ethylene oxide units per arm 99999 9 9 Avg no. of -caprolactone units per arm 036912 15 18 a Determined by 1H NMR b Determined by GPC calibrated with linear polystyrene standards.

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64 Figure 4-2. The linear PEOb -PCL block copolymers. Table 4-2. Characteristic values of the linear PEO macroinitiator and of the linear diblock copolymers. Name PEO2670 PEO60b PCL11 PEO60b PCL19 PEO60b PCL27 PEO60b PCL35 Mn a (g/mol) 2,6703,9404,7805,780 6,680 PDIa 1.051.101.131.11 1.24 Avg no. of ethylene oxide units 60606060 60 Avg no. of caprolactone units 0111927 35 a Determined by GPC calibrated with linear poly(ethylene oxide) standards. 4.2 Results and Discussion 4.2.1 PEO Homopolymers The isotherms of the five-arm PEO core for subphase pH values of 5.5 (Millipore filtered water) and 13 (0.1 M NaOH) are presented in Figure 4-3. The isothe rms of the linear PEO homopolymers (PEO2000 and PEO2670) are also incl uded. The inset shows the same isotherms normalized with respect to the number of ethylene oxide repeat units. For PEO2000 and PEO2670, the surface pressure increases until a pseudoplateau that corresponds to the irreversible aqueous dissolution of the PEO chai ns is reached at 5 and 6.2 mN/m, respectively. As previously described, Langmuir films of PEO homopolymers are thermodynamically stable for low surface pressures.117 Upon compression the monolayers collapse, and the water-soluble PEO chains irreversibly dissolve in the water subphase for pr essures that are molecular weight dependent (maximum collapse pr essure value ~ 10 mN/m for high molecular weight PEO).122

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65 The behavior of the PEO core significantly differs from that of the linear analogue PEO2000. No pseudoplateau is observed, and the pressure s lightly increases only for high compression, as indicated by the shift toward the low area per monomer region compared to PEO2000. The Millipore water pH (5.5) is acid ic enough to protonate the triamine present in the center of the PEO core, therefore increasing its water solubility compared to the neutral form. To investigate the pH influence on the su rface activity of the PEO core, a cont rol isotherm was carried out with a subphase pH value of 13, where the triamine is no longer protonated. The isotherm shape was very similar to that at pH = 5.5. A slightly increased pressure was obt ained for high compression, but no pseudoplateau was observed. The absence of a pseudoplateau and the small pressure increase only for high compression indicate a negligible surface activity of the adsorbed molecules and the presence of a nonstable film. This assumpti on was verified by carrying out compression-expansion hysteresis experiments on the PEO core for a target pressure of 2 mN/m (Figure 4-4). Successive compression/expansion cu rves shifted toward smaller mean molecular areas, which is indicative of a lo ss of material in the aqueous subphase. The pressure increase is thought to arise from a kinetic effect, where th e barrier compression speed is faster than the dissolution rate of the PEO core molecules into the aqueous subphase, l eading to a metastable monolayer. Compared to the linear analogue, th e star-shaped PEO core not anchored to hydrophobic chains has little or no surface activ ity at the A/W interface and is therefore thermodynamically more stable being solvated in the aqueous subphase than being adsorbed at the interface, independent of the surface pressure This behavior can be related to the high polarity (presence of five hydr oxyl groups) and the compact arch itecture (star-shaped) of the PEO core, which is therefore more likely to dissolve in the water subphase than the linear analogue.

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66 Figure 4-3. Isotherms of the PEO homopolymer s. (Inset) Same isotherms normalized with respect to the number of ethylene oxide units. Figure 4-4. Compression-expansion hysteresis plot of the PEO core (target pressure = 2 mN/m).

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67 LB films of the PEO core could not be pr epared because of its Langmuir monolayer instability, so only PEO2000 and PEO2670 were transferred at 2 mN/m. PEO crystallization from the bulk and organic solvents has been exte nsively investigated under various experimental conditions including in thin films.123,124 The AFM scan of the PEO LB films indicated the presence of a flat surface with no PEO crystals. PEO is highly hydrophilic, and previous studies showed that every ethylene oxide unit can be hydrated with up to three water molecules.125 Recent studies in PEOb -PCL systems indicated that hydrated PEO chains essent ially lost their ability to crystallize.126 The fact that we did not observe any crystallization in PEO2000 and PEO2670 LB films probably arose from a similar situation where as the films dried, the PEO chains remained highly hydrated and could not crys tallize. PEO also has a high affinity for the hydrophilic mica substrate, which can be another energy barrier preventing aggregation and chain folding necessary for crysta llization to take place. 4.2.2 PCL Homopolymers While the main objective of our study was to gain a deeper understanding of the A/W interfacial behavior of PEOand PCL-based block copolymers, a preliminary study on PCL homopolymers involving isotherm al and compression/expansion hysteresis experiments with experimental parameters (barrier speeds and targ et pressures) similar to the ones used for the linear and star-shaped PEOb -PCL samples needed to be done. The isotherms of the PCL homopolymers introduced earlier are presented in Figure 4-5, with a log scale on the x -axis for convenient visualization. The in set shows the same isotherms nor malized with respect to the number of -caprolactone repeat units. At low pressure s, the PCL chains are adsorbed at the interface with a behavior charact eristic of liquid expanded and liquid condensed phases. Below the collapse pressure, theoretical investigations by Ivanova et al. showed that PCL chain packing

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68 and orientation is probably surface pressure-dependent.127 The inset shows that below the collapse pressure, chain packing is not mol ecular weight-dependent. Compression-expansion hysteresis cycles were performed in this surface pressure range and all the compressionexpansion curves closely overlapped, conf irming the thermodynamic stability of the monolayers.128,129 Figure 4-5. Isotherms of the PCL homopolymers. (Inset) Same isotherms normalized with respect to the number of -caprolactone units. The collapse region of most amphiphilic mo lecules is more difficult to quantitatively analyze because it is a thermodynamically uns table pressure region where various phenomena such as desorption of molecules from the interface or local formation of multilayers can happen. Many polymers show viscoelastic be havior in this region, leading to surface properties that are barrier speed-dependent.130 As shown in Table 4-3, the collaps e pressure (defined as the point where a sudden change in slope is observed) is molecular weight-depe ndent, with the longer PCL chains collapsing at lower pressures. PCL is a highly hydrophobic polymer, and its collapse

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69 therefore results in the aggregation of the wa ter-insoluble PCL chains on top of the aqueous subphase. An interesting featur e characteristic of PCL colla pse is the obvious decrease in pressure after the collapse point a phenomenon that was attribut ed by Esker and co-workers to PCL crystallization directly on the water su rface. Longer PCL chains have increased hydrophobicity and crystallinity co mpared to smaller PCL chains, which explains the lower collapse pressure and increased pres sure drop after the collapse point. Table 4-3. Collapse pressure va lues of the PCL homopolymers. Name PCL1250 PCL2000 PCL10000 Collapse pressure (mN/m) for compression speed = 5 mm/min 14.612.9 11.1 Collapse pressure (mN/m) for compression speed = 100 mm/min N/A14.1 11.4 Further evidence for PCL crystallization came from the isotherms recorded for a barrier compression speed of 100 mm/min (Figure 4-6). The pressure decrease after the collapse point almost completely vanishes, and as shown in Ta ble 4-3 the collapse pressure increases. This indicates that in this case the rate of crystall ization is slow compared to the compression speed and that the resulting monolayers are metastable in this pressure region. Thermodynamic collapse pressure values could not be easily obtai ned experimentally with our equipment because it would require infinitely slow compressions. The collapse pressure for PCL1250 (100 mm/min) could not be accurately determined because its isotherm does not show a clear collapse, but the shallower turning point between 12 and 15 mN/m can nevertheless be attributed to the collapse “point” of this film.

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70 Figure 4-6. Isotherms of the PCL homopolym ers (compression speed = 100 mm/min). Compression-expansion hysteresis cycles were also carried out beyond the collapse point. Figure 4-7 shows the compression-expansion hyst eresis experiment ca rried out for PCL1250. The first compression is similar to the isotherm re ported in Figure 4-5. As the film is expanded, the pressure suddenly drops until an expansion pseudoplat eau appears at a pr essure significantly lower than the collapse pressure during compre ssion. This expansion pseudoplateau corresponds to the readsorption/melting of the PCL chains that had previously crystallized. This pseudoplateau pressure is molecu lar weight-dependent, with the smaller PCL chains readsorbing at higher pressure (10, 8, and 4 mN/m fo r PCL1250, PCL2000, and PCL10000, respectively). The compression curve of the second cycle is s lightly shifted toward smaller areas, and a decrease is observed fo r the collapse pressure. This phenom enon is the result of residual PCL crystals that remained on the water surface from the initial m onolayer compression and that act as nucleation sites for the crystalliza tion of the other adsorbed PCL chains.101,119 Further

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71 compression-expansion cycles essentially ove rlapped the second cycle with no noticeable pressure changes concerning the coll apse or the expansion pseudoplateau. Figure 4-7. Compression-expansio n hysteresis plot of PCL1250. Typical AFM images of the PCL ho mopolymers LB films transferred below monolayer collapse ( = 7 mN/m), before crystallization on th e water surface takes place, are shown in Figure 4-8a and 4-8d. Surprisingly, PCL crystals could be observed. According to the isotherms that are characteristic of liquid condensed phase s in this low surface pressure range, the PCL homopolymers are transf erred into smooth and hydrated m onolayers adsorbed onto the mica surface. We believe that upon drying, during and afte r transfer, part of the PCL chains leave the surface and crystallize, which likely results in a mica surface only partially covered with adsorbed or crystallized PCL chains. For comparison, PCL homopolymers were also transferred beyond monolayer collapse, after crystallization on the water su rface takes place (Figure 4-8b, 48c, and 4-8e). The transfer ratios were in this ca se significantly greater th an 1 (~ 2-3), which was predictable since crystallizati on and therefore intrinsic MMA decrease take place over time in

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72 this surface pressure range. PCL crystals were also observable, with spherulitic architectures significantly different from those obtained by Esker and co-workers directly at the A/W interface using BAM.101,119 This suggests that the AF M images recorded above mo nolayer collapse are not only the result of PCL crystallization at the A/W interface but also the result of additional PCL crystallization taking place during a nd after transfer. By use of cross-section analysis (Figure 48f), all the PCL crystals were determined to be approximately 7.5 nm thick, which is consistent with the previously reported liter ature on PCL lamellae thickness.131 The thickness was independent of PCL molecular weig ht, which indicates that the ch ains stretch perpendicular to the surface and fold every 7.5 nm with the crystals probably grow ing parallel to the surface. Nevertheless, further comparison between PCL crys tallization in LB films and the previously reported work on PCL crystallization in bulk,132 from an organic solution,133 or even in thin films134-136 remains difficult to make because diff erent types of variables are involved. Figure 4-8. Topographic AFM imag es of PCL homopolymers LB films transferred below and above monolayer collapse: PCL2000 at 7 (a) and 13 mN/m (b and c), and PCL10000 at 7 (d) and 11.2 mN/m (e). (f) Cross-sec tion analysis performed at the edge of a PCL2000 crystal.

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73 4.2.3 Star-Shaped PEOb -PCL Block Copolymers The isotherms of the PEOb -PCL five-arm stars are presente d in Figure 4-9. They exhibit essentially three different regions that can be attr ibuted to different conformations of the polymer chains. In the high MMA region, the surface pressu re slowly increases as the films are compressed until a pseudoplateau is reached for intermediate mean molecular areas. As the compression continues in the low MMA region, the surface pressure sharply increases, reaching elevated surface pressure values and highly compressed films. Figure 4-9. Isotherms of the star-shaped PEOb -PCL copolymers. 4.2.3.1 High MMA region The first step toward understanding the behavior of the stars in this region was to check monolayer formation reversibil ity and stability. This was done by carrying out compressionexpansion hysteresis experiments with target pressures up to 9 mN /m. For Star#6, Star#5, Star#4, and Star#3, all the compression and expansion cu rves are superimposable independent of the target pressure, which is indica tive of film formation reproducib ility and stability. These four stars have the largest PCL amounts and are therefore hydrophobic eno ugh so the amount of

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74 material adsorbed at the interf ace remains constant over time, wit hout irreversible dissolution in the aqueous subphase (Figure 4-10). As the PCL content is decreased, monolayer stability is reduced. For Star#2, the compression-expansion cycles start shifting toward smaller mean molecular areas, and this shift is even more pronounced for Star #1 (Figure 4-11). For these two samples, the small PCL chains are insufficient to overcome the overall st ar hydrophilicity arising from the water-soluble PEO core, and irreversible water dissolution takes place over time. Figure 4-10. Compression-expansio n hysteresis plot of Star#6 (target pressure = 9 mN/m). Figure 4-11. Compression-expansio n hysteresis plot of Star#1 (target pressure = 9 mN/m).

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75 From the initial study on the homopolymers, it was shown that in the low pressure region -caprolactone repeat units are adsorbed at the A/W interface independent of the molecular weight and that the PEO core alone has limited surface activity which leads to its irreversible dissolution in the aqueous subphase. For the st ar-shaped block copolymers, the interfacial behavior of the PEO core might be significantly changed as it is chemically attached to hydrophobic PCL chains. To estimate the interfacial area occupied by the PEO core of the starshaped block copolymers, only the isotherms of St ar#6, Star#5, Star#4, and Star#3 were used, as the corresponding Langmuir monolayers are therm odynamically stable below the pseudoplateau. For target pressures ranging from 1 to 11 mN/m the MMA was plotted versus the number of caprolactone repeat units as shown in Figure 4-12 The resulting curves were analyzed by linear regression leading to R2 values greater than 0.99. The lin ear relationships indicate that the adsorption of the PCL blocks is not molecula r weight-dependent as it is for linear PCL homopolymers. More interestingly, the y -axis intercepts are signifi cantly different from zero, indicating the non-negligible inte rfacial area occupied by the PEO core anchored by the PCL chains. The surface pressure wa s then plotted versus the y -axis intercept values to give the extrapolated isotherm of the PEO core of the block copolymers (Figure 4-13). The experimental PEO2000 isotherm was also included for comparis on. Both curves have been normalized with respect to the number of ethylene oxi de units. For low surface pressures ( 4 mN/m), the experimental PEO2000 and the extrapolated PEO co re isotherms overlap reasonably, indicating a similar interfacial area occupied by an ethylene oxi de repeat unit of the PEO core compared to the linear PEO analogue. The two curves stop overlapping above 4 mN/m because PEO2000 is irreversibly dissolved in the aqueous subphase. It is also very interesting to notice in the isotherms of the block copolymers, for surface pr essures lower than 11 mN/m, the absence of

PAGE 76

76 pseudoplateaus or inflection point s characteristic of PEO aqueous dissolution. This absence is also shown in the compressibility plot K versus surface pressure (Figure 4-14), where no peak (local maximum) is observed below 11 mN/m (in compressibility plots ve rsus surface pressure, every phase transition in a Langmuir monolayer results in a local compressibility maximum). This suggests that the PEO core of the star-shape d block copolymers is probably not adsorbed at the interface but more likely already solvated in the water subphase in the vicinity of the interface. Figure 4-12. Plots of MMA versus number of -caprolactone repeat units for different surface pressures from the isotherms of St ar#3, Star#4, Star#5, and Star#6. Figure 4-13. Isotherms of the PEO core extrap olated and PEO2000 normalized with respect to the number of ethylene oxide units.

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77 Figure 4-14. Compressibility pl ots of the star-shaped PEOb -PCL block copolymers versus surface pressure. 4.2.3.2 Intermediate MMA region This region is characterized by a pseudoplatea u in the isotherms and by a maximum in the compressibility plot (Figure 4-14). This phase transition occurs between approximately 12 and 15 mN/m, a similar pressure range as for the collapse pressure of PCL homopolymers. The pseudoplateau length correlates with the PCL chain le ngth in the stars, and this phase transition is attributed to the PCL segments aggregating and crystallizing above the interface and the PEO core, which is consistent with the work repo rted by Lee et al. on PCL-based block copolymers with a dendritic hydrophilic head.120 Crystallization of the PCL segments was also characterized by carrying out isobaric experiments for Star#6 with target pressures be low and within the pseudoplateau pressure range (9, 11, and 13 mN/m). The results of MMA decr ease versus time are presented in Figure 4-15, and the y -axis has been normalized to facilitate comparison. No or very little MMA decrease takes place over time for pressures below th e pseudoplateau (9 and 11 mN/m), which is indicative of thermodynamically stable monolayer s. As the target pre ssure is increased (13

PAGE 78

78 mN/m), PCL quickly collapses and crystallizes as indicated by the sharp initial area decrease. The MMA levels off around 1000 2, a value that correlates well with the MMA value obtained at the end of the plat eau in the isotherm. Figure 4-15. Isobaric relaxation plots of Star#6 at 9, 11, and 13 mN/m. PCL crystallization in the pseudoplateau re gion was finally inve stigated by hysteresis experiments. The compression-expansion curves fo r Star#6 with a target pressure of 15 mN/m are shown in Figure 4-16. As the barriers expand, an expans ion pseudoplateau appears that corresponds to the readsorption (melting) of the PCL chains previously crystallized. Interestingly, the second and third compression cu rves overlap each other but do not overlap the initial compression, with a slight shift towa rd the low MMA region and a decrease in the compression pseudoplateau pressure Similarly as it was observed for PCL homopolymers, this confirms that crystallization takes place fo r Star#6 in the pseu doplateau region during compression. Star#5, Star#4, and Star#3 have a similar behavior with the expansion pseudoplateau vanishing as the PCL amount is decr eased. Because of even lower PCL content in Star#2 and Star#1, no expansion pseudoplateau was observed, a nd the subsequent compression-

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79 expansion isotherms shifted toward smaller m ean molecular areas because of irreversible polymer dissolution in the water subphase (Figure 4-17), similarly as for low surface pressures. Figure 4-16. Compression-expansio n hysteresis plot of Star#6 (target pressure = 15 mN/m). Figure 4-17. Compression-expansio n hysteresis plot of Star#1 (target pressure = 15 mN/m). 4.2.3.3 Low MMA region In the low MMA region, the surface pressure sharply increases up to values as high as 35 mN/m. Such high surface pressures can be reache d because of the increased amphiphilicity of the block copolymers compared to the homopolym ers, even if the collapse pressure of the individual PEO and PCL blocks is surpassed. The fact that the isotherms of Star#6, Star#5,

PAGE 80

80 Star#4, and Star#3 overlap in th is region suggests that all the PCL chains have collapsed and crystallized above the interface, and that the sharp pressure increase arises mainly from interactions between th e hydrated PEO cores. Therefore, PCL crystallization probably takes place for these four stars with the PEO core st ill hydrated in the water subphase, with the PCL chains stretching and crystallizi ng away from the interface. The isotherms of Star#2 and Star#1 shift toward smaller mean molecular areas beca use of the water solubility behavior mentioned before. A cartoon of the polymer chainsÂ’ conf ormations as the Langmuir monolayers are compressed is proposed in Figure 4-18. It should be mentioned th at the experime nts discussed here do not provide enough information to full y understand the aggregation of the star-shaped PEOb -PCL block copolymers. For instance, eventu al phase separation between the different blocks leading to the formation of various surface micelles could not be dire ctly determined from surface pressure measurements. Figure 4-18. Proposed conformations modeling the adsorption of th e star-shaped block copolymers at the A/W interface versus surface pressure.

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81 4.2.3.4 AFM imaging Typical AFM images of the star-shaped block copolymers LB films are presented in Figure 4-19 at pressures below ( = 10 mN/m) and above ( = 30 mN/m) the pseudoplateau. Similarly as for PCL homopolymers, crystalline domains ar e observed for all the stars independent of the surface pressure except for Star#1, which was una ble to crystallize and only aggregated into dewetted domains (~ 1-2 nm thick). Crystallization in PEOb -PCL systems has been extensively investigated in the previous literature, but the number of variables infl uencing crystallization rates and morphologies is too larg e to allow any kind of generalizat ion. For instance, Deng et al. reported that, in PEOb -PCL four-arm stars, PCL crystallinity for a constant PCL chain length decreased as the PEO chain length was increased.114 Gan et al. observed that hydrophilic and highly flexible PEO segments enhance the hydroph ilicity and reduce the degree of crystallinity of the polyester. The PEO block was also shown to provide nucleation sites for the crystallization of the PCL block.137 Crystallization of PEOb -PCL block copolymers in thin films resulted in various types of spherulitic growths with crystallization of both PEO and PCL blocks.138-140 Nevertheless, it was widely demonstrated th at PEO and PCL crystallize in well-defined separated areas after their phase separation.141 Therefore, as PEO crys tallization is obviously difficult in LB films, probably as a result of residual hydration, we can reasonably assume that the crystals obtained on mica substrates are th e result of PCL crystallization only. Section analysis indicates a constant crystal thicknes s around 7.5 nm, which is consistent with the lamellae thickness obtained for PCL homopolymers.

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82 Figure 4-19. Topographic AFM imag es of the star-shaped PEOb -PCL copolymers LB films transferred below and above the pseudoplateau: Star#1 at 10 (a) and 30 mN/m (b); Star#2 at 10 (c) and 30 mN/m (d); Star#3 at 10 (e) and 30 mN/m (f); Star#4 at 10 (g) and 30 mN/m (h); Star#5 at 10 (i) and 30 mN/m (j); Star#6 at 10 (k) and 30 mN/m (l). From the previously reported literature, the PCL crystal unit cell has a length of 1.7297 nm that corresponds to two -caprolactone repeat units.142 PCL crystal thickness after transfer is around 7.5 nm for all the star-shaped block copolymer s, and if it is assumed that the PCL chains orient perpendicularly to the mica substrate, this thickness indicates that the chains fold approximately every eight -caprolactone repeat units. This would also support why the stars with a number of -caprolactone repeat units per PCL ch ain greater or close to eight all crystallized (Star#6, Star#5, St ar#4, Star#3, and Star#2), whereas Star#1, with only three repeat units per PCL chain, did not. Similarly as for PCL homopolymers, the star-s haped samples exhibited PCL crystals at low and high pressures, before and after crysta llization of the PCL bloc k at the A/W interface.

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83 Additional crystalli zation of the PCL segments therefore al so took place during and after transfer for the star-shaped block copolymers, which likel y leads to a mica surface only partially covered with adsorbed or crystallized polymer chains. At high surface pressures, dendritic and needlelike crystals could be seen. These crystal structures are significantly different from those observed for PCL homopolymers, which indicates that even though the PEO core did not crystallize, it strongly influenced the crystall ization of the PCL blocks in terms of crystal morphology. Many variables have to be taken in to consideration, such as mo lecular weight, PEO amount, film thickness, water evaporation, resi dual water content, transfer pre ssure, and substrate affinity for the polymer chains to fully investigate crysta llization of PCL homopolymers and PCL-based block copolymers in LB films. While this study gi ves some hint of the su rface properties of these interesting star-shaped block copolymers, comp lete understanding of the system will therefore require further investigation. 4.2.4 PEOb -PCL Linear Diblock Copolymers The PEO segment of the linear diblock copolymers (PEO2670, Mn = 2,670 g/mol) has a molecular weight in the same range as the one of the PEO core of the star-shaped PEOb -PCL samples. Nevertheless, because of its linear arch itecture, this PEO segment has intrinsic surface activity as shown in Figu re 4-3, which should lead to the ap pearance of PEO phase transitions not observable for the star-shaped samples in the low surface pressure region. The isotherms of the four linear PEOb -PCL diblock copolymers are presented in Figure 4-20. Compared to the homopolymers PEO2670 and PCL2000 (PCL homopolymer with a molecular weight in the same range as the PCL blocks of the linear diblock copo lymers), higher surface pr essures as high as 25 mN/m can be reached, similarly as for the star-shaped samples. As better shown in the compressibility plot (Figure 421), three phase tran sitions that corres pond to conformational rearrangements of the polymer chains are clear ly observed around 6.5, 10.5, and 13.5 mN/m. The

PAGE 84

84 local maxima in monolayer compressibility for th e two low pressure transitions increase as the PCL chain length decreases, suggesting PEO-related phase transitions as previously observed for comb-like polymers consisting of a poly(vinyl amine) backbone with 2kDa PEO side chains.143 The maximum in monolayer compressibility for th e high pressure transiti on increases as the PCL chain length increases, suggesting a PCL-rela ted phase transition. Comparison with the isotherms of PEO2670 and PCL2000 indicates that the transitions around 6.5 and 13.5 mN/m arise from dissolution of the PEO block in the water subphase and crysta llization of the PCL block above the water surface, respectively. Th e transition at 10.5 mN/m was not observed for PEO2670, but has been previously described as a brush formation of the PEO chains stretching away from the interface when anchored by hydr ophobic blocks for other PEO-based amphiphilic block copolymers.144,145 In the following, we report our inve stigations on the behavior of the linear PEOb -PCL diblock copolymers in the low ( < 12 mN/m) and high ( > 12 mN/m) surface pressure regions. Figure 4-20. Isotherms of the PEOb -PCL linear diblock copolymers.

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85 Figure 4-21. Compressibility plots of the PEOb -PCL linear diblock copolymers versus surface pressure. 4.2.4.1 Low surface pressure region ( < 12 mN/m) For surface pressures lower than the PEO aqueous dissolution around 6.5 mN/m, both the PEO and the PCL blocks are adsorbed at the A/W interface in a pancake conformation. To investigate the 2-dimensional miscibility of th e two blocks in more details, we prepared Langmuir monolayers with binary mixtures146-149 of PEO2670 and PCL2000, and the resulting isotherms are presented in Figure 4-22. Contra ry to the isotherms of the linear diblock copolymers, only 2 phase transitions corres ponding to PEO2670 aqueous dissolution (around 6.5 mN/m) and PCL2000 crystallizatio n (around 13 mN/m) are observed. The absence of a phase transition at 10.5 mN/m comes from the fact that PEO 2670, which is not chemically anchored by a hydrophobic PCL segment, is already irreversibly dissolved at this su rface pressure in the water subphase. This aqueous dissolution of PE O2670 (loss of material in the monolayer by solubilization in the subphase) can be observed more clearly in the hysteresis experiment in Figure 4-23 (49 mol % of PEO267 0), with a target surface pr essure of 9 mN/m, where the

PAGE 86

86 successive compression-expansion curves shift toward the low MMA region only below 6.5 mN/m. Above 6.5 mN/m, the curves overlap b ecause the amount of PC L2000 adsorbed at the A/W interface stays constant, independent of th e number of compression-expansion hysteresis cycles. Figure 4-22. Isotherms of PEO2670 and PCL2000 binary mixtures. (In set) Corresponding compressibility plots versus surface pressure. Figure 4-23. Compression-expansion hysteresis plot of the binary mixture with 49 mol % in PEO2670 (target pressure = 9 mN/m). It is also interesting to notice that the collapse surface pressure of PEO2670 slightly increases (up to 6.7 mN/m for 86 mol % of PC L2000) when increasing the amount of PCL2000

PAGE 87

87 in the mixed monolayers, as shown by the shift of the compressibility maximum toward higher surface pressures (inset of Figure 4-22). This is a firs t indication that PEO2670 and PCL2000 are miscible when both blocks are adsorbed at the A/W interface.150 Figure 4-24 shows plots of MMA versus the mole fraction of PCL2000 for th ree surface pressures below 6.5 mN/m (2, 3, and 4 mN/m). The data exhibit negative devia tions from ideal mixing (dashed lines), which confirms that in the surface pressure range wh ere they are adsorbed at the A/W interface ( < 6.5 mN/m), PCL2000 and PEO2670 do not phase-separ ate and thermodynamically interpenetrate each other.151,152 From these results, we can reasonably extrapolate that the PEO and PCL segments of the linear diblock copolymers are miscible as well below 6.5 mN/m, and therefore that their A/W interfacial adsorp tion probably does not lead to the formation of surface micelles previously observed for other amphiphilic block copolymers.97,153,154 These results are in good agreement with a previous study that dem onstrated the miscibility of PEO and PCL homopolymers in the amorphous phase in blend films prepared by solution casting.155 Figure 4-24. MMA plots versus mole fraction of PCL2000. Dashed lines: theoretical ideal mixing.

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88 The reversibility of the two PEO phase tran sitions of the linear diblock copolymers was investigated by carrying out compression-expansion hysteresis experiments110,156 on the block copolymer sample with the smaller PCL segment (PEO60b -PCL11) for a target pressure of 18 mN/m. The resulting /MMA curves and the corresponding co mpressibility plots are shown in Figures 4-25 and 4-26, respectively. After the fi rst compression, the curves in Figure 4-25 shift to the low MMA region, which is indicative of so me irreversibility in the PEO phase transitions. As shown in the compressibility plots, the loca l maximum at 6.5 mN/m disappears after the first compression whereas the maximum at 10.5 mN/m is still present, independent of the number of compression-expansion cycles. At 6.5 mN/m, we believe the PEO ch ains dissolve irreversibly in the aqueous subphase and adopt a mushroom c onformation. Nevertheless, because of the anchoring effect of the PCL segments, the PEO chai ns stay in the vicinity of the interface. Upon further monolayer compression, the PEO chains are compressed against each other and stretch perpendicularly to the interface to form a compact brush at 10.5 mN/m.22,23,144,157-160 During monolayer expansion, the PEO brus h reversibly relaxes, but the PEO chains do not readsorb and stay hydrated underneath the inte rface, which explains the complete absence of phase transition at 6.5 mN/m after the first compression. The maximum in compressibility corresponding to the transition at 10.5 mN/m is nevertheless slightly decreased after the fi rst compression, which suggests that the PEO chains do not completely re lax during the subsequent expansions to their original mushroom conformation of the first compression. It should be noticed that, contrary to our linear PEOb -PCL diblock copolymers, only one a pparent PEO phase transition around 10 mN/m is usually observed in the isotherms of PEO-based bloc k copolymers with high molecular weight PEO blocks ( Mn 10,000 g/mol),22 probably because PEO aqueous dissolution and brush formation take place simultaneously.

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89 Figure 4-25. Compression-expans ion hysteresis plot of PEO60b -PCL11 (target pressure = 18 mN/m). Figure 4-26. Compressibility plots of Figure 4-25 (PEO60b -PCL11, target pressure = 18 mN/m). Top curve: first compression. Bottom curve: first expansion, s econd compression, and second expansion.

PAGE 90

90 4.2.4.2 High surface pressure region ( > 12mN/m) In this surface pressure region, similarly as for the PCL homopolymers and the star-shaped block copolymers, the phase transition observed in Figures 4-20 and 4-21 at 13.5 mN/m arises from collapse and crystallization of the PCL segments above the water surface. The compression-expansion hysteresis experiment carri ed out on the linear block copolymer sample with the longest PCL block (PEO60b -PCL35) for a target pressure of 16 mN/m gives more insight on the crystallization/melting behavior of the PCL segments. The /MMA curves and the corresponding compressibility pl ots are shown in Figures 4-27 and 4-28, respectively. During monolayer compression, the hydro phobic PCL segments collapse a nd crystallize on top of the water surface as shown by the inflection points in the /MMA curves and the local maxima in the compressibility plots at 12. 5 and 13.5 mN/m. Similarly as fo r the PCL homopolymers and for the star-shaped samples, the collapse/crystalli zation surface pressure in the first cycle is approximately 1 mN/m higher than in the subse quent compressions (13.5 versus 12.5 mN/m), and also, after the first compression, the subseque nt curves are slightly shifted toward the low mean molecular area region. After the first hystere sis cycle, the PCL crystals that did not melt (i.e. did not readsorb at the A/W interface) act as nucleation sites to cata lyze the crystallization of other PCL segments during the subsequent cycles therefore lowering the crystallization surface pressure and shifting the compression isotherms toward lower mean molecular areas. During monolayer expansion, melting of the PC L segments was characterized in the /MMA plots for the star-shaped samples and the PCL homopolymer s by an expansion pseudoplateau at a surface pressure lower than for the crystallization. As shown in Figures 4-27 and 4-28, no pseudoplateau or sharp local maximum in compressibility are observed during the first expansion, whereas for the subsequent cycles the PCL segments clearl y readsorb around 5 mN/m (sharp local maximum

PAGE 91

91 in the compressibility plot). The presence of a broad melting transition du ring the first monolayer expansion is a little bit surprising because this behavior was not previously observed for the starshaped samples and the PCL homopo lymers, but it is probably relate d to a particular shape, size, or polydispersity of the PCL crystals formed during the first monolayer compression. It should be noticed that the crystallization and melting surface pressures reported here for linear diblock copolymers (as well as for the star-shaped bl ock copolymers and the PCL homopolymers) are not thermodynamic values and were shown to be strongly barrier speed dependent. If one could compress and expand the monolayers infinitely slowly, the crystallization and the melting surface pressures would respectively decrease a nd increase, probably leveling off to a common value. Figure 4-27. Compression-expans ion hysteresis plot of PEO60b -PCL35 (target pressure = 16 mN/m).

PAGE 92

92 Figure 4-28. Compressibility plots of Figure 4-27 (PEO60b -PCL35, target pressure = 16 mN/m). a: PCL crystallization at 13.5 mN/m during the 1st compression. b: PCL crystallization at 12.5 mN/m during the 2nd and 3rd compressions. c: broad PCL melting transition during the 1st expansion. d: PCL melti ng transitions during the 2nd and 3rd expansions. Crystallization of the linear PEOb -PCL diblock copolymers in the LB monolayers was finally evidenced by AFM imaging after transfer onto mica substrates for surface pressures above 13.5 mN/m, after crystallization of the PC L segments on the water surface took place. As shown in Figure 4-29 for a surface pressure of 15 mN/m, all the samples show hairlike/needlelike crystal structures, with a constant crystal thickness around 7.5 nm as determined from cross-section analysis. This thickness is consistent with the value obtained for the PCL homopolymers and the star-shaped block copolymer samples. The PEO chains are adsorbed onto the mica substrate and the PCL segments stretc h perpendicularly to the interface, folding approximately every 8 -caprolactone repeat units. These resu lts confirm what we observed for the star-shaped PEOb -PCL samples, where the PEO block hi ghly influenced crystallization of the PCL segments in terms of crystal morphology. Nevertheless, it is crucial to emphasize here

PAGE 93

93 once again that this brief crystal structure anal ysis is done for the LB films only and is not rigorously valid for Langmuir m onolayers, because film drying during LB film formation can lead to further crystallizati on of the PCL segments. Evidence for crystallization of the PCL segments in the star-shaped and the linear block copolymer samples directly at the A/W interface came from the isotherms, the hysteresis, and th e isobaric experiments, but no clear conclusions can yet be drawn in terms of crystal structures in the Langmuir monolayers. BAM experiments are currently underway to investigate more d eeply the in-situ and real-time PCL crystal growth/melting directly on the water surface for the star-shaped and the linear PEOb -PCL block copolymers. Figure 4-29. Topographic AFM images of the linear PEOb -PCL diblock copolymers LB films transferred after crystal lization of the PCL segment at the A/W interface ( = 15 mN/m). (a): PEO60b -PCL11 (b): PEO60b -PCL19 (c): PEO60b -PCL27 (d) and (e): PEO60b -PCL35 (f): Cross-section analysis on PEO60b -PCL35

PAGE 94

94 A cartoon summarizing the polym er chains conformations as the Langmuir monolayers of the linear PEOb -PCL diblock copolymers are compressed is proposed in Figure 4-30. For surface pressure values lower than 6.5 mN/m, bo th the PEO and the PCL segments are adsorbed at the A/W interface in a pancak e conformation (1). As the surface pressure is increased, the PEO segments irreversibly dissolve in the aqueous subpha se and adopt a mushroom conformation around 6.5 mN/m (2), before fo rming a brush above 10.5 mN/m upon further compression (3). Finally, around 13.5 mN/m, th e PCL segments collapse and crystallize perpendicularly to the interface (4). Figure 4-30. Proposed conformations mode ling the adsorption of the linear PEOb -PCL diblock copolymers at the A/W interface versus surface pressure.

PAGE 95

95 4.3 Conclusions In this chapter, the A/W interfacial behavior of various PEObPCL block copolymers and their LB film morphologies on hyd rophilic mica substrates were investigated, and the results were compared to PEO and PCL homopolymers. The isotherms of the star-shaped block copolymers indicated the presence of a single pha se transition characterized by a pseudoplateau that corresponds to the collapse and crystallization of the PCL chains above the water surface. Below the plateau, the PCL segments are adsorbed, anchoring the water-soluble star-shaped PEO core in the vicinity of the interface. Compressi on-expansion hysteresis experiments showed that, in this region, the spread monolayers are ther modynamically stable except the ones containing the smallest PCL amounts, which irreversibly dissolved in the water subphase. In the pseudoplateau region, PCL homopolymers crystalli zed directly at the A/ W interface as well as the PCL segments of the star-shaped block copolymers. Above the pseudoplateau, the isotherms of the star-shaped block copolymers with the longe st PCL chains overlapped, indicating that all the PCL chains have collapsed and that the sharp pressure increase mainly arises from interactions between the hydrated PEO cores. Compression-expansion hysteresis experiments indicated that the readsorption/melting of the PCL segments takes place at a lower surface pressure than for the crystallization. AFM im aging of the homopolymers and the star-shaped block copolymers LB films was complicated by the fact that both PEO and PCL are highly crystalline polymers that can undergo morphol ogical changes during m onolayer transfer. The PEO homopolymers did not crystallize, probabl y because residual hydration or large hydrophilic substrate/PEO monolayer interact ions inhibited crystal formati on. The PCL homopolymers and the star-shaped block copolymers crystallized di rectly at the A/W interface only above the PCL collapse pressure, but additional crystallization could take place during water evaporation on the mica substrates. Various crystal morphologies were observed for the star-shaped block

PAGE 96

96 copolymers such as spherulitic, dendritic, and need lelike structures, with the presence of the PEO core strongly influencing the crystallization of the PCL blocks. The li near diblock copolymers successfully self-assembled as well at the A/W interface to form stable Langmuir monolayers. Preliminary investigation on PEO2670 and PCL 2000 homopolymers blends showed that these polymers are non-ideally miscible for low surface pr essures when both blocks are adsorbed at the A/W interface. Nevertheless, the individual collapse surface pressures (PEO2670 aqueous dissolution around 6.5 mN/m and PCL2000 crysta llization above the interface around 13 mN/m) were not significantly influen ced by the presence of the othe r homopolymer. For the linear PEOb -PCL diblock copolymers, an additional PEO phase transition at 10.5 mN/m was observed corresponding to the formation of a PEO brush underneath the anchoring PCL segments. These two PEO phase transitions were not observed for the star-shaped PEOb -PCL block copolymers, and our investigations conse quently confirmed the significant influence of the polymer architecture on its interfacial proper ties. AFM imaging of the linear PEOb -PCL diblock copolymers LB films for high surface pressures c onfirmed the formation of PCL crystals with hairlike/needlelike architectures. These crystals were significantly differe nt from those obtained in LB films of PCL homopolymers, confirming the strong influence of the PEO block on the crystallization of the PCL segments. This fundam ental investigation gave interesting insight on the interfacial self-assembly of PEOb -PCL copolymers and showed that an accurate and easy control of the conformations and the orientations of the different blocks at the A/W interface can be easily achieved by simply varying the polymer architecture or the surface pressure. 4.4 Experimental Methods 4.4.1 Langmuir Films Surface pressure measurements were acco mplished by use of a Teflon Langmuir trough system ( W = 160 mm, L = 650 mm; KSV Ltd., Finland) equi pped with two moving barriers and a

PAGE 97

97 Wilhelmy plate. Between runs, the trough was cleaned with ethanol and rinsed several times with Millipore filtered water (resistivity 18.2 M .cm). The samples were typically prepared by dissolving approximately 1 mg of polymer in 1 mL of chloroform. Volumes ranging from 10 to 30 L were spread dropwise on a Millipore filtered water subpha se with a gastight Hamilton syringe. The chloroform was allowed to evaporat e for 30 min to ensure no residual solvent remained. When not in use, the volumetric flasks containing the polymer solutions were wrapped with Teflon tape followed by Parafilm and stored at 10 C in order to prevent changes in concentration due to chloroform evaporation. In all the experiments, subphase temperature and barrier speed were kept constant at 25 C and 5 mm/min, respectively, unless otherwise stated. 4.4.2 AFM Imaging The LB films were formed by transf erring the Langmuir films of the PEOb -PCL block copolymers (linear and star-shaped) and the homopolymers onto freshly cleaved mica at the desired surface pressure which was attained at compression/expansion rates of +/-5 mm/min. Once the films had equilibrated at a constant surface pressure for 15 min, the mica substrate was then pulled out of the water subphase at a rate of 1 mm/min. All th e transfer ratios were close to unity unless otherwise stated, which is indicativ e of successful transfer. The transferred films were air-dried in a desiccator for 24 h and s ubsequently scanned in tapping mode with a Nanoscope III AFM (Digital Instruments, Inc., Santa Barbara, CA) by use of Nanosensors silicon probes (dimensions: T = 3.8-4.5 m, W = 26-27 m, L = 128 m). All the images were processed with a second-order flattening routine.

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98 CHAPTER 5 TWO-DIMENSIONAL POLYMERIC NANOM ATERIALS THROUGH CROSS-LINKING OF POLYBUTADIENEb -POLY(ETHYLENE OXIDE) MONOLAYERS AT THE AIR/WATER INTERFACE 5.1 Introduction The idea of stabilizing amphiphilic self-assem blies by polymerization was introduced at least thirty years a go for monolayers and about ten years later for bilayer vesicles.161,162 This approach to bridging the nanoscale world of labile, interfacially driven self-assemblies with the meso-scale has resulted in several exam ples of cross-linked 3D structures.163-167 For example, Bates and co-workers were the first to succeed in retaining the cylindrical morphology formed by gigantic wormlike rubber micelles of polybutadieneb -poly(ethylene oxide) (PBb -PEO) diblock copolymers in water by chemical cross-linking of the PB cores through their pendant 1,2-double bonds.163,167,168 However, relatively few groups have s hown interest in st abilization by crosslinking of two-dimensional (2D) polymeric self -assemblies formed at the air/water (A/W) interface; most studies have i nvolved interfacial polymerization of small molecules in Langmuir monolayers.169-198 In the early 1970’s, Ve yssi and co-workers180,190,191,193 were the first to demonstrate the formation of 2D cross-linked materials by cr oss-linking monolayers of dimethacrylates and several other difunctional reactive amphiphiles under UV irradiation for a constant surface pressure at the A/W or the oil/ water interface. This idea inspired other research groups and several examples followed. Regen and co-workers introduced the concept of a 2D-network of molecular pores, i.e. “perforate d monolayers” derived from calix[ n ]arene-based amphiphiles.183188 Cross-linking with malonic acid or via UV irradiation enabled them to synthesize porous and cohesive “perforated monolayers” with pore diam eters in the range 2-6 potentially applicable for gas permeation selectivity.186,187,189 Michl and co-workers sy nthesized grids through the

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99 coupling of star-shaped monomers for ced to adhere to a mercury surface.194,195 After polymerization, well-defined covalent 2D s quareor hexagonal-grid polymers could be synthesized,194,195,199 and analogous supramolecular r outes were also proposed.200-202 Palacin and co-workers reported on cross-linking porp hyrins through molecular recognition between oppositely charged monomers at the A/W interface.196-198 Kloeppner and Duran171 were the first to demonstrate the possibility to remove from th e water surface free-standing fibers of 2D crosslinked 1,22-bis(2-aminophenyl)docosane polyanilin es. Finally, alkylalkoxysilanes have been widely used,177-179,203,204 and our group has for instance inve stigated some of the fundamental aspects of the A/W interfacial cross-linki ng of octadecyltrimethoxysilane (OTMS) and octadecyltriethoxysilane (OTES) under acidic conditions.177-179,203 However, relatively few groups have shown interest in stabilizing by cros s-linking 2D “true” polymeric self-assemblies at the A/W interface. To our knowledge, only one example based on a lipopolymer was previously proposed by O’Brien and co-workers involvi ng network formation by photopolymerization.205 Our interest is to cross-link monolayers of block copolymers to achieve porosity at the submicrometer scale. In this chapter, the synthesi s of a 2D polymeric nano material consisting of a continuously cross-linked PB network containing PEO domains of controllable size is illustrated. This work was done in collaboration with Rachid Matmour, graduate student in the Duran group at the University of Florida. Such thin films ha ve potential applications in the preparation of membranes which will show large differences in permeability to water, methanol, and other polar compounds, depending on the PEO “pore” size. We report in this chapter the 2D self-conde nsation, at the A/W interface and under acidic conditions, of a trietho xysilane-functionalized PBb -PEO three-arm star block copolymer (PB core and PEO corona) and of a triethoxysilanefunctionalized linear PB homopolymer in a

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100 preliminary investigation. Using PB, which pe ndant double bonds have been hydrosilylated with trialkoxysilanes, as the cross-li nkable block is a novel approach that can be applicable to a variety of other polydiene-based block copolymers in order to retain a specific morphology at the nanoscopic scale. The surface properties of th e cross-linked monolayers were characterized by surface pressure measurements such as surface pressure ()-mean molecular area (MMA) isotherms at different reaction times, and isobari c experiments for various subphase pH values. The morphologies of the Langm uir monolayers were studied by atomic force microscopy (AFM) imaging of the corresponding La ngmuir-Blodgett (LB) films. 5.2 Results and Discussion 5.2.1 Hydrosilylated PB Homopolymer 5.2.1.1 Hydrosilylation reaction To demonstrate the viability of the 2D cro ss-linking method, we chose to first focus on a commercially available linear PB homopolymer ( Mn = 11,050 g/mol, ~ 204 butadiene repeat units). Many publications and patents can be found in the literature on the hydrosilylation of polymers.206-217 In most cases, the hydrosilylated polydienes were used as precursors to synthesize macromolecular complex architecture s such as arborescent graft polybutadienes,218 multigraft copolymers of PB and polystyrene,219 or side-loop polybutadienes.220 Triethoxysilane was used here as the pendant double bond hydrosily lating agent in stoichiometric amount with the total molar amount of repeat units in the PB homopolymer and in the presence of Karstedt catalyst (platinum catalyst) as shown in Figure 5-1. The reaction was carried out under argon for 24 h at 80 C in dry toluene (w ater free environment). After wo rkup, the hydrosilylated PB was analyzed by 1H NMR and FTIR spectroscopies (F igures 5-2, 5-3, and 5-4).

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101 Figure 5-1. Hydrosilylation of the penda nt double bonds of the PB homopolymer. Figure 5-2. 1H NMR spectrum of the PB homopolymer.

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102 Figure 5-3. 1H NMR spectrum of the hydrosilylated PB homopolymer. Figure 5-4. FTIR spectra of the PB hom opolymer before and after hydrosilylation. The 1H NMR spectrum of the PB starting material was used to determine the distribution of 1,2and 1,4-units. The two protons of the pendant vinyl carbon in the 1,2-units (=C H2) and the other hydrogens in the double bonds (-C H =C H and –C H =CH2) having chemical shifts of 4.9 and 5.4 ppm, respectively, the PB homopolymer tu rned out to be composed of 89 mole % of 1,2-

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103 units (Figure 5-2). The 1H NMR spectrum of the hydrosilylated PB revealed a strong decrease in the intensity of the signal corresponding to the -CH=C H2 ( = 4.9 ppm) protons. Furthermore, the appearance of intense peaks at = 1.2 and 3.8 ppm corresponding respectively to the –Si– OCH2C H3 methyl protons and the –Si–OC H2CH3 methylene protons is indicative of a high degree of conversion. However, some pendant double bonds remained unreacted after hydrosilylation (Figure 5-3). Based on the integration va lues of the signals at = 4.9 and 5.4 ppm, a conversion of 75 % of the 1,2-PB pendant double bonds was found, assuming that triethoxysilane reacts predomin antly with the 1,2-PB units as previously demonstrated.221 This result was confirmed by FTIR spectroscopy as s hown in Figure 5-4, where the absorbance peaks at 3100 cm-1 (=CH2 anti-symmetric stretch) and 1640 cm-1 (alkenyl –HC=CH2 stretch) strongly decreased in intensity after hydrosilylation. 5.2.1.2 Cross-linking reaction at the A/W interface After characterization of the PB68co -PB(Si(OEt)3)136 triethoxysilane-functionalized PB, its A/W interfacial cross-linking by self-condensati on of the triethoxysilane groups was studied. This 2D acid-catalyzed condensation reaction invol ves two different steps as shown in Figure 55: hydrolysis of the ethoxy groups with elimin ation of ethanol, followed by condensation between the resulting silanols. Se veral isotherms were first record ed after different reaction times (subphase pH = 3.0) as shown in Figure 5-6 with a fast barrier compression speed (100 mm/min) to prevent additional cross-li nking during monolayer compressi on. As the reaction time is increased, the isotherms shift toward the low mean molecular area region because of the irreversible loss of ethanol a nd water molecules into the wate r subphase during the hydrolysis and condensation steps, respectively. As shown in Figure 5-7, the monol ayer’s static elastic modulus s (calculated from Equation 3-1101) significantly increases versus reaction time,

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104 indicating that the material becomes more and more rigid as the exte nt of cross-linking is increased. For reaction times longer than 10 h, the isotherms essentially overlapped which indicates completion of the cross-linking. Figure 5-5. Cross-linking react ion involving hydrolysis and conde nsation of the triethoxysilane groups. Figure 5-6. Surface pressure-Mean Molecular Area isotherms of the hydrosilylated PB carried out after different reaction times (subphase pH = 3.0).

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105 Figure 5-7. Static elasti c modulus-surface pressure curves of the hydrosilylated PB homopolymer at different reaction times (subphase pH = 3.0). From the isotherms, the interfacial area occupied by one silane repeat unit before reaction and its decrease during cross-linking were estimated ( = 5 mN/m, pH = 3.0) and compared with the values previously reported for OTES under similar experimental conditions. The MMA for the hydrosilylated PB decreases from 6300 2 (46 2/silane repeat uni t) down to 3520 2 (26 2/silane repeat unit), which corresponds to a decrease ( A ) of approximately 20 2/silane repeat unit. These values are in very good ag reement with the ones reported for OTES (46 2/molecule before cross-linking, 24 2/molecule after cross-linking, and A = 22 2/molecule) and clearly indicate that the ex tent of Sol-Gel cross-linking is not reduced when starting from true polymeric chains compared to single alkylalkoxysilane molecules. The pH influence on the cross-linking reacti on kinetics was shown by carrying out isobaric experiments at = 10 mN/m and for different subphase pH values as shown in Figure 5-8. As expected, the MMA decreases faster for lower pH values. The isobar at pH = 7.0 shows a very

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106 slow creep over time which demonstrates that th e reaction is likely insi gnificant under neutral pH conditions. For lower pH values (pH = 2.0 and 3. 0), the curves overlap with the MMA leveling off after about 7 h indicating completion of the cr oss-linking reaction. The cross-linking kinetics are consistent with those reported for OTES and are slower compared to the results obtained for OTMS,177-179,203 which is related to the slower elimina tion of larger alkoxy substituents during the hydrolysis step. Figure 5-8. MMA-time isobars of the hydrosilylated PB for va rious subphase pH values ( = 10 mN/m). Upon completion of the cross-linking reacti on, the cross-linked material could be subsequently manually removed from the interface with a spatula after its compression to a final area of ca. 2 x 15 cm2 (Figure 5-9), leading to a film appr oximately 50 monolayers thick. It was self-supporting and gel-like, and could be collected as elongated sheets, which in turn could be drawn into very long fibers at high elongation. As e xpected, it was insolu ble in common organic solvents such as chloroform or THF, making molecular weight analysis by SEC impossible.

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107 Figure 5-9. (A and B) Removal of the cross-linked hydrosilylated PB from the water surface. (C) The long cross-linked vacuum-dried fiber. 5.2.1.3 AFM imaging The evolution of the monolayer morphology during cross-linking was characterized by AFM imaging of the LB films transferre d onto mica substrates (Figure 5-10, = 10 mN/m). As a control experiment, it was firs t observed that under neutral pH conditions (pH = 7.0, no crosslinking), the hydrosilylated PB forms a smooth and featureless monolayer (Figure 5-10B), in opposition to the highly hydrophobic PB starting material which forms typical rubbery continuous aggregates above the water surface (F igure 5-10A). After its hydrosilylation, the PB becomes amphiphilic (hydrophobic backbone and hydr ophilic triethoxysilane side groups) and consequently surface active with the triethoxys ilane pendant groups solvated into the water subphase. This interfacial property of the hydros ilylated PB was also shown in the isotherms

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108 where stable monolayers could be formed for surface pressures as high as 40 mN/m before collapsing (Figure 5-6). Afte r 20 minutes of reaction ( 50 % extent of cross-linking according to the isobar at pH = 3.0 and = 10 mN/m), the cross-linked material becomes more hydrophobic and can be clearly observed in Fi gure 5-10C (bright area s) with an average height of 1 nm as determined by cross-section analysis (Figure 510E). The cross-linked PB has irregular borders and does not cover yet the entire mica surface. An AFM image obt ained after completion of the cross-linking reaction is shown in Figure 5-10D (10 h, pH = 3.0, = 10 mN/m). Under these experimental conditions, most of the mica surf ace was covered with a smooth and cross-linked monolayer. Therefore, we deliberately found an area with a crack (that probably formed during film transfer) to clearly show the presence of the cross-linked monolayer (bright area) on top of the mica substrate with a thickness that stays co nstant around 1 nm duri ng cross-linking (Figure 5-10F). The acid-catalyzed condensat ion between the triethoxys ilane pendant groups of a hydrosilylated PB obtained by hydr osilylation of a commercial PB homopolymer has been successfully applied in this preliminary investiga tion to the preparation of cross-linked polymeric monolayers without any reagents or additives directly at the A/W interface. This technique opens up the possibility to retain a sp ecific 2D morphology at the nanoscopic scal e as exemplified in the following part for PBb -PEO three-arm star block copolymers.

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109 Figure 5-10. AFM topographic images of the LB films transferred onto mica substrates at = 10 mN/m: the commercial PB homopolymer (A) and the corresponding hydrosilylated PB at pH = 7.0 (B; t = 0 h) and 3.0 for different reaction times (C ; t = 20 min and D; t = 10 h). (E and F) Cross-section analysis of the images C and D. The images are 7 x 7 m2 (A) and 50 x 50 m2 (B, C, and D). 5.2.2 Hydrosilylated PBb -PEO Three-Arm Stars The surface properties of a new set of (PBb -PEO)n (n = 3 or 4) amphiphilic threeand four-arm star block copolymers at the A/W in terface were recently investigated in our group.222 A divergent anionic polymerization method yiel ded star-shaped block copolymers with well-

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110 defined architectures, molecular weights, and block volume fractions. Different (PBb -PEO)3 amphiphilic three-arm star block copolymers exhi biting narrow molecular weight distributions were prepared with poly(ethyle ne oxide) coronas over a broad range of volume fractions as shown in Table 5-1. Isothermal characterizatio n of the three-arm stars at the A/W interface indicated the presence of three characteristi c regions: a “pancake” region (I) in the high MMA region where the surface pressure slowly incr eases as the monolayer is compressed; a pseudoplateau around 10 mN/m (II) that corresponds to the aqueous dissolution of the PEO chains; and finally a compact brush region (III) in the low MMA region where the sharp increase in surface pressure originates only from the interactions between the hydrophobic PB segments (Figure 5-11). The dotted lines in Figure 5-12 also show the extr apolations used to estimate the three corresponding parameters Apancake, Ao, and A A fit of the pseudoplateau data revealed a linear dependence of A with the number of EO units ( y = 12.351 x 0,4889; R2 = 0.99), indicating that the length of the pseudoplateau linearly increases as the amount of PEO in the star-shaped block copolymers is increased (Figure 5-13). Table 5-1. Number average molecular weights a nd polydispersity indexes of the three-arm star block copolymers. Run Mna (SEC) Mnb (1H NMR) Mn c (theo.) Mw/ Mn a) Code 1 45900 42500405001.2(PB200b -PEO76)3 2 56000 75500775001.15(PB200b -PEO326)3 3 58000 1605001645001.2(PB200b -PEO970)3 4 74000 3205003230001.2(PB200b -PEO2182)3 5 135500--(PB(Si(OEt)3)b -PEO)3 a Apparent molecular weights determined by SE C in THF using a polystyrene calibration. b Estimated by 1H NMR analysis. c Mn,th = MButadiene x ([Butadiene]/[-PhLi]) x 3 + MEO x ([EO]/[(PB-OH)3].

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111 Figure 5-11. Surface Pressure-MMA isotherms for the (PB200b -PEOn)3 three-arm star block copolymers (n = 76, 326, 970, and 2182). Figure 5-12. Isotherm of (PB76b -PEO444)4 depicting how Apancake, Ao, and Apseudoplateau are determined.

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112 Figure 5-13. Linear dependence of Apseudoplateau on the total number of ethylene oxide units. 5.2.2.1 Hydrosilylation reaction Similarly as for the PB homopolymer, the hydr osilylation reaction was applied here to the PB segments of the (PB200b -PEO326)3 three-arm star block copolym er using triethoxysilane in stoichiometric amount with the total molar amount of double bonds in the PB block (1,2 and 1,4 units) as shown in Figure 5-14. After workup, th e hydrosilylated block copolymer was analyzed by 1H NMR and FTIR spectroscopies (Figures 5-15 and 5-16). Figure 5-15 shows the 1H NMR spectra of the (PBb -PEO)3 three-arm star block copolymer before and after hydrosilylation. The 1H NMR spectrum of the starting material was used to determine the distribution of 1,2and 1,4-units in the PB block, sim ilarly as previously

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113 discussed for the PB homopolymer. The PB block of the star-shaped block copolymer turned out to be composed, before hydrosilylation, of 75 mole % of 1,2-PB units. The 1H NMR spectrum of the hydrosilylated (PB(Si(OEt)3)b -PEO)3 three-arm star block copolymer revealed a strong decrease in the intensity of the signal corresponding to the -CH=C H2 protons of the pendant double bonds at = 4.9 ppm. Furthermore, the fact that the signal corresponding to the SiOCH2C H3 methyl protons at = 1.2 ppm greatly increased in intensity indicated that the reaction occurred with a high efficiency, and a conversion of 85 % of the 1,2-PB pendant double bonds was calculated. The efficien cy of the reaction was confir med by FTIR spectroscopy as shown in Figure 5-16, where the absorbance peaks at 3100 cm-1 and 1640 cm-1 strongly decreased in intensity after hydrosilylation. Figure 5-14. Hydrosilylation of th e pendant double bonds of the (PBb -PEO)3 three-arm star block copolymers.

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114 Figure 5-15. 1H NMR spectra of the (PB200b -PEO326)3 star block copolymer and the corresponding hydrosily lated (PB(Si(OEt)3)b -PEO)3 star block copolymer. Figure 5-16. FTIR spectra of the (PB200b -PEO326)3 star block copolymer and the corresponding hydrosilylated (PB(Si(OEt)3)b -PEO)3 star block copolymer.

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115 5.2.2.2 Cross-linking reaction at the A/W interface The A/W interfacial behavior of the (PB(Si(OEt)3)b -PEO)3 three-arm star block copolymer was first studied thro ugh isotherm experiments for a subphase pH value of 3.0 (Figure 5-17). The (PB(Si(OEt)3)b -PEO)3 star was initially spread on the water surface, the cross-linking reaction (pH = 3.0) was carried ou t for 10 h in the liquid expanded region of the isotherm at zero pressure, and then the isotherm was recorded as shown in Figure 5-17 (bottom red curve). For comparison, the top blue curve illustrates the same sample spread and rapidly compressed (barrier compression speed = 100 mm /min) at pH = 3 before any significant triethoxysilane hydrolysis or condensation occurs. The isotherm of the non-hydrosilylated star is also included (middle black curve). The (PB(Si(OEt)3)b -PEO)3 star block copolymer before cross-linking occupies a larger interfacial area compared to th e non-hydrosilylate d star because of the molecular weight increase during reaction and also because of the increased affinity for the A/W interface of the hydrosilylated PB block that spreads better than the highly hydrophobic non-hydrosilylated PB block. Concerning the isothe rm recorded after completion of the crosslinking reaction (bottom red curv e), a significant shift toward the low mean molecular area region was observed, similarly as for the hydrosily lated PB homopolymer, because of the loss of ethanol and water molecules. Another interestin g feature is that the pseudoplateau at 10 mN/m almost completely vanished for the unreacted hydrosilylated material, while it reappears upon cross-linking. This pseudoplateau corresponds to the desorption of the PEO chains from the interface into the aqueous subphase.223,224 Since the interfacial area occupied by the PB blocks after their hydrosily lation significantly increases, the fr actional area occupied by the PEO segments therefore significantl y decreases (even though the tota l area occupied by the PEO segments stays constant), which leads to a PEO phase transition (pseudoplateau) much less pronounced. As the cross-linking reaction proceeds the area occupied by the cross-linked PB

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116 segments decreases, which results in an increas e of the fractional area occupied by the PEO segments and, as a consequence, in a more pronounced pseudoplateau. Figure 5-17. Surface Pressure-MMA isotherms of the (PB200b -PEO326)3 star block copolymer and of the corresponding hydr osilylated (PB(Si(OEt)3)b -PEO)3 star block copolymer before and after cross-linking. Similarly as for the hydros ilylated PB homopolymer, seve ral isotherms were also recorded for the hydrosilylated (PB(Si(OEt)3)b -PEO)3 star block copolymer after different reaction times (pH = 3.0) as s hown in Figure 5-18A. Fresh monol ayers were spread for every isotherm and the barrier compression speed was set to 100 mm/min to pr event additional crosslinking during compression. As the reaction pro ceeds, the isotherms shift toward the low MMA region because of a more compact cross-linked material, with the PEO pseudoplateau becoming more and more pronounced because of the PEO fractional area influence mentioned above. The reappearance of the PEO pseudoplateau is better shown by plotting monol ayer compressibility versus MMA for different reaction times as shown in Figure 5-18B, where the maximum in

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117 compressibility, which is indicativ e of the PEO phase transition, significantly increases as the cross-linking proceeds. The monolayer compressibility ( K ) was calculated from Equation 3-2. Figure 5-18. Surface Pressure-MMA isotherms (A) and compressibility-MMA curves (B) of the hydrosilylated (PB(Si(OEt)3)b -PEO)3 star block copolymer at various reaction times (subphase pH = 3.0).

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118 The pH influence on the cr oss-linking reaction kinetics is shown by the isobaric experiments carried out at = 5 mN/m for different subphase pH values. This low surface pressure was chosen to avoid the region of the PEO-related phase transition (pseudoplateau), where the brush formation could lead to an addi tional decrease in MMA. As shown in Figure 519, the results are consistent with those obtai ned for the hydrosilylated PB homopolymer. As expected, the MMA decreases faster for lower pH values, and the MMA levels off after about 7 h for pH = 3.0. Figure 5-19. Isobars of th e hydrosilylated (PB(Si(OEt)3)b -PEO)3 star block copolymer for various subphase pH values ( = 5 mN/m). The cross-linked material could be here agai n removed from the interface with a spatula after its compression to a final area of ca. 2 x 15 cm2 (Figure 5-20), resulting in a film approximately 50 monolayers thick. This material had the same physical appearance as the crosslinked hydrosilylated PB homopolymer, it was inso luble in common organic solvents, self-

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119 supporting and gel-like unlik e the non-hydrosilylated (PBb -PEO)3 star block copolymer, and could also be collected as elonga ted elastic sheets draw n into very long fibers at high elongation. Figure 5-20. Removal of the cross-linked (PB(Si(OEt)3)b -PEO)3 three-arm star copolymer from the Langmuir trough surface. 5.2.2.3 AFM imaging The morphologies of the LB fi lms transferred onto mica substr ates after cross-linking at different surface pressures were characterized by AFM. (Figure 5-21). All the transfer ratios

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120 were close to unity, so it is assumed that the morphologies observed in Figure 5-21 are not modified during LB film formation. In a control experiment for a LB film prepared prior to any significant cross-linking takes place ( = 5 mN/m, pH = 7.0), a smooth and featureless monolayer with no phase separati on between the hydrosilylated PB blocks and the PEO blocks was obtained (Figure 5-21A). Afte r the hydrosilylation reaction, the PB blocks become more hydrophilic because of the triethoxysilane pendant groups and are therefore adsorbed at the A/W interface like the PEO blocks. This interfacial property of the hydrosilylated PB block was already demonstrated in the preliminary i nvestigation on the hydrosilylated PB homopolymer which formed stable monolayers for surface pressures as high as 40 mN/m. Such a behavior differs significantly from the PB block of the (PBb -PEO)3 star block copolymer which is much more hydrophobic and aggregates above the water surface. When the hydrosilylated star block copolymer was reacted under isobaric conditions for 10 h at 2 mN/m (Figure 5-21B), a clear phase separation between the cross-linked PB mate rial (yellow areas) and the PEO chains (dark areas) was observed, with an average height of about 2 nm for the cross-linked domains. However, it is only for surface pressures equal or higher than 6 mN/m that true PEO pores are trapped within the PB network (Figure 5-21D). As the surface pressure is further increased, the average PEO pore size decreases (Figures 5-21D, 5-21E, 5-21F, and 5-21G) to reach a morphology with very small PEO pores ( = 9 mN/m; Figure 5-21G). For even higher surface pressures such as 15 mN/m (Figure 5-21H), the cross-linked PB covers the entire surface with the PEO pores barely visible. This is in good ag reement with the fact that, at 10 mN/m, the PEO chains are pushed inside the water subphase. This was confirmed by cross-section analysis which showed that the monolayer cross-linked at 15 mN/m, with the PEO chains dissolved in the aqueous subphase underneath the PB network, is much smoother (smaller signal amplitude,

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121 Figure 5-22B) than the one cros s-linked at 6 mN/m (Figure 5-22A) with the PEO segments still present at the interface. The aver age sizes of the PEO pores were roughly determined from the power spectral densities (PSD) (Figures 5-22C and 5-22D) of the AFM images.225 The wavelengths corresponding to th e peaks in the PSD plots give the aver age distance between nearest neighbor PB doma ins for the monolayer transferred at 5 mN/m ( 180 nm) and the average PEO pore size for the monolayers transfe rred at 6, 9, and 15 mN/m. This characteristic pore size decreases from 130 nm for = 6 mN/m down to 40 nm for = 9 mN/m (Figure 522C). The PSD curves of the images of the LB films transferred at 7 and 8 mN/m were not included for easier visualization, but the averag e PEO “pore” sizes were equal to 46 and 42 nm, respectively. For surface pressures higher than 10 mN/m, no maxima were observed in the PSD plots, which is in good agreement with the fact th at the PEO pores could hardly be seen for such surface pressures as shown in Figure 5-21H. It can be concluded from this AFM analysis that the cross-linking reaction takes place homogeneously on the water surface, allowing the formation of a 2D network with PEO pores of controllable sizes by simply adjusting the polymerization surface pressure. Another experiment to illustrate the possibili ty to retain a specific morphology after crosslinking was attempted. A (PB(Si(OEt)3)b -PEO)3 monolayer was cross-linked at 9 mN/m for 10 h (pH = 3.0) and transferred onto mica. A second tr ansfer of the same cross-linked material was performed after barrier expansion back to 2 mN /m. As shown in Figure 5-23, the two LB films have similar morphologies, with only a slight increase in PEO pore size after monolayer expansion.

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122 Figure 5-21. AFM topographic images of the (PB(Si(OEt)3)b -PEO)3 star block copolymer LB films. (A): t = 0 h. (B), (C), (D), (E), (F), (G), and (H): t = 10 h. The images are 2 x 2 m2. Figure 5-22. (A) and (B): Cross-section analys is of Figures 5-21D and 5-21H. (C): PEO pore size versus surface pressure plot. (D): PSD plots of Figures 5-21C, 5-21D, 5-21G, and 5-21H.

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123 Figure 5-23. AFM topographic images and corre sponding cross-sections of the (PB(Si(OEt)3)b PEO)3 star block copolymer LB films cr oss-linked at 9 mN/m (pH = 3.0, t = 10 h) and transferred at 9 and 2 mN/m. The images are 2 x 2 m2. A final experiment was designed to prove that when the cross-linking reaction is carried out above 10 mN/m, the PEO chai ns are irreversibly dissolved and held into the aqueous subphase, underneath the cross-linked PB networ k. After cross-linking the monolayer at 20 mN/m ( t = 10 h, pH = 3.0), the barriers were fully expanded and the isotherm of the cross-linked monolayer was recorded as shown in Figure 5-24 (blue curve). The PEO-related phase transition (pseudoplateau) is no longer present, which confir med that the PEO chains could not readsorb at the interface during monolayer e xpansion. A control experiment was carried out by recording the isotherm of a monolayer cross-linked below the surface pressure corresponding to the PEO aqueous dissolution (5 mN/m, Fi gure 5-24, red curve). As expected, the PEO pseudoplateau is still present (even after several compression-expansion hysteresis cy cles), which confirms that it is possible at high surface pressure ( > 10 mN/m) to freeze the “bilayer” conformation of the cross-linked material consisting of a cross-lin ked PB layer covalently attached to a PEO sublayer.

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124 Figure 5-24. Surface pressure-MMA isothe rms of the hydrosilylated (PB(Si(OEt)3)b -PEO)3 star block copolymer cross-linked at 5 and 20 mN/m (pH = 3.0, t = 10 h). 5.3 Conclusions The main objective of this study was to pr opose a new and general method to synthesize a novel 2D polymeric nanomaterial consisting of a continuous cross-linked PB network containing PEO pores of controllable sizes. To reach that goal, a novel (PB(Si(OEt)3)b -PEO)3 three-arm star block copolymer was synt hesized by hydrosilylating the PB pendant double bonds of a (PBb -PEO)3 three-arm star block copolymer with triethoxysilane. Spontan eous hydrolysis and condensation under acidic conditions of the triethoxysilane pe ndant groups of the (PB(Si(OEt)3)-

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125 b -PEO)3 three-arm star block copolymer allowed th e easy cross-linking of the PB segments directly at the A/W interface without any additive s or reagents. This strategy permits to control the size of the PEO pores simply by adjusting the surface pressure during cross-linking as shown by AFM imaging of the LB films. Further characterization of these 2D cro ss-linked networks will be required (gas permeability, small angle scattering, and 2D visc ometry) to understand the benefits provided by the A/W interfacial self-assembly compared to other conventional solution self-adsorption or other processes. At stake is the possibility to use 2D self-organization as a means to construct materials with anisotropic structures, to reproduc ibly engineer such structures, and to target defined functions with these materials. In addition, such alkoxysilane-containing monolayers could also be easily grafted ont o inorganic surfaces (glass support such as silicon wafer) through covalent bonds to synthesize polyme r/inorganic composite materials. 5.4 Experimental Methods 5.4.1 Materials and Instrumentation The synthesis of the PBb -PEO three-arm star block copolymers was previously reported.222 Toluene used in the hydrosilylation reacti ons was dried and distilled twice over CaH2 and polystyryllithium successive ly. The PB homopolymer ( Mn = 11,050 g/mol; Mw/ Mn = 1.04) (Polymer Source Inc.), triet hoxysilane (Aldrich, 99%), and platinum(0)-1,3-divinyl-1,1,3,3tetramethyldisiloxane complex (Karstedt cataly st, 3 wt % solution in xylene) (Aldrich, 99%) were used as received without further purification. 1H-NMR spectra were recorded on VarianVXR 300 MHz, Gemini 300 MHz, and Mercury 300 MHz using CDCl3 as the deuterated solvent. Chemical shifts are reported in ppm () downfield from tetramethylsilane (TMS) and referenced to residual chloroform (7.27 ppm). FTIR absorbance spectra were recorded on a Brker/Vector 22 FT/IR spectrometer. The samples were prepared by dissolving the

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126 hydrosilylated and non-hydrosilylated polymers in chloroform (C 1 mg/mL), and the resulting solutions were subsequently spr ead dropwise onto KBr pellets and allowed to dry under vacuum in a desiccator. 5.4.2 Langmuir Films Surface film characterization was accomplis hed by use of a Teflon Langmuir trough ( W = 150 mm and L = 679 mm) system (KSV Ltd., Finland) equipped with two moving barriers and a Wilhelmy plate for measuring surface pressure Between runs, the trough was cleaned with ethanol and rinsed several times with Millipore filtered water of 18 M .cm resistivity. The subphase temperature was maintained at 25 C through water circulating under the trough. Samples were typically prepared by dissolving 1 mg of polymer in 1 mL of chloroform and spread dropwise with a gastight Hamilton syring e on the Millipore water surface. For the surface property studies of th e non-hydrosilylated (PBb -PEO)3 star block copolymers, the chloroform was allowed to evaporate for 30 min to ensure no residual solvent remained, and the isotherms were subsequently recorded with barrier movement of 5 mm.min-1. For the surface property studies of the (PB(Si(OEt)3b -PEO)3 three-arm star block copol ymer and the triethoxysilanefunctionalized PB homopolymer, the isotherms were recorded after differe nt reaction times at zero pressure (pH = 3.0, barrie r compression speed of 100 mm.min-1). The isobaric experiments were carried out just after spre ading and after monolayer compressi on up to a surface pressure of 5 ((PB(Si(OEt)3b -PEO)3 three-arm star block copolyme r) or 10 mN/m (triethoxysilanefunctionalized PB homopolymer) fo r different subphase pH values. 5.4.3 Hydrosilylation of the PB Homopolymer In a flame and vacuum-dried three-neck flas k equipped with a magnetic stirrer, a reflux condenser, a dry argon inlet, and a heating mantle, 142 mg (1.28x10-5 mol) of linear PB ( Mn =

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127 11,050 g/mol) were freeze-dried and then dissol ved in 20 mL of dry toluene. Triethoxysilane (0.573 mL, 3.133x10-3 mol) and Karstedt catalyst (0.1 mL, 3 wt % solution in xylene) were then added, and the reaction was carried out under argon for 24 h at 80 C. At the end of the reaction, the solvent and the unreacted triethoxysilane were removed by evaporation under vacuum, and the hydrosilylated PB homopolymer was stored under dry argon (Crude product: Mn (1H NMR) = 33,200 g/mol; m = 135 mg). 1H NMR (ppm; CDCl3): 5.4 (bm, —CH2—C H =C H —CH2— and CH2=C H —CH—), 4.9 (b, C H2=CH—CH—), 3.8 (b, —CH2—Si(OC H2CH3)3), 2.0 (bm, — C H2—CH=CH—C H2— and CH2=CH—C H —), 1.5-0.7 (b, —CH2—Si(OCH2C H3)3, and CH2=CH—C(R)H—C H2—), and 0.3-0.7 (b, —C H2—Si(OEt)3). 5.4.4 Hydrosilylation of the (PB200b -PEO326)3 Three-Arm Star Block Copolymer In a flame and vacuum-dried three-neck flas k equipped with a magnetic stirrer, a reflux condenser, a dry argon inlet, and a heating mantle, 164 mg (2.17x10-6 mol) of (PB200b -PEO326)3 three-arm star block copolymer were freeze-drie d and dissolved in 15 mL of dry toluene. Triethoxysilane (0.285 mL, 1.562x10-3 mol) and Karstedt catalyst (platinum(0)-1,3-divinyl1,1,3,3-tetramethyldisiloxane complex, 0.1 mL, 3 wt % solution in xylene) were added, and the reaction was carried out unde r argon for 24 h at 80 C. At the e nd of the reaction, the solvent and the unreacted triethoxysilane were removed by evaporation unde r vacuum, and the product was stored under argon (Crude product: Mn (1H NMR) = 135,500 g/mol; m = 160 mg). 1H NMR (ppm; CDCl3): 5.4 (bm, CH2—C H =C H —CH2— and CH2=C H —CH—), 4.9 (b, C H2=CH— CH—), 3.8 (b, —CH2—Si(OC H2CH3)3), 3.6 (b, —C H2—C H2—O—), 2.0 (b, C H2—CH=CH— C H2— and CH2=CH—C H —), 1.5-0.9 (b, —CH2—Si(OCH2C H3)3, and CH2=CH—C(R)H— C H2—), and 0.3-0.8 (b, —C H2—Si(OEt)3).

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128 5.4.5 A/W Interfacial Cross-Linking Chloroform solutions (100 L, C = 1 mg/mL) of the (PB(Si(OEt)3)b -PEO)3 three-arm star block copolymer or of the hydrosilylated PB hom opolymer were spread dropwise with a gastight Hamilton syringe on the Millipore water subpha se at pH = 3.0. The monolayers were immediately compressed with barrier compression speed of 100 mm.min-1 and held at the desired surface pressure. In the case of the (PB(Si(OEt)3)b -PEO)3 three-arm star block copolymer, the cross-linking reaction was carried out for 10 h, and the cross-linked monolayers were subsequently transferred onto mica substrates (transfer rate = 1 mm/min) for further AFM characterization.. In the case of the hydrosilylated PB homopolymer, the Langmuir films were transferred onto freshly cleaved mica after cros s-linking at 10 mN/m for various reaction times. The LB films were dried in a dessicator for 24 h and subsequently scanne d in tapping mode with a Nanoscope III AFM (Digital Instruments, Inc. Santa Barbara, CA) using Nanosensors silicon probes (dimensions: T = 3.8-4.5 m, W = 27.6-29.2 m, L = 131 m). The images were processed with a second order flattening routine (Digital Inst ruments software). After crosslinking at 15 mN/m for at least 10 h to ensure completion of the cross-linking reaction, further compression of the resulting cross-linke d monolayers (cross-linked (PB(Si(OEt)3)b -PEO)3 three-arm star block copolymer or hydrosilylated PB homopolymer ) to a final area of ca. 2 x 15 cm2 led to the formation of multilayers ( 50 monolayers) that were easily removed with a spatula from the water surface and dried in a de ssicator for further FTIR study and solubility experiments.

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129 CHAPTER 6 ELECTROCHEMICAL AND SPECTROSCOPIC CHARACTERIZATI ON OF ORGANIC COMPOUND UPTAKE IN SILICA CORE-SHELL NANOCAPSULES 6.1 Introduction We recently prepared a series of nanocapsules ma de of core-shell silica spheres filled with a hydrophobic solvent, such as ethyl butyrate.49,226 Such nanocapsules are interesting objects in that the core is fluid and ther efore highly dynamic, while the she ll is solid and mesoporous, and appropriate surface modification leads to aqueous dispersions that are stable for months. In addition, the nanocapsules have sizes that can be controlled from some 60 to 600 nm, have extremely high interfacial area, have modera te polydispersity, and efficiently absorb hydrophobic compounds including drugs. These and othe r submicron-sized particles have shown a great potential for encapsulation of guest molecules. Representative examples of other systems include solid lipid nanoparticles (SLNs),227,228 nanoparticles,229-231 microspheres,232,233 liposomes,234,235 polymer vesicles,236 host-guest carriers,237,238 and shell cross-linked Knedel-like nanoparticles (SCKs).239,240 As introduced in Chapter 1, the current inve stigations are aimed to ward harnessing the encapsulation abilities of the nanocapsules for potential drug detoxification applications. Analogous controlled drug release applica tions often require the release of drug from the particle to be slow, zero order, and stable with time.232 Furthermore, the relative permeability of different species within the particle is not often consid ered. Drug detoxification, however, requires that the uptake of drug into the particle be as rapid as possibl e, and often further uptake beyond tens of minutes would be less desirable. Furthermore, the selectivity of the pa rticle to the drug should be as high as possible, and therefore the permeabili ty of the particle to substances of different molecular sizes and polarizabil ities should be minimal.

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130 In this chapter, we demonstrate that comb ined electrochemical (cyclic voltammetry) and optical (UV-vis and fluorescence sp ectroscopies) techniques provide a useful way to analyze the uptake of lipophilic substances by the nanocapsule s and like systems. The primary goal of this study is to fundamentally understand the host-gue st interactions and the physical properties driving the encapsulation process us ing simple analytical techniques. In this work, we therefore decided to use common organic probes suitable for optical and electrochemical experiments (iodine, Nile Red, ferrocene methanol, and fe rrocene dimethanol), because while UV-vis spectroscopy can be applied to a variet y of toxic drugs,241,242 fluorescence spectroscopy and electrochemistry are more restrictive techniqu es. The results discussed in this chapter will subsequently be of great importance in designing core-shell nanoparticulate systems for efficient and selective encapsulation applications. The essence of the electrochemical measuremen t is simply that any electroactive substance absorbed into a nanocapsule shows no or very little electrochemical activity, which leads to a decrease in the measured electrochemical signal upon encapsulation. The origin of this negligible electrochemical activity of the encapsulated probes compared to the ones remaining in solution can be rationalized by the following two theories Upon encapsulation, the electrochemical probe might stop behaving as an electroactive material b ecause the core and shell of the particle disrupt electron transfer processes. In fact, previous work has shown th at a compact monolayer of the size of only 12-14 CH2 groups was sufficient to block th e electron transf er between an electroactive substance and an electrode,243,244 while the shell thicknesses of our nanocapsules are much larger than this. Extensive work has al so been reported on dendrimers where the electron transfer was attenuated as the number of generations increases around redox-active cores.245,246 The other theory that would rationalize th e negligible electrochemical activity of the

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131 encapsulated probes relies on the fact that their diffusion coefficient toward the working electrode is essentially similar to the diffusion coefficient of the encapsulating agent as it was extensively shown for micellar systems.247-250 With encapsulating agents as big as the nanocapsules studied here, the apparent diffusi on coefficient of the encapsulated probes is sufficiently decreased, so their electrochemical signal can be neglected as quantitatively shown under Results and Discussion. Both theories l ead to the same experimental observation: a negligible influence of the encapsulated probes on the overall electrochemical signal. Nevertheless, additional experiments will be n ecessary to determine which one of these two theories best describes our en capsulating nanopar ticulate system. All experiments were performed following the same strategy. An aqueous solution containing a well-defined initial concentration of an electroactive or fluorescent probe was added to a given amount of nanocapsules. Since the el ectrochemical signal of the encapsulated probe molecules is negligible, the uptake can be m onitored relative to the elapsed time by the difference between the initial electrochemical signal and that after up take. When spectroscopy (fluorescence or UV-vis) was us ed instead of electrochemistry, the post-uptake location of the probe within the nanocapsules could be dete rmined by monitoring the signal maximum wavelength, which is strongly dependen t on the probe chemical environment. 6.2 Results and Discussion The nanocapsule synthesis is summarized in Figure 6-1. The goal of this work was to evaluate the efficiency of the uptake of va rious hydrophobic molecules and to analyze how the shell thickness influences the uptake kinetics. The samples prepared for the work thus had similar compositions in terms of octadecyltri methoxysilane (OTMS), lecithin, Tween-80, and ethyl butyrate amounts, but the tetramethoxysilane (TMOS) weight percent used was increased from 0.07 up to 0.88 wt %, allowing the synthe sis of nanocapsule samples with different shell

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132 thicknesses (Figure 6-2). The core and the shell sizes were characterized as detailed in the following, both by dynamic light scattering (DLS ) and transmission electron microscopy (TEM) after a preliminary staining step so that the co re and the shell of th e nanocapsules could be distinguishable. Figure 6-1. Oil-filled silica nanocapsule synthesis through in itial hydrophobic core formation followed by hydrophilic silica shell fo rmation after TMOS addition. Figure 6-2 Description of the nanocapsule samples prep ared using 0.07 wt % TMOS (a), 0.28 wt % TMOS (b), 0.44 wt % TMOS (c), and 0.88 wt % TMOS (d).

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133 6.2.1 Nanocapsule Characterization Figure 6-3 shows as an example the DLS results of the thin shell nanocapsule samples. Curve a, which represents nanocapsules prior to TMOS addition, shows two peaks. The one around 7-8 nm corresponds to the diameter of micelles arising from Tween-80 aggregation, and the other one around 40 nm corresponds to the oi l core diameter of the nanocapsules after microemulsion formation. Curve b corresponds to 0.07 wt % TMOS added to the microemulsion analyzed in curve a. The peak around 40 nm shifted to approximately 80 nm, showing shell formation ( 20 nm thick) upon TMOS addition. The peak around 7-8 nm disappeared because the samples have been dialyzed before the DLS measurement is run, showing that almost all the Tween-80 micelles have been removed. This is a particularly important point for the following study, because in the case micelles were present they could also be responsible for one part of the active molecules uptake, and therefore no sensible c onclusion could be drawn from it. In the rest of the study, any possible micelle influen ce has therefore been purposely avoided. Overall, the particle size analysis shows relativ ely narrow distributions and, as expected, a proportional relationship between the shell size and the amount of TMOS used, leading to nanocapsules diameters in the range of 80200 nm, according to the synthetic conditions. Figure 6-3. DLS results for the microemulsion im mediately after preparation (a) and the same solution after TMOS addition (0. 07 wt %) and dialysis (b).

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134 The nanocapsules were also characterized by TEM analysis. Figure 6-4 shows examples of particles with 0.07 wt % TMOS (a) and 0.88 wt % TMOS (b). The nanocapsule core has been stained with 1-dodecene and osmium tetroxide (OsO4). As a consequence, only the hydrophobic core absorbing 1-dodecene is stained and appears darker than the silica shell. We should note that, due to the high solubility of Tween-80 in ethyl butyrate, so me core stain also comes from the reaction between Tween-80 and OsO4. As shown in Figure 6-4, the nanocapsule characteristic sizes (core diamet er/shell thickness) are in good agreement with the DLS results. Figure 6-4. TEM micrographs of the 0.07 wt % TMOS nanocapsules (a) and of the 0.88 wt % TMOS nanocapsules (b). 6.2.2 Uptake Study Two types of electroactive molecules have been used for the study. Their choice was based on the fact that such probe molecules must show perfectly reversible re dox behavior over many cycles, must have a strong affinity for the orga nic phase inside the nano capsules, and yet must retain aqueous solubility sufficient for the initia l electrochemical measurem ents to be possible. Therefore, we decided to use ferrocene methanol and ferrocene dimethanol (Figure 6-5), since these simple probes are soluble in both organic solvents and water. Due to the presence of the

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135 hydroxyl groups, both ferrocenes may show a te ndency to bind revers ibly through hydrogen bonding to the nanocapsule silica sh ell, and not only to partition in the oil phase but also to reside partly in the silica shell. It has been pr eviously shown that the diffusion coefficients of these two molecules in hydrated Sol-Gel-derived glasses were onl y slightly decreased from the ones in solution with valu es in the range of 10-6 cm2/s.251 Therefore, in the presence of diffusiondriven encapsulation, even with the presence of specific interactions with the silica shell, fast uptake kinetics would be expected to be seen, be cause the average time for a molecule to diffuse through a few tens of nanometers (using the simple relationship252 2 / 1) 2 ( Dt d with t = time of the experiment, D = diffusion coefficient of the probe, and d = average distance travelled by the probe during t) is on the order of 10-6 s. Absorption and fluorescence spectroscopic studi es were also undertaken in order to supplement and confirm the electrochemical study. The two molecules chosen in this case were iodine and Nile Red (Figure 6-5). Because of thei r structures, they should have very low affinity for the silica shell and are therefore expected to partition strictly between the oil core and the aqueous solution. Because UV-vis and fluorescence measurements show a chemicalenvironment-dependent signal maximum, the shif t observed after nanocapsule solution addition to the iodine or Nile Red solution indicate s the environment where the probes end up after encapsulation. Figure 6-5. Chemical structures of ferrocene me thanol, ferrocene dimethanol, and Nile Red.

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136 6.2.2.1 Optical measurements results Figure 6-6 represents the UV-vis absorption sp ectra of iodine in various aqueous and organic environments. The measurements were recorded after addition of 1mL of a saturated iodine aqueous solution to given amounts of eith er nanocapsule or ethyl butyrate solutions. The large signal shift toward lower wavelengths (b lue shift) compared to the spectrum in water qualitatively indicates that the chemical environment of iodine significantly changes (becomes more hydrophobic) after addition of the nanocapsule solution, and that therefore a consequent uptake in the hydrophobic nanocapsule core took pl ace. However, test experiments have also been performed on a Tween-80 aque ous solution to appreciate the influence of this compound in the process. The overlap of th e iodine UV-vis curves in the presence of nanocapsules and Tween-80 indicates that Tween-80 alone was also capable of absorbing/encapsulating iodine in its hydrophobic micellar core (C18 chains), so that it is not very clear at this point if a separate layer of Tween-80 in the nanocap sules, Tween-80 dissolved in the organic solvent core, or the organic solvent core itself is effective in retaining iodine. Figure 6-6. UV-vis absorption spectr a of iodine in water solution (a), in nanocapsule solution (b), in Tween-80 aqueous solution (c), an d in ethyl butyrate solution (d).

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137 In another experiment, Nile Red was used as a fluorescent probe, because fluorescence is a more sensitive technique than UV-vis absorption. This classical dye is fluorescent and soluble in aqueous medium only at acidic pH values. Severa l fluorescence experiments have been carried out in order to check the uptake and the environment of th e dye after nanocap sule absorption. Fluorescence spectra of Nile Red were measured in acidic water solution, in nanocapsule solutions, in a Tween-80 aqueous solution, in ethyl butyrate solution, and on silica gel under various conditions as shown in Figure 6-7. Figure 6-7. Nile Red emission spectra in ethyl butyrate solution (a), in nanocapsule solution (b), in Tween-80 aqueous solution (c), in crushe d Xerogel dispersion in acidic water (d), on silica gel (e), and in acidic water solution (f). In this set of experiments, the dye can be se lective for comparison be tween the two types of silica environments, the acidic water, the Tween-80, and the ethyl butyrate. The data show that both the silica and the acidic water give the sa me fluorescence signal, which corresponds to the acidic form of Nile red. On th e other hand, in the presence of Tween-80 or the nanocapsules, a fluorescence signal typical of Nile Red in an organic environmen t is obtained, which proved the complete uptake of the dye by both the Tween-80 micelles and the nanocapsules. It should be

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138 noted that Nile Red in the na nocapsules is probabl y in a Tween-80 envir onment (on the inner shell wall) and not in the ethyl butyrate core, b ecause the spectrum is almost the same as in Tween-80 micelles and different from th at in the ethyl butyrate solution. 6.2.2.2 Electrochemical experiments Ferrocene methanol and ferrocene dimethanol upt akes were measured as a function of time by electrochemistry. As a preliminary experiment we determined the partition coefficients of these two compounds between ethyl butyrate a nd water by UV-vis spectroscopy (by stirring biphasic solutions with a given amount of ferro cene methanol or dimethanol and measuring the absorbance in the aqueous phase after stabi lization). As expected, ferrocene methanol and ferrocene dimethanol turned out to be more soluble in ethyl butyrate than in water, with partition coefficient values of 40 and 2.5, respectively. The experiments involved the use of cyclic voltammetry to evaluate changes in the concentration of free electroactive species. An example of a typical cyclic voltammogram recorded for ferrocene methanol is shown in Figure 6-8. Figure 6-8. Typical cyclic voltammogra m of ferrocene methanol in water.

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139 The peak potentials difference is around 60 mV As discussed in Ch apter 2, this shows that, at this potential scan rate (500 mV/s), ferrocene methanol and ferrocene dimethanol conversions remain reversible. The currents ther efore remain basically diffusion controlled, and the faradaic current ( I p, difference in intensity between the oxidation peak and the residual current) is given by the following Randles-Sevci k equation (6-1) previously introduced in Chapter 2, 2 / 1 2 / 1 2 / 3 5) 10 69 2 ( v ACD n Ip (6-1) where C is the concentration of the electroactive species, A is the surface of the working electrode in cm2, D is the diffusion coefficient of the electroactive species in cm2/s, is the potential scan rate in V/s, and n is the number of el ectrons transferred in the redox process. A n and are kept constant during the cyclic voltammetry scans, and therefore I p is directly proportional to D1/2C As mentioned in the introduction of this chapter, when the nanocapsules are added, the encapsulated molecules become either electrochemically inactive (electron transfer cannot occur within distances larger than 5-10 nm and the particle shell is always larger) or have an apparent diffusion coe fficient sufficiently low so that th e signal intensity arising from the encapsulated probes can be neglected. The diffusion coefficient D for spherical particles is given by the following Stokes-Einstein equation (6-2) previously introduced in Chapter 2, R T k DB6 (6-2) where kB is the Boltzmann constant ( kB =1.38 10-23 m2 kg s-2 K-1), T is the temperature in K, is the solution viscosity in P, and R is the particle radius in m. When this equation is applied to our nanocapsules of 40-100 nm radius, the diffusi on coefficient is calculated in the range (26)x10-8 cm2/s, which is a factor 102-103 smaller than a typical diffusion coefficient for a single molecule like ferrocene methanol or dimethanol (in the range 10-5-10-6 cm2/s). The signal from

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140 the nanocapsules is therefore e xpected to be beyond detections, even in the unlikely case of a non-negligible electron transfer with in the shell. It should be noted here that the reversibility of the uptake in principle could be observable and studied, upon conversion of most of the ferrocene into ferricinium ion inside the water. Ho wever, this requires extensive electrolysis of the remaining ferrocene inside the water, which is complicated, not only because it implies using a cell allowing both analytical electrochemistry a nd extensive electrolysis, but above all because the stability of the ferri cinium ion is not sufficient, especi ally in water (i t slowly undergoes nucleophilic attack from water). The electrochemical signal th erefore quantitatively decrease s in proportion to the uptake, and the aqueous concentration can be calculated by applying the relationship I p C Since the initial concentration in electroactive compounds in the solution is accurately known, it is not necessary to know the exact electrode paramete rs that would make the measurements less precise. The relative variation of the concentr ation, and therefore th e electroactive compound uptake inside the nanocapsules, is directly obtained. The partition coefficients between Tween80 and water for ferrocene methanol and ferrocene dimethanol could not be measured because of the high viscosity of Tween-80 an d its high solubility in water. Nonetheless, we suppose that, analogous to the behavior observed in the spectroscopy experiment s above, the Tween-80 present in the oil core might increase the uptake. The ferrocene methanol uptakes for the nanoc apsule samples introduced earlier are shown in Figure 6-9. The normalized aqueous concentra tion decrease is plotted versus time. All the nanocapsule samples show significant decrease in the ferrocene methanol concentration, and as might have been expected, the overall uptake is roughly increased with increasing nanocapsule concentration (Figure 6-10). Cont rary to the iodine and the N ile Red spectroscopic experiments

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141 where the signal shift was almost instantaneous upon addition of the nanocapsule solutions, we see slower uptake kinetics for the larger shel ls, indicating a shell-size influence. Ferrocene methanol interacts with the silica shell thr ough hydrogen bonding interactions in a phenomenon similar to that observed in classical column chromatography via an adsorption/desorption mechanism. As previously reported, such a me chanism reduces the diffusion coefficient in the silica shell, but in order to observe simply a slower diffusion-driven uptake, the diffusion coefficient in the nanocapsule sh ell should in theory be reduced by several additional orders of magnitude (in the 10-12-10-13 cm2/s range). Such a large decrease of the diffusion coefficient in the shell is unlikely for a classical diffusion mechanism; therefore, other additional shellthickness-dependent parameters must be involved. Figure 6-9. Uptake of ferrocene methanol versus time in 0.07 wt % TMOS nanocapsule solution (b1, total concentration: 5.9 wt %; b2, total concentration: 6.2 wt %), in 0.28 wt % TMOS nanocapsule solution (c, total concen tration: 1.9 wt %), in 0.44 wt % TMOS nanocapsule solution (d, total concentratio n: 1.9 wt %), and in 0.88 wt % TMOS nanocapsule solution (e, total concentration: 4.9 wt %). (a) Control experiment in the absence of nanocapsules. The dotted lines are provided to highlight the trends.

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142 Figure 6-10. Plot of normalized aqueous concentration of ferrocen e methanol after uptake in 0.07 wt % TMOS nanocapsule solution (b1, total concentration: 5.9 wt %; b2, total concentration: 6.2 wt %), in 0.28 wt % TMOS nanocapsule solution (c, total concentration: 1.9 wt %), in 0.44 wt % TMOS nanocapsule solution (d, total concentration: 1.9 wt %), and in 0.88 wt % TMOS nano capsule solution (e, total concentration: 4.9 wt %). (a) Control expe riment in the absence of nanocapsules. While further quantitative analysis is some what difficult to make, support from this interpretation comes from the fact that the only cases where appreciable slower kinetics are seen in Figure 6-9 are the two cases where the la rgest amount of TMOS was introduced in the synthesis solution (curves d and e that respectivel y correspond to nanocapsule samples with 0.44 and 0.88 wt % TMOS), and therefor e where thicker shells were obtained. For these two samples, it takes approximately 200-300 s before the aqueous concentration of ferro cene methanol levels off, whereas the thermodynamic equilibrium is reach ed almost instantaneously for the other three samples with thinner silica shells (curves c an d b that respectively correspond to nanocapsule samples with 0.28 and 0.07 wt % TMOS). To further investigate silica shell/alcohol inte ractions, we carried out similar experiments with ferrocene dimethanol. This substance displays a similar electroactivity with a slight shift in

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143 potential (which does not influen ce this type of measurement) compared to ferrocene methanol, but contains two alcohol groups making it not only more hydrophi lic but above all much more likely to interact with the silica shell. The uptake results are presented in Figure 6-11. As expected from the results with ferrocene methanol much slower kinetics were observed for all the nanocapsule samples, including those with thin silica shells. Moreover, compared to the results for ferrocene methanol, the overall uptake is lower, this due to a higher hydrophilicity of ferrocene dimethanol. However, one must notice th at this is not true for the 0.28 wt % TMOS nanocapsule sample, where the uptake is higher for ferrocene dimethanol although the reason for this result is not very clear Moreover, based on the partition coefficients mentioned before, the uptake seems surprisingly larg e. Even though the concentrati on of ferrocene dimethanol is probably smaller in the nanocapsu le core, we suppose the signifi cant uptake observed might be due to increased interactions between the polar ferrocene dimethanol OH groups and the hydrophilic silica shell, which woul d be significantly reduced in the case of ferrocene methanol. The ferrocene dimethanol uptake is therefore more complicated to quantit atively analyze because of the combined influence of the oil core and th e silica shell. The influe nce of the silica shell on the overall uptake was already shown to some ex tent by the results fo r ferrocene methanol (Figure 6-10), where samples d (0 .44 wt % TMOS, total concentratio n: 1.9 wt %)) and e (0.88 wt % TMOS, total concentration: 4.9 wt %) showed increased encapsulation efficiencies compared respectively to samples c (0.28 wt % TMOS, total concentration: 1.9 wt %) and b1 (0.07 wt % TMOS, total concentration: 5.9 wt %). While th is study gives some hint of the silica shell influence on the uptake efficiency and kine tics, complete understandi ng of the encapsulation mechanism will require further investigation.

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144 Figure 6-11. Uptake of ferrocene dimethanol versus time in 0.07 wt % TMOS nanocapsule solution (b, total concentration: 5.9 wt %) in 0.28 wt % TMOS nanocapsule solution (c, total concentration: 1.9 wt %), in 0.44 wt % TMOS nanocapsule solution (d, total concentration: 1.9 wt %), and in 0.88 wt % TMOS nano capsule solution (e, total concentration: 4.9 wt %). (a) Control experi ment in the absence of nanocapsules. The dotted lines are provided to highlight the trends. As stated earlier, all the nanocapsule samp les were extensively dialyzed in order to eliminate, as much as possible, potential contam inants besides the nanocapsules, and especially residual Tween-80 micelles. Uptake measurements were also carried out on Tween-80 aqueous solutions to check if Tween-80 micelles could influence the uptake. Micellar envelopes have been shown not to influence th e electron transfer between th e encapsulated species and the working electrodes, and therefore only the d ecrease in the diffusion coefficient of the encapsulated species influences the electrochemical signal.247-250 As determined by DLS, the radius of Tween-80 micelles is approximately 4 nm, which leads from the Stokes-Einstein equation to a diffusi on coefficient around 6x10-7 cm2/s. It is a factor 10-102 times smaller than the diffusion coefficient of single molecules li ke ferrocene methanol and ferrocene dimethanol; therefore, encapsulation by Tween -80 micelles can easily be seen with cyclic voltammetry as

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145 shown in Figures 6-12 and 6-13. Nevertheless, the diffusion coefficient after encapsulation by Tween-80 micelles is not sufficiently decreased to completely neglect the influence of the encapsulated molecules on the overall peak intensity as it was the case for the nanocapsules. The normalized aqueous concentration of ferrocene methanol and ferrocene dimethanol versus Tween-80 concentration was plotted assuming that the molecules encapsulated by the micelles do not contribute at all to the ove rall electrochemical signal. Th e real aqueous concentration is slightly smaller than the one reported, and it s accurate determination is possible but would require knowing both the diffusion coefficients of Tween-80 mice lles and of the two probes. However, the encapsulation kinetics are instanta neous in the case of ferrocene methanol, and very fast (although slightly discer nible) in the case of ferrocene dimethanol. The different uptake kinetics observed with the nanocapsules, in add ition to the fact that all the suspensions were extensively dialyzed, allows us to state unamb iguously that the uptake observed and discussed before was due only to the nanocapsules. Figure 6-12. Uptake of ferrocene methanol vers us time in 0 wt % Tween-80 aqueous solution (a), in 2 wt % Tween-80 aqueous solution (b), in 4 wt % Tween -80 aqueous solution (c), in 6 wt % Tween-80 aqueous soluti on (d), and in 8 wt % Tween-80 aqueous solution (e). The dotted lines are pr ovided to highli ght the trends.

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146 Figure 6-13. Uptake of ferrocene dimethanol ve rsus time in 0 wt % Tween-80 aqueous solution (a), in 2 wt % Tween-80 aqueous solution (b), in 4 wt % Tween -80 aqueous solution (c), in 6 wt % Tween-80 aqueous soluti on (d), and in 8 wt % Tween-80 aqueous solution (e). The dotted lines are pr ovided to highli ght the trends. 6.3 Conclusions In this chapter, a detailed spectroscopi c and electrochemical study of the uptake mechanism of organic chemicals by core-shell na nocapsules was presented. This method shows promise as a means to determine the efficiency and the kinetics of th e uptake process. From these experiments, we can conclude that an im portant factor in the in corporation of organic chemicals in the core of the nanocapsules is th e diffusion through the si lica shell, which acts analogously to a chromatographing layer. However, even in the least fa vorable case studied, the incorporation time is short and the nanocapsules are efficient removers of large amounts of organic compounds present in an aq ueous solution. This confirms th e expected efficiency of the nanocapsules to remove toxic substances from body liquids, and therefore their potential in detoxification media.

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147 6.4 Experimental Methods 6.4.1 Nanocapsule Synthesis Synthesis of the core-shell nanocapsules was ca rried out according to the previous work reported by our group.226 OTMS (0.09 g, Gelest Inc.), lecithin (0.05 g, Alfa Aesar), and Tween80 (2.8 g, Aldrich Chemical Co.) were used as the surfactants, and ethyl butyrate (0.4 g, Aldrich Chemical Co.) was used as th e hydrophobic oil phase. Microemulsion formation was carried out by adding those four chemicals in saline soluti on (9 wt % NaCl aqueous solution, 26 mL) under heating (70 oC) with vigorous stirring for at least 8 h. OTMS polycondensati on was carried out at pH = 3 using a 0.5 M HCl aqueous solution and by vigorous stirring for 30 min. The shell thickness was controlled by reactin g various amounts of TMOS (0.02 g-0.26 g, Gelest Inc.) with the unreacted silanol groups of the OTMS molecu les present at the microemulsion surface. This last step was carried out after the pH of th e nanocapsule solution was increased to neutral conditions (pH 7.4) with 0.5 M NaOH and 0.5 M HE PES-buffered solutions. To remove unreacted OTMS and TMOS, free Tween-80, and le cithin, extensive dialysis was performed using Spectra/Por molecular porous membrane t ubing with a molecular weight cutoff of 6-8000 Da. 6.4.2 Transmission Electron Microscopy For the TEM experiments, the nanocapsule core was doped with 1-dodecene (Aldrich Chemical Co.). After deposition of a droplet on a carbon-coated ni ckel grid (Electron Microscopy Sciences) and evapor ation of the water in a desicca tor, the nanocapsule core was stained by exposure to OsO4 vapors (Aldrich Chemical Co.) in a closed container fo r at least 4 h. All TEM images were obtained using a Hitachi H-7000 inst rument at 75 kV.

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148 6.4.3 Particle Size Analysis Size analysis was performed before TMOS addi tion, and after reacti on and dialysis. This allowed determination of the core diameter an d shell thickness for every nanocapsule sample prepared. All samples were diluted to avoid inte rparticle aggregation and filtered prior to size analysis using 0.22 m pore size filters (Fisher Scientific). DLS was used to follow changes in particle sizes with a Precision Detectors PDDL S/CoolBatch+90T instrument. The data were analyzed with the Precision Deconvolve32 Program. Measurements were taken at 20 C at a 90 scattering angle using a 632 nm laser source. Fina l sizes were obtained from the average of at least five reproducible results. 6.4.4 Spectroscopy Measurements UV-vis absorption spectra were reco rded on a UV-vis Varian CARY 500 spectrophotometer, and excitation and fluoresce nce emission spectra were measured on a SPEX Fluorolog-3 (Jobin-Yvon). A right -angle configuration was used. The optical density of the samples was checked to be less than 0.1 to avoid reabsorption artifacts. Iodine and Nile Red are both commercially available (Aldrich Chemical Co .). The Nile Red stock solution was prepared by placing 2 mg of Nile Red in 5 mL of methanol, filtering with a 0.22 m Millipore filter, and adding the saturated Nile Red methanol solu tion to 100 mL of acidic water (pH = 1.2). UV-vis absorption spectra were recorded af ter mixing thoroughly 1 mL of a saturated iodine aqueous solution with reference solutions consisting of 2 mL of water, 2 mL of ethyl butyrate, 2 mL of water with 1 drop of Tween-80, and 1 mL of water with 1 mL of nanocapsule solution. Fluorescence spectra were recorded on Nile Red after excitation at 595 nm. For the measurements involving the three aqueous soluti ons (nanocapsules, Tween-80 aqueous solution, and acidic water), fluorescence sp ectra were recorded after mixing 0.5 mL of the Nile Red stock

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149 solution with 0.5 mL of nanocapsule solution in 2. 0 mL of water, 1 drop of Tween-80 in 2.5 mL of water, and 2.5 mL of acidic water, respectively. For the fluor escence spectrum of Nile Red in ethyl butyrate, 3 mL of ethyl bu tyrate was mixed with 0.5 mL of the Nile Red stock solution. The ethyl butyrate layer was then pipetted into a glass cuvette, and the fluorescence spectrum of the Nile Red in ethyl butyrate was recorded. Fo r the silica gel experiments, a saturated solution of Nile Red in ethanol was mixed with 2 g of s ilica gel and the excess solvent was evaporated to adsorb Nile Red onto the silica gel. Finally, the Xerogel was prepared by allowing the drying of a mixture of 12.5 mL of Nile -Red-saturated ethanol, 5.6 mL of tetraethoxysilane (Aldrich Chemical Co.), and 0.9 mL of water with pH 3. 4. The resulting gel was subsequently crushed and placed in acidic water. 6.4.5 Electrochemistry Experiments The electrochemical studies were perfor med using an EG&G PAR 273 potentiostat, interfaced to a PC computer. Cyclic voltammetr y experiments were carried out in a threeelectrode 10 mL electrochemical cell. The work ing electrode used was a 1 mm diameter disk vitreous carbon electrode polished on a diamond pa ste covered rotating disk (Presi) prior to each experiment. The auxiliary elec trode was a platinum wire, an d the reference electrode (Ag+/Ag electrode filled with 0.01 M AgNO3) was checked versus ferrocene as recommended by IUPAC. In our case, E(Fc+/Fc) = 0.045 V in acetonitrile with 0. 1 M tetraethylammoni um perchlorate. Ferrocene methanol and ferrocene dimethanol were purchased from Aldrich Chemical Co., and lithium perchlorate was purchased from Fluka (puriss). The ferrocene methanol and ferrocene dimeth anol aqueous solutions used contained 2x10-4 mol/L of either electroactive molecule and 10-1 mol/L lithium perchlorate used as the electrolyte. A typical uptake experiment was carried out as follows: an initial cy clic voltammogram is recorded for 5 mL of ferrocene methanol or ferro cene dimethanol solution in the electrochemical

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150 cell (potential scan rate = 500 mV/s). The encapsulating solution (1 mL of nanocapsule solution or Tween-80 aqueous solution) is added to the cell, zero time is defined at the point addition is complete, and the solution is stirred for 5 s with a magnetic stir bar. Further cyclic voltammograms are then recorded versus time a nd the faradaic current s are determined for uptake calculation. The faradaic current at t = 0 s was simply calculate d by dividing the faradaic current obtained in the initial cyclic voltamm ogram (before addition of the encapsulation solution is done) by the dilution factor (6/5 fo r our experiments). Cycl ic voltammograms were not recorded simultaneously with stirring because otherwise the Randles-Sevcik equation used in calculating the aqueous concentration of the pr obes during uptake would not be valid. The experimental data and the error bars plotted co rrespond respectively to th e average value and to the standard deviation obtained fr om three different measurements.

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151 CHAPTER 7 TOWARD SPECIFIC DRUG DETOXIFICA TION AGENTS: MOLECULARLY IMPRINTED NANOPARTICLES 7.1 Introduction As discussed in Chapter 1, drug toxic ity is a major health concern worldwide.253 Unfortunately, most life-threatening drug int oxications do not have specific antidotes to overcome the effects of many drugs. Therefore, in th e event of illicit drug uses, suicide attempts or iatrogenic complications, therapy is usually onl y restricted to stabilizing the patient. To reduce drug poisoning, it is only recently that a lot of e ffort has been put into exploring in depth the unusual properties provided by na notechnology science with the de sign of new nanosize objects that have the ability to reduce the bio-avai lability of toxic co mpounds within the body.34,254 Most toxic drugs are highly hydrophob ic and are therefore only s lightly soluble in aqueous environments such as in the blood stream. As a consequence, several nanosystems have been synthesized with the aim to encapsulate and isolate th e toxic drugs through hydrophobic interactions to signif icantly decrease their free blood con centration below toxic levels. Some examples reported in the literature explored for instance the potential of emulsionand microemulsion-based systems in sequester ing the toxic drugs inside hydrophobic oil cores.37,49,226,255 Other recent works investigated the possibility of binding the toxic drugs through interactions inside modified chitosan nanoparticles.256 When designing drugencapsulating systems for in-vivo drug detoxification applications, several properties have to be taken into consideration. As emphasized in Chap ter 1, the system should be smaller than the smallest capillaries (< 5 m) to move freely in the blood st ream, it should have fast (within seconds or minutes) and high encapsulation capaci ties, it should be non-t oxic (biocompatible), biodegradable (slowly enough so th e aqueous concentration of th e drug released in the blood

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152 stays below toxic levels), and, above all, it shou ld be specific to the ta rget drug to avoid side encapsulation of other undesired molecules present in the blood stream. In an attempt to design nanoparticulate systems with incr eased specificity and high encap sulation capacities, we report in this chapter our investigati ons on the potential for molecula rly imprinted nanoparticles to be used as encapsulating agents in drug detoxification therapy. The imprinting strategy in this work us es the non-covalent imprinting approach.73,257 The synthesis of polymers molecularly imprinted in the bulk with various toxic drugs has been extensively reported.69,258 Moreover, the possibil ity of synthesizing molecularly imprinted nanoparticles has been recently demonstrated.259 With a view toward in vivo drug detoxification applications, we report here for the first tim e the synthesis of nanoparticles molecularly imprinted with amitriptyline (Figure 7-1), which is a commonly used tricyclic antidepressant that may cause cardiac toxicity at high concentration, and the results of their uptake abilities in aqueous solutions under physiological pH conditions. Figure 7-1. Chemical structures of amitriptyline and bupivacaine. 7.2 Results and Discussion Miniemulsion polymerizations ha ve attracted much attention in the past because of their great potential in synthesizing nanosized spheres with a variety of properties and applications.260 Tovar and co-workers were to our knowledge the fi rst to report about the potential of miniemulsion polymerization to synthesize mol ecularly imprinted nan oparticles by the non-

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153 covalent technique, where they demonstrated that water sol uble binding monomers such as methacrylic acid (MAA) were quantitatively incor porated inside the nanoparticles, which is a crucial condition for an effici ent imprinting to take place.261 However, the density of the MAA groups was probably higher in the outer shell of the na noparticles, as previously described for other miniemulsion polymerizations involving water soluble monomers.262 This probably led to an increased binding efficiency, since the impr inted sites were mostly situated near the nanoparticle surface and therefore more easily a ccessible for the template molecules during the rebinding studies. In our molecularly imprinted nanoparticle synthesis, ethylene glycol dimethacrylate (EGDMA) was used as the hydrophobic crosslinker, MAA as the binding monomer, azobisisobutyronitrile (AIB N) as the oil-soluble radical in itiator, hexadecane as the highly hydrophobic agent preventing Ostwald Ripening,83 ethyl butyrate (EB) as the hydrophobic porogen, and amitriptyline as the template molecule. The relative molar amounts crosslinker/monomer/template during the imprinting step ranged around 20/4/1 which are commonly used ratios in molecular imprinting technology.263 It should be noticed that, to demonstrate the ability of amitriptyline-based molecularly imprin ted nanoparticles to be used as detoxification agents, we deliberately chose to vary only the amounts of cross-linker, monomer, and template as shown in Table 7-1. Amitripty line has non-negligible water solubility which makes it able to freely dissolve in aqueous systems such as in the blood stream. Nevertheless, amitriptyline is highly hydrophobic with reported part ition coefficient values of several thousands between 1octanol and water.264 Therefore, under our experiment al miniemulsion polymerization conditions, incorporation of amitr iptyline in the miniemulsion oil core during polymerization can

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154 be considered quantitative, making the imprintin g possible. The imprinting strategy is shown in Figure 7-2. Table 7-1. Loading compositions of the miniemulsions. Sample EGDMA MAA Amitriptyline hydrochloride MIP1 600 mg (3.03 mmol) N/A N/A MIP2 550 mg (2.77 mmol) 50 mg (0.581 mmol) N/A MIP3 500 mg (2.52 mmol) 100 mg (1.162 mmol) N/A MIP4 600 mg (3.03 mmol) N/A 50 mg (0.159 mmol) MIP5 550 mg (2.77 mmol) 50 mg (0.581 mmol) 50 mg (0.159 mmol) MIP6 500 mg (2.52 mmol) 100 mg (1.162 mol) 50 mg (0.159 mmol) 1/ crosslinking 2/ template, porogen and surfactant removal Template Binding monomer CrosslinkerRadical initiator Porogen Stabilizing surfactant Figure 7-2. The molecular imprinting st rategy in miniemulsion polymerization. The efficiency of the cross-linking reactio n was demonstrated by infra-red (FTIR) spectroscopy. Figure 7-3 show s the FTIR spectra of MIP1 and MIP3, and the FTIR spectrum of pure EGDMA before reaction is also included for comparison. The absorbances of the peaks at 1640 cm-1 (stretching vibration frequency of the alkenyl C=C double bonds) and at 3100 cm-1 (stretching vibration frequency of the alkenyl C-H single bonds) al most completely vanished for MIP1 and MIP3, indicating that the doubl es bonds of EGDMA and MAA were successfully

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155 consumed during the polymerization.265 It is also interesting to notice for MIP3 the appearance of a broad absorbance peak in the 3400-3600 cm-1 region that corresponds to the stretching vibration of O-H bonds from carboxy lic acid groups, which confirms the successful inclusion of the MAA monomers in the nanoparticle s during miniemulsion polymerization.266 Figure 7-3. IR absorbance spectra of EGDMA, MIP1, and MIP3. The apparent hydrodynamic diameters of the nanoparticles were determined by dynamic light scattering (DLS) just afte r miniemulsion polymerization a nd after high dilution to avoid interparticle aggregation. All the samples show m onodisperse distributions with average particle diameters around 220 nm 50 nm, independent of the nanocap sule composition. The DLS size distribution of MIP6 is shown as an example in Figure 7-4. The ability to design particles through miniemulsion polymerization with diameters in the nanometer range and with therefore large surface-to-volume ratios is essential for drug detoxification therapy, because it has been previously shown that increasing the availabl e contact surface by decr easing the size of the encapsulation entities significantly enhanced the uptake of toxic drugs, probably resulting from a surface adsorption phenomena. In the pr esent work, the amount of surfactant

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156 (dodecyltrimethylammonium bromide, DTAB) stabilizing the miniemulsion droplets during polymerization was not varied and was kept rela tively low to make particles with diameters around 200 nm. However, miniemulsion technology al lows accurate control of nanoparticle size by varying the amount of stabilizing surfactant us ed during polymerization.260 With a view toward increasing the available surface area for drug detoxification applications, synthesis of nanoparticles with smaller diameters could theref ore ultimately be achieved by increasing the amount of stabilizing surfactant. Figure 7-4. DLS size distribution of MIP6. Tapping mode atomic force microscopy (AFM) imaging of the nanoparticles deposited onto mica substrates confirmed the results obtained from DLS, with no change in particle size independent of the initial miniemulsion formulation. As an example, typical AFM images of MIP6 are presented in Figure 7-5. The nanoparticle s are again highly monodisperse in size, with an average measured diameter of 250 nm 50 nm, which is slightly larger than the average value obtained from DLS. As shown in Figures 7-5c (surface plot) and 7-5d (cross-section analysis), the nanoparticles tend to flatten upon adsorption on the mica substrate, which explains the slightly overestimated diameter value obtained fr om AFM characterization compared to DLS. It

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157 is also interesting to notice that AFM imagi ng of the nanoparticles was also possible after purification, drying, and resuspension by soni cation for 10 min in water with no apparent changes in size and morphology. Figure 7-5. Tapping mode topographi cal AFM images (a, b, and c) and cross-section analysis (d) of MIP6. MIP1, MIP2, and MIP3 were not molecularly imprinted with amitriptyline and were used as control experiments. Their bi nding studies for amitriptyline unde r physiological pH conditions (HEPES buffered saline solutions, pH 7.4) are presented in Figur e 7-6. All three samples can very efficiently bind amitriptyline as shown by the very high partition coefficient values indicated in the captions of Figure 7-6, and the amount of bound amitriptyline increases as the nanoparticle concentration is in creased. More interestingly, th e uptake non-negligibly decreases as the amount of MAA present in the nan oparticles increases. U nder physiological pH conditions, amitriptyline (pKa = 9.4)264b is present in the aqueous phase at approximately 99% in its protonated form, and the acid groups present on the nanoparticle surface or pore walls are

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158 mostly deprotonated. The results in Figure 7-6 clearly show that the up take is not driven by electrostatic interactions between the positiv ely charged amine of amitriptyline and the deprotonated and negatively charged carboxylic acid gr oups of the nanopartic les. In the case of non-imprinted nanoparticles, the uptake is dr iven by non-specific hydrophobic interactions between the nanoparticles and the hydrophobic aroma tic rings and aliphatic carbon chain of amitriptyline, which is likely adsorbed on the pore wa lls through its non-polar moiety with the protonated amine group facing the aqueous solution. The uptake being driven by hydrophobic interactions instead of hydrogen bondings or electrostatic interacti ons in water is well known and has already been described for other molecu larly imprinted polymers used for molecular recognition in aqueous conditions.267 This is not the case when bi nding studies are carried out in less polar organic solvents such as dichloromethane268 or toluene,269 since their dielectric constants are not as high as for water and do not significantly break polar host-guest interactions. Figure 7-6. Uptake of amitriptyline by the non-molecularly imprinted nanoparticles MIP1 ( Kp 1600), MIP2 ( Kp 1000), and MIP3 ( Kp 1100). The lines are provided to highlight the trends. Similar binding experiments of amitriptyline were carried out for the molecularly imprinted nanoparticle samples MIP4, MIP5, and MIP6 (Figure 7-7). MIP6 that does not contain any polar carboxylic acid gr oups has a high affinity for amitriptyli ne, so this confirms the results

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159 obtained previously for MIP1, MIP2, and MIP3, where it was observe d that the hydrophobic interactions play a sign ificant role in the binding. Neverthe less, as the amount of carboxylic acids in the molecularly imprinted nanoparticles is in creased, the uptake is significantly increased as well (partition coefficient values in captions of Figure 7-7), contrary to the non-imprinted nanoparticles. This clearly indicat es that, although polar interactio ns alone are obviously weaker than hydrophobic interactions in aqueous solutions the presence of specific and shape-persistent amitriptyline recognition sites fo rmed from the weak electrosta tic/hydrogen bonding interactions between MAA and amitriptyline during the imprin ting stage significantly increases the uptake, and consequently the nanocapsules binding specific ity. Prior to carrying out the binding studies and as indicated in the experime ntal section, the nanoparticles we re extensively washed at least five times with tetrahydrofuran (THF) until no residual amitriptyline coul d be detected by UVvis spectroscopy in the centrifugatio n supernatants. Nevertheless, it should be noticed that traces of amitriptyline probably remained after nanopart icle synthesis and template extraction in MIP4, MIP5, and MIP6 as shown by the slightly lower uptake (and partition coefficient value) of MIP4 compared to MIP1. Figure 7-7. Uptake of amitriptyline by th e nanoparticles molecularly imprinted with amitriptyline: MIP4 ( Kp 1200), MIP5 ( Kp 1800), and MIP6 ( Kp 2700). The lines are provided to highlight the trends.

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160 As a final experiment, binding studies were carried out with bupivacaine (Figure 7-1) on nanoparticle samples MIP4, MIP5, and MIP6 molecularly imprinted with amitriptyline. Bupivacaine (pKa = 8.1) is an amide class local an esthetic used in clinical medicine to provide local or regional anesthesia during surgical proc edures, and the necessity in reducing quickly the free concentration of bupivacaine has al so recently attracted much attention.49 The uptake experiments presented in Figure 7-8 and the partiti on coefficients provided in the figure captions confirmed, in the absence of specific imprinting, that the uptake is ma inly driven by hydrophobic interactions, with the nanocapsule samples containing polar carboxylic acid groups binding less efficiently bupivacaine molecules. Figure 7-8. Uptake of bupivacaine by the nanopar ticles molecularly imprinted with amitriptyline: MIP4 ( Kp 190), MIP5 ( Kp 120), and MIP6 ( Kp 120). The lines are provided to highlight the trends. 7.3 Conclusions We demonstrated in this chapter that mol ecularly imprinted nanoparticles prepared by simple miniemulsion polymerization can effi ciently encapsulate large amounts of hydrophobic toxic drugs such as amitriptyli ne or bupivacaine. The absence of template molecules during nanoparticle synthesis prevents the formation of specific binding sites, a nd as a consequence the uptake remains mainly driven by non-specific adsorption onto the nanoparticles through

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161 hydrophobic interactions. Neverthele ss, the combined presence of cross-linkable binding groups and template molecules during nanoparticle synthe sis allows the formation of specific binding sites that specifically increase the uptake. Th e ideal system for drug detoxification therapy requires very high uptake capabilities and 100% specificity. Optimization of a molecularly imprinted system can be achieved but requires playing with many vari ables, such as the molecular imprinting strategy (c ovalent or non-covalent), the polymerization method, or the amounts and identities of binding monomers, cro ss-linkers, and porogens.81 The purpose of this work was therefore to demonstrate with relativel y simple experimental conditions that molecular imprinting technology has great po tential for in-vivo drug det oxification therapy. Molecular recognition in water with molecu larly imprinted polymers started to be explored only very recently, with the ultimate goal to efficiently mimic host-guest interactions found in natural aqueous environments. Therefore, further investigations will be necessary to improve the specificity and decrease the non-specific hydro phobic binding of the molecularly imprinted nanoparticles in aqueous media under physiological pH conditions. With a view toward drug detoxification applica tions, future work should also include investigating the biodegradability of these water hydrolysable ester-b ased nanoparticles as well as their biocompatibility after preliminary surface modification with for inst ance tethered poly(ethylene oxide) chains.270 7.4 Experimental Section 7.4.1 Materials Ethylene glycol dimethacrylate and methacry lic acid were purchased from Aldrich Chemical Co. and were distille d under reduced pressure before use. Dodecyltrimethylammonium bromide, ethyl butyrate, amitriptyline hydrochl oride, bupivacaine hydrochloride, hexadecane, azobisisobutyronitrile, and HEPE S (4-(2-Hydroxyethyl)piperazine-1 -ethanesulfonic acid) were purchased from Aldrich Chemical Co. and were used as received without further purification.

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162 7.4.2 Nanoparticle Synthesis The nanoparticles were synthesi zed by traditional miniemul sion polymerization, following a previously reported method.261 The amounts of DTAB (10 mg 0.032 mmol), EB (100 mg, 0.86 mmol), hexadecane (30 mg, 0.13 mmol), and AIBN (12 mg, 0.073 mmol) we re kept constant, and only the amounts of EGDMA, MAA, and amitr iptyline hydrochloride in the miniemulsion formulations were varied as previously indica ted in Table 7-1. All the chemicals were mixed with 5 mL of Millipore filtered water in a 10 mL vial, vigorously stirre d for 1 h with a magnetic stir bar, and then sonicated for 5 min. The resulting opaque and milk-like solution was then transferred into a 5 mL round bottom flask, and th e radical polymerization was carried out in an oil bath for 20 h at 80 oC under vigorous stirring. The nanoparticles were subsequently centrifuged out of the solution (15 000 rpm, 1 h). They were then redispersed and centrifuged at least 5 times out of 50 mL of THF to remove the unreacted chemicals and amitriptyline template, and finally dried overnight under vacuum. 7.4.3 FTIR Spectroscopy FTIR absorbance spectra were recorded on a Brker/Vector 22 FT/IR spectrometer. The samples were prepared according to the followi ng procedure: the dry and purified nanoparticles were dispersed by sonication in TH F, and the solutions were subs equently spread dropwise onto KBr pellets and allowed to dry in a desiccator. 7.4.4 Particle Size Analysis Size analysis was performed on the nanopartic le solutions obtained after miniemulsion polymerization and after performing approximate ly a 1000 times dilution to avoid interparticle aggregation. DLS was used with a Precision De tectors PDDLS/CoolBatch+90T instrument. The data were analyzed with the Precision Deconv olve32 Program. Measurements were taken at

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163 20 C at a 90 scattering angle using a 632 nm laser so urce. Final sizes were obtained from the average of at least five reproducible results. 7.4.5 AFM Imaging AFM imaging of the nanoparticles was perfor med immediately after polymerization and after resuspension of the purified particles in Millipore filtered water. The nanocapsule concentrations were adjusted to approximately 0.1 mg/mL, and the samples were prepared by air drying (in a desiccator fo r at least 24h) a few drops of th e nanocapsule solutions deposited onto freshly cleaved mica. The films were subsequen tly scanned in tapping mode with a Nanoscope III AFM (Digital Instruments, Inc., Santa Barbara, CA) using silicon probes (Nanosensor dimensions: T = 3.8-4.5 m, W = 26-27 m, L = 128 m). The images were processed with a second-order flattening routine. 7.4.6 Uptake Experiments For binding studies, various amounts of purified and dried nanoparticles were resuspended by sonication in 8 mL of 250 M (amitriptyline) or 1,500 M (bupivacaine) HEPES-buffered saline solutions (pH = 7.4, C(HEPES) = 20 mM, C(NaCl) = 8 g/L). After vigorous stirring for 24 h, the nanoparticles were removed by centrifugation (15 000 rpm, 1 h), and the decrease in amitriptyline or bupivacaine concentrations in the supernatants was quantified by UV-vis spectrosco py after preliminary establishment of calibration curves (absorbance versus concen tration) at respectively = 238 and 264 nm. All the data plotted result from the average of 3 distinct uptake measur ements, and the error bars correspond to the standard deviations. The part ition coefficient values ( Kp) of the drugs between the nanoparticles and the aqueous phase were estimated by dividi ng the number of moles of amitriptyline or

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164 bupivacaine encapsulated per gram of nanoparticles by the number of moles remaining in the aqueous solution per gram (i.e ., mL) of water after uptake.

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165 CHAPTER 8 CONCLUSIONS AND PERSPECTIVES In this dissertation, the investigations on th e A/W interfacial behavior of various block copolymers in Chapters 3, 4, and 5, as well as the synthesis and characte rization of nanoparticles for drug detoxification purposes in Chapters 6 and 7 were presented. As discussed in Chapter 3, the PSb -P t BA dendrimer-like block copolymer aggregated into circular surface micelles for low surface pressu res before collapsing around 24 mN/m. The PSb PAA dendrimer-like block copolymer formed st able Langmuir monolay ers only under acidic conditions and aggregated into circular surf ace micelles at low pressure, before aqueous dissolution of the PAA segments followed by aggr egation of the micella r PS cores took place around 5 mN/m. The aggregation numbers for both dendrimer-like block copolymers were estimated around 3-5 dendrimer-like block copolymer s per circular surface micelle. These rather low values compared to the results reported in th e previous literature for other architectures and chain lengths confirmed the tremendous influen ce of molecular architec ture on the 2D surface micelle formation of block copolymers. As discussed in Chapter 4, the interfacial behavior of PEOb -PCL block copolymers was, similarly as for PSb -PtBA and PSb -PAA block copolymers, also strongly dependent on the architecture. For the PEOb -PCL five-arm stars, only one phase transition around 13-14 mN/m corresponding to collapse and crystallization of the PCL segments was observed, whereas two additional PEO-related phase tran sitions (aqueous dissolution at 6.5 mN/m and brush formation at 10.5 mN/m) could be observed for the linear sa mples. Therefore, while the work presented in Chapters 3 and 4 gave some hint of the inte resting interfacial properties of these block copolymers, additional investigations on other sa mples with different architectures and chain lengths are necessary for a better fundamental understa nding of the influence of block copolymer

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166 architecture on the A/W interfaci al self-assembly. Brewster angl e microscopy investigations will also be necessary on the PCL-based block copo lymers in the high surface pressure region to determine if the PCL crystals observed by AFM imag ing in the LB films were formed directly at the A/W interface or if significant additional PC L crystallization took place during transfer. In Chapter 5, we took advantage of th e surface activity of hydrosilylated PBb -PEO threearm star block copolymers to synthesize at the A/W interface cross-linked polybutadiene twodimensional networks with PEO domains of controllable sizes trapped within, through polycondensation of triethoxysilan e pendant groups under acidic conditions. This novel and general method to cross-link in 2D polydiene blocks should easily be applied in the future to a variety of other polydiene-based block copolymers for the synthe sis of well-defined 2D crosslinked patterns. In Chapter 6, to quantify the drug encapsulation selectivity of oil-filled silica nanocapsules consisting of a hydrophobic liquid co re and a silicate shell, a se ries of electrochemical and spectroscopic measurements was performed, and the nanocapsules efficiently and rapidly removed large amounts of organic compounds presen t in aqueous solutions The silica shell was shown to act similarly as a chromatographing layer, but this does not lead yet to enough selectivity to avoid encapsulation of undesired molecules present in the blood stream. Additional nanocapsules should therefore be de signed with for instance differe nt oil-cores or silica shells with controllable pore sizes complementary to the target toxic drugs. With a view toward increasing specificity in drug detoxification therapy, a series of molecularly imprinted nanoparticles was synthesi zed by the non-covalent a pproach as described in Chapter 7, and the encapsulation specificity was studied through rebinding experiments. These nanoparticles are ideal ca ndidates for in-vivo drug detoxificati on applications since they were

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167 able to encapsulate large amounts of toxic drugs with some specificity under physiological pH conditions. In addition to investigating their bi ocompatibility and biodegr adability properties, future work on the molecularly imprinted nan oparticles should primarily focus on improving their specificity using other formulations to decrease nonspecific hydrophobic binding.

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184 BIOGRAPHICAL SKETCH Thomas J. Joncheray was born in Angers, Fr ance, on May 4, 1980. After graduating from high school in July 1998 (Lyce David dÂ’Angers), he pursued a two-year course of higher education in physics, chemistry, and mathemat ics (Lyce Bergson, Ange rs), allowing him to enter in September 2000 the Graduate School of Chemistry and Physics of Bordeaux (ENSCPB), France, where he obtained his masterÂ’s diploma. In July 2002, he moved to the University of Florida in Gainesville for his doctoral studies to investigate the air/water interfacial selfassembly of amphiphilic block copolymers and to synthesize nanoparticles for drug detoxification applications w ith Prof. Randolph S. Duran.