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Chemical Characterization of Mass-Selected Ions by Infrared Multiple Photon Dissociation Spectroscopy

Permanent Link: http://ufdc.ufl.edu/UFE0042491/00001

Material Information

Title: Chemical Characterization of Mass-Selected Ions by Infrared Multiple Photon Dissociation Spectroscopy
Physical Description: 1 online resource (201 p.)
Language: english
Creator: MINO,WARREN K,JR
Publisher: University of Florida
Place of Publication: Gainesville, Fla.
Publication Date: 2011

Subjects

Subjects / Keywords: DISSOCIATION -- FRAGMENTATION -- INFRARED -- MASS -- METHIONINE -- MULTIPLE -- PHOTON -- SPECTROMETRY -- SPECTROSCOPY -- TRYPTOPHAN
Chemistry -- Dissertations, Academic -- UF
Genre: Chemistry thesis, Ph.D.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract: Infrared multiple photon dissociation (IRMPD) spectroscopy is a powerful tool in identifying ion structures in mass spectrometry. In recent years, most IRMPD studies have been conducted at free electron laser (FEL) facilities, which offer tunability and high spectral brightness over the mid-IR range (500-2000 cm-1). Here, we implement a tunable benchtop optical parametric oscillator (OPO) laser in combination with trapping mass spectrometers to carry out IRMPD spectroscopy in the hydrogen stretching range (3000-4000 cm-1). In the Penning trap of a Fourier transform ion cyclotron resonance mass spectrometer, more weakly bound metal-chelated amino acid complexes can be successfully photodissociated. For a series of group II metals (Mg2+ ? Ba2+) complexed with the amino acids tryptophan (Trp) and methionine (Met), the O-H and N-H stretching vibrations readily allow distinction between the zwitterionic (Z) (i.e., NH3+-CHR-CO2-) and charge solvated (C) (i.e., NH2-CHR-COOH) forms of the amino acid (where R denotes the side chain). It is thus determined that for the M2+(Trp)2 dimers, the smaller cations favor the Z form. Conversely, for the M2+(Met)2 dimers, the opposite trend is observed. These trends are complemented by quantum-chemical calculations to rationalize the findings. It is proposed that the bulky indole side chain in tryptophan accounts for the unusual trend in favoring Z structures for smaller cations. The IRMPD yield is shown to be increased by irradiating the ion cloud with a second non-resonant CO2 laser at a fixed frequency of 10.6 micrometer, following OPO laser irradiation. Moreover, the trapping voltages of the Penning trap can be adjusted to improve the overlap between the ion cloud and the laser beam, and hence enhance the IRMPD yield. These approaches are found to be particularly useful in boosting the IRMPD yield of weaker modes. Nonetheless, photodissociation of more strongly-bound ions is found to be much more challenging. A custom-built mass spectrometer is presented, where the ions are irradiated in a reduced pressure (10-5 mbar) ?Paul-type? quadrupole ion trap (QIT). The compact ion cloud is subjected to focused laser beams. Comparison of IRMPD of protonated tryptophan in the Penning and Paul traps shows that required laser irradiation times are considerably shorter and that weaker modes become visible. Furthermore, the fragmentation pathways of protonated tryptophan in collision-induced dissociation conditions are interrogated by IRMPD spectroscopy, assisted by quantum-chemical calculations. The loss of NH3 is shown to be mediated by a nucleophilic attack from carbon C3 on the indole side chain. The subsequent CH2CO loss product is also structurally characterized. These results demonstrate that strongly-bound ions and reaction products from collision-induced dissociation in particular, can now be routinely characterized by IRMPD spectroscopy using a benchtop infrared laser. It is expected that these developments will make the technique of IRMPD spectroscopy more accessible to the wider mass spectrometry community, as opposed to being limited to a few user facilities.
General Note: In the series University of Florida Digital Collections.
General Note: Includes vita.
Bibliography: Includes bibliographical references.
Source of Description: Description based on online resource; title from PDF title page.
Source of Description: This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility: by WARREN K MINO.
Thesis: Thesis (Ph.D.)--University of Florida, 2011.
Local: Adviser: Polfer, Nicolas Camille.

Record Information

Source Institution: UFRGP
Rights Management: Applicable rights reserved.
Classification: lcc - LD1780 2011
System ID: UFE0042491:00001

Permanent Link: http://ufdc.ufl.edu/UFE0042491/00001

Material Information

Title: Chemical Characterization of Mass-Selected Ions by Infrared Multiple Photon Dissociation Spectroscopy
Physical Description: 1 online resource (201 p.)
Language: english
Creator: MINO,WARREN K,JR
Publisher: University of Florida
Place of Publication: Gainesville, Fla.
Publication Date: 2011

Subjects

Subjects / Keywords: DISSOCIATION -- FRAGMENTATION -- INFRARED -- MASS -- METHIONINE -- MULTIPLE -- PHOTON -- SPECTROMETRY -- SPECTROSCOPY -- TRYPTOPHAN
Chemistry -- Dissertations, Academic -- UF
Genre: Chemistry thesis, Ph.D.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract: Infrared multiple photon dissociation (IRMPD) spectroscopy is a powerful tool in identifying ion structures in mass spectrometry. In recent years, most IRMPD studies have been conducted at free electron laser (FEL) facilities, which offer tunability and high spectral brightness over the mid-IR range (500-2000 cm-1). Here, we implement a tunable benchtop optical parametric oscillator (OPO) laser in combination with trapping mass spectrometers to carry out IRMPD spectroscopy in the hydrogen stretching range (3000-4000 cm-1). In the Penning trap of a Fourier transform ion cyclotron resonance mass spectrometer, more weakly bound metal-chelated amino acid complexes can be successfully photodissociated. For a series of group II metals (Mg2+ ? Ba2+) complexed with the amino acids tryptophan (Trp) and methionine (Met), the O-H and N-H stretching vibrations readily allow distinction between the zwitterionic (Z) (i.e., NH3+-CHR-CO2-) and charge solvated (C) (i.e., NH2-CHR-COOH) forms of the amino acid (where R denotes the side chain). It is thus determined that for the M2+(Trp)2 dimers, the smaller cations favor the Z form. Conversely, for the M2+(Met)2 dimers, the opposite trend is observed. These trends are complemented by quantum-chemical calculations to rationalize the findings. It is proposed that the bulky indole side chain in tryptophan accounts for the unusual trend in favoring Z structures for smaller cations. The IRMPD yield is shown to be increased by irradiating the ion cloud with a second non-resonant CO2 laser at a fixed frequency of 10.6 micrometer, following OPO laser irradiation. Moreover, the trapping voltages of the Penning trap can be adjusted to improve the overlap between the ion cloud and the laser beam, and hence enhance the IRMPD yield. These approaches are found to be particularly useful in boosting the IRMPD yield of weaker modes. Nonetheless, photodissociation of more strongly-bound ions is found to be much more challenging. A custom-built mass spectrometer is presented, where the ions are irradiated in a reduced pressure (10-5 mbar) ?Paul-type? quadrupole ion trap (QIT). The compact ion cloud is subjected to focused laser beams. Comparison of IRMPD of protonated tryptophan in the Penning and Paul traps shows that required laser irradiation times are considerably shorter and that weaker modes become visible. Furthermore, the fragmentation pathways of protonated tryptophan in collision-induced dissociation conditions are interrogated by IRMPD spectroscopy, assisted by quantum-chemical calculations. The loss of NH3 is shown to be mediated by a nucleophilic attack from carbon C3 on the indole side chain. The subsequent CH2CO loss product is also structurally characterized. These results demonstrate that strongly-bound ions and reaction products from collision-induced dissociation in particular, can now be routinely characterized by IRMPD spectroscopy using a benchtop infrared laser. It is expected that these developments will make the technique of IRMPD spectroscopy more accessible to the wider mass spectrometry community, as opposed to being limited to a few user facilities.
General Note: In the series University of Florida Digital Collections.
General Note: Includes vita.
Bibliography: Includes bibliographical references.
Source of Description: Description based on online resource; title from PDF title page.
Source of Description: This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility: by WARREN K MINO.
Thesis: Thesis (Ph.D.)--University of Florida, 2011.
Local: Adviser: Polfer, Nicolas Camille.

Record Information

Source Institution: UFRGP
Rights Management: Applicable rights reserved.
Classification: lcc - LD1780 2011
System ID: UFE0042491:00001


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Full Text

PAGE 12

m/z m/z

PAGE 16

Introduction

PAGE 17

Amino Acids

PAGE 18

Protein Identification

PAGE 19

Edman Degradation

PAGE 20

Mass Spectrometry

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Am ino Acid and Peptide Identification Mass Spectrometry (MS)

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m /z) m/z m/z Electrospray i onization (ESI)

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Tandem mass spectrometry m/z

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Infrared multiple photon dissociation ( IRMPD )

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Infrared Multiple Photon Dissociation Spectroscopy Overview

PAGE 31

Introduction Fourier Transform Ion Cyclotron Resonance Mass Spectrometry History = q m B

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m/z m/z

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Fourier Transform Ion Cyclotron Resonance Theory Cyclotron m otion = = = m q B = + = = = =

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= m/z 4.7 2 ( 205 1. 661 10 /1. 602 10 = 351 = m/z d =

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A(t) ( ) = = ( ) = m/z m/z Mass detection d m/z =

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y Trapping m otion z = m q a Vtra pMagnetron m otion

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= + = Space charge effects = 1 1 4 /

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= "= Fourier Transform Ion Cyclotron Resonance Instrumentation

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Ion optics and vacuum s ystem = kB T d p

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Magnet m/z Analyzer cell

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Data s ystem Instrumentation O peration

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m/z

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m/z

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Quadrupole Mass Filter, Quadrupole Ion Trap, Time of Flight Mass Spectrometer Quadrupole Mass Filter Theory

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U V 0=U+ Vcos ( t) + ( + cos ) =0 ( + cos ) =0 = [ 2 cos 2 ] a q = =

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= = U V m/z m/z m/z a q a q 2U V a q m/z m/z a vs. q r0 q m/z m/z a q m/z 21. 6022 10 5000 0. 908 1. 661 10 (8.5 10)(2 10) =0. 37 /

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Quadrupole Ion Trap ,= ( r 2z) ( cos ) =0 ( cos ) =0 a q

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= 2 = = 2 = U U az U qz qz m/z V m/z

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Time of Flight Mass Spectrometry E m/z el Ek in = = = e z U m v v = t m/z s

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= ; = m/z = Optical Parametric Oscillator Lasers

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History

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Optical Parametric Oscillator Theory = + Nonlinear optics = E 0

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( ) = (0) I x = ( / ) = cos T F d n0, It I0= T

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= ( ) + ( ) + ( ) + = k k= k n

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Periodic poling Resonance cavity

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scan lock

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OS 4000 Alignment

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OS 4000 Operation

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Carbon D ioxide Lasers Carbon Dioxide Laser Operation

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(

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q B q B v

PAGE 74

Introduction

PAGE 76

Procedure Materials

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Mass Spectrometry and Ion Spectroscopy

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e.g.

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Calculations

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Results and Discussion Experimental Optimization

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. Ba 2+ Tryptophan Monomer Complex m/z

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[]+ [ ]+[+ ] M X vs.

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Alkaline Earth Tryptophan Dimer Series

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.

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Ba 2+ Tryptophan Dimer Complex

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vs.

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Ca 2+ Tryptophan Dimer Complex

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Metal Binding Effects on Z Stabilization

PAGE 92

Conclusions

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I nt J. Mass Spectrom.

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Int. J. Mass Spectrom.

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vs.

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Int.. J. Mass Spectrom.

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Int. J. Mass Spectrom.

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Int. J. Mass Spectrom.

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Int. J. Mass Spectrom.

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Introduction

PAGE 105

Experimental Materials Mass Spectrometry and Pho todissociation yield = ln[1 -{

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+Int_precursor)}]. Calculations

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Results and Discussion Ba2+ Methion ine Monomer Complex

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Alkaline Earth Methionine Dimer Series

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Mg2+ Methionine Dimer Complex

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Ca 2+ Methionine Dimer Complex

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Ba 2+ Methionine Dimer Complex Comparison of Methionine and Tryptophan

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Conclusions

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Complex Bond Distance in Angstroms Me O Me N Me -S Mg 2+ 2.05 Met 2.43 2.56 Ca 2+ 2.35 Met 2.51 2.91 Sr 2+ 2.49 Met 2.7 0 N/A Ba 2+ 2.68 Met 2.91 N/A

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Introduction m/z

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Experimental Materials Mass Spectrometry and Ion Spectroscopy

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Penning trap Custom built instrument equipped with a q uadrupole ion trap m/z m/z

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m/z

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m/z

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m/z m/z

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Calculations

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Results and Discussion Laser S et up in the Penning trap

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Effect of Trapping Condition on IRMPD

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Dual laser IRMPD yield

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Protonated Tryptophan IRMPD Spectrum in the Penning Trap

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Protonated Tryptophan IRMPD Spectrum in the Quadrupole Ion Trap

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Collision induced dissociation of TrpH + m/z m/z

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IRMPD of the [Trp+H NH m/z 3]+ Fragment Ion

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IRMPD of the [Trp+H NH 3CH2CO]+ Fragment Ion m/z m/z

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Conclusions m/z

PAGE 148

J. Phys. Chem. Lett.

PAGE 152

Signal Wavelength / N m Signal Wavenumber / cm Idler Wavelength / -1 nm Idler Wavenumber / cm -1 1715.091 5830.594 2802.768 3567.902 1720.431 5812.497 2788.623 3585.999 1721.231 5809.795 2786.524 3588.701 1723.188 5803.197 2781.410 3595.299 1727.355 5789.198 2770.622 3609.298 1728.341 5785.895 2768.089 3612.601 1729.865 5780.798 2764.188 3617.698 1730.434 5778.897 2762.737 3619.599 1733.043 5770.197 2756.112 3628.299 1733.439 5768.879 2755.112 3629.617 1734.697 5764.696 2751.940 3633.801 1738.859 5750.898 2741.530 3647.599 1739.373 5749.198 2740.253 3649.298 1739.767 5747.896 2739.276 3650.600 1740.009 5747.097 2738.676 3651.400 1741.494 5742.196 2735.005 3656.300 1745.293 5729.697 2725.687 3668.799 1745.872 5727.797 2724.276 3670.699 1747.183 5723.499 2721.090 3674.997 1747.489 5722.497 2720.349 3676.000 1748.528 5719.096 2717.834 3679.400 1751.315 5709.995 2711.128 3688.501 1752.082 5707.495 2709.292 3691.001

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0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 0 2 4 6 8 10IRMPD YieldTrapping Potenial (V) 0.2 0 0.2 0.4 0.6 0.8 1 1.2 0 2 4 6 8 10 12 14 16IRMPD Yield Irradiation Time (s) OPO Alone OPO and CO2 Irradiation

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band position cm-1assignment TrpH + 3555 carboxylic acid OH stretch 3500 indole NH stretch 3340 asymmetric NH3+ stretch 3195, 3140, 3090, 3050 NH3+ stretches [Trp+H NH 3 ] + 3560 carboxylic acid OH stretch 3425 indole NH stretch 3125 CH stretch [Trp+H NH 3 CH 2 CO] + 3600 OH stretch 3440 indole NH stretch

PAGE 158

m/z J. Phys. Chem. Lett.

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B3LYP m052x MP2 Hartrees ZPE kj mol -1 G FE kj mol -1 Hartrees ZPE kj mol -1 G FE kj mol -1 Hartrees ZPE kj mol -1 G FE kj mol -1 TrpH + Fig 5 12 A 686.76174 0.000 0.000 686.68491 2.765 0.627 682.56524 4.012 3.355 B 686.76170 0.536 0.536 686.68443 1.405 3.880 682.56500 2.045 2.024 C 686.76097 2.114 2.114 686.68620 0.000 0.000 682.56420 0.000 0.000 D 686.75890 7.341 7.341 686.68252 8.845 7.848 682.56080 7.073 13.503 Fig 5 13 A 686.76174 0.000 0.000 686.68491 2.765 0.627 682.56524 4.012 3.355 B 686.75379 20.426 20.426 686.67804 21.177 20.702 682.55584 17.588 23.422 C 686.75075 28.274 27.219 686.67280 34.525 31.981 682.55469 N/A N/A D 686.75024 29.734 29.734 686.67360 32.244 31.104 682.55435 N/A N/A TrpH+ NH 3 Fig 5 -16 A 630.13190 81.782 81.645 B 630.15989 9.757 9.848 C 630.16351 0.000 0.000 D 630.13598 72.561 72.810 Fig 5 -18 A 630.17946 42.491 46.327 B 630.17822 40.385 46.311 TrpH + NH3 CH2 CO Fig 5 -19 A 477.52127 0.000 0.000 477.46255 0.000 0.000 B 477.51846 6.664 6.364 477.45994 7.126 7.273 C 477.51690 10.788 10.056 477.45841 10.691 9.930 D 477.51198 23.370 22.816 477.45841 24.601 24.349

PAGE 160

m/z J. Phys. Chem. Lett.

PAGE 161

m/z m/z m/z m/z m/z

PAGE 162

m/z m/z m/z J. Phys. Chem. Lett.

PAGE 163

m/z J. Phys. Chem. Lett.

PAGE 164

m/z m/z m/z J. Phys. Chem. Lett.

PAGE 165

m/z J. Phys. Chem. Lett.

PAGE 166

m/z J. Phys. Chem. Lett.

PAGE 167

Introduction Slow Heating Techniques slow heating slow heating

PAGE 168

Disulfide Bond Cleavages in Mass Spectrometry m/z

PAGE 169

tocin ring tail Rational e for Experiments Experimental

PAGE 170

Results and Discussion Nomenclat ure a b c x y z

PAGE 171

tocin ring Product Ions From CID Spectra b/y tocin ring b/y tocin ring

PAGE 172

y4 y4 vice versa Neutral l oss f rom the precursor ion (1) b/y b/y

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Fragmentation from the peptide backbone t ail (2) b/y b6 b7b8 y3 y 3 b6 b6 y3 y3 b6Cleavage of the disulfide b ridge (3) tocin ring b2b4b5y5 y7

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y8 tocin ring b6 b4b5 y8 Loss of internal amino acids through b/y fragmentation (4) b8

PAGE 175

Con clusions b6/y3 tocin ring tocin ring

PAGE 177

J. Am. Soc. Mass Spectrom.

PAGE 184

J. Mass Spectrom

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Peptide Assignment fragments (no.) Assignment fragments (%PII) 1 (neutral loss) 2 (tail b/y ) 3 (ring b/y ) 4 (internal loss) Peptide Percentage of total ion intensity

PAGE 189

J. Am. Chem. Soc. 1998 120 J. Am. Soc. Mass Spectrom. 2001 12 Proc. Natl. Acad. Sci. USA 2004101 Biochim. Biophys. Acta 2006 1764 Mass Spectrom. Rev. 1998 17 Meth. Enzymol. 2005402 J. Mass Spectrom. 2004 39 Mass Spectrom. Rev. 200524 Anal. Chem. 199466 J. Am. Chem. Soc. 1978100 Laser Chem. 1984, 5, J. Am. Chem. Soc. 1985 107 J. Am. Chem. Soc. 1990 112 Phys. Chem. Chem. Phys. 2000 2 Phys. Chem. Chem. Phys. 2007 9 Biochemistry 1999 Science 2006 312 Electrophoresis 199819

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Trends Biotechnol. 1999 17 Acta Chem. Scand. 1950 4 Meth. Enzymol. 1973 27 Science 1989 246 Anal. Chem. 1988 60 Anal Chem. 199163 Nat. Rev. Mol. Cell Biol. 20045 Rapid Commun. Mass Spectrom. 2009 23 Curr. Opin. Struct. Biol. 2003 13 J. Am. Chem. Soc. 2002124 Proc. Natl. Acad. Sci. USA 2000 97 J. Am. Soc. Mass Spectrom. 200314 Instrumental A nalysis 2007 Med Res Rev 199919 Chem. Biol. 2000 7 Science 1999284 Mass Spectrom. Rev. 1990 9 Mass Spectromet ry: Principles and Applications; 2005

PAGE 191

Rapid Commun. Mass Spectrom. 1991 5 Anal. Chem 200173 J. Chem. Phys. 1976 64 Anal. Chim. Acta 2000 406 Tandem Mass Spectrometry ; 1983 Anal. Chem. 1985 57 Sov. Phys. Dokl 1971 16 J. Chem. Phys. Lett. 1979 63 J. Am. Chem. Soc. 1979101 Phys. Rev. Lett. 1978 40 Annu. Rev. Phys. Chem. 1994 45 Phys. Rev. Lett. 1977 38 J. Am. Chem. Soc. 1982 104 J. Phys. Chem. 1993 97 J. Am. Chem. Soc. 1998 120 Rev. Sci. Instrum. 200576 Mass Spectrom Rev 200928 Phys. Rev. 1932 40

PAGE 192

Phys. Rev. 1951 82 Rev. Sci. Instrum. 1965 36 Math. Comp 196519 Chem. Phys. Lett. 1974 26 J. Chem. Phys. 1979 71 Mass Spectrom. Rev. 1998 17 Comput. Chem. 1983 7 J. Am. Soc. Mass Spectrom. 1993 4 Rev. Mod. Phys. 1990 62 J. Mass Spectrom. 1996 31 Anal. Chem. 1984 56 Int. J. Mass Spectrom. Ion Process. 1983 54 Anal. Chem. 200880 1956 1960 Theory and Application of Mathieu Functions 1962 Mass Spectrom. Rev. 1986 5 Int. J. Mass Spectrom. Ion Process. 1998 172 Z. Naturforsch. Teil A 1953 8 Quadrupole Storage Mass Spectrometry 1989 Rapid Commun. Mass Spectrom. 199812

PAGE 193

Int. J. Mass Spectrom. 2000 200 Rapid Commun. Mass Spectrom. 200014 Practical Aspects of Io n Trap Mass Spectrometry: Chemical, Environmental, and Biomedical Applications 1995 Phys. Rev. 1946 69 Anal. Chem. 1959 31 J. Am. Soc. Mass Spectrom. 1993 4 Phys. Rev. Lett. 1961 7 Proc. IRE 1962 50 Appl. Phys. Lett. 19657 Quantum Electron. 1969 5 Phys. Rev. 1962 127 J. Expt. Theor. Phys. 1963 16 Appl. Phys. Lett. 1965 6 Phys. Rev. Lett. 1965 14 J. Opt. Soc. Am. B 1993 10 J. Opt. Soc. Am. B 1991 8 J. Opt. Soc. Am. B 1998 15 J. Opt. Soc. Am. B 1995 12 Opt. Lett. 199621 Opt. Lett. 1997 22 Opt. Lett. 1998 23

PAGE 194

Science 1999 286 Opt. Lett. 1999 24 2007 Proc. IEEE 1969 57 Nature 1960187 Nonlinear O ptics J. Opt. Soc. Am. B 1995 12 Opt. Lett. 1995 20 Appl. Phys. Lett. 1970 17 Quantum Electron. 1992 28 Opt. Mater. 199911 Rev. Sci. Instrum. 194617 Appl. Phys. B 1983 31 BioEssays 2000 22 Science 1998280 J. Biol. Chem. 2005 280 Biochemistry 1999 38 Biochemistry 1995 34 Biophys. J. 2000 79 J.Phys. Chem. A 2009 113

PAGE 195

Int J. Mass Spectrom. 2006 254 Mass Spectrom. Rev. 2009 28 Mass Spectrom. Rev. 2009 28 J. Phys. Chem. A 2009113 J. Am. Chem. Soc. 2004 126 J. Phys. Chem. A 1999 103 J. Am. Chem. Soc. 2006 128 Phys. Chem. Chem. Phys. 20068 Chem. Eur. J. 2002 8 J. Phys. Chem. A 2007 111 J. Am. Chem. Soc. 2005 127 Int. J. Mass Spectrom. 2003227 J. Phys. Chem. B 2003 107 J. Phys. Chem. A 2002 106 J. Phys. Chem. A 2005 109 J. Am. Chem. Soc. 2005 127 Int. J. Mass Spectrom. 1999 185 187 Angew. Chem. Int. Ed. 2004 43

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J. Phys. Chem. A 2008 112 J. Phys. Chem. A 2008 112 J. Am. Chem. Soc. 2007 129 J. Am. Chem. Soc. 2007 129 J. Phys. Chem. A 2009 113 Phys. Chem. Chem. Phys. 2010 12 J. Am. Chem. Soc. 2007 129 J. Phys. Chem. A 2008112 Int. J. Mass Spectrom. 2009 283 J. Am. Chem. Soc. 2008 130 J. Am. Chem. Soc. 2005 127 Angew. Chem. Int. Ed. 2006 45 Science 2007 316 Science 2005 308 J. Phys. Chem. A 2002 106 Int. J. Mass Spectrom. 2008272 Int. Rev. Phys. Chem. 199716 J. Chem. Phys. 2006 125

PAGE 197

J. Phys. Chem. A 2009113 J. Am. Chem. Soc. 2009131 Int. Revs. Phys. Chem. 2009 28 Phys. Ch em. Chem. Phys. 2010 12 J. Am. Chem. Soc. 1989 111 J. Phys. Chem. 1993 97 Gaussian 03, Revision B.03 2004. J. Am. Chem. Soc. 1995 117 J. Mass Spectrom. 2005 40 Int. J. Mass Spectrom. Ion Process. 1990 101 Int. J. Mass Spectrom. 2004235 J. Am. Chem. Soc. 1999 121 Int J. Mass Spectrom 2010 297 Annu. Rev. Biochem. 196635

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J. Biol. Chem. 1966 241 Angew. Chem. Int. Ed. Engl. 1971 10 Annu. Rev. Biochem 1972 41 Annu. Rev. Biochem. 197241 Biochemistry 1977 16 FEBS Lett. 1973 35 N ucl. I nstrum. M eth. A 2003507 P. N atl. A cad. S ci. USA 200299 J. Am. Chem. Soc. 2009 131 J. Am. Soc. Mass Spectrom. 2010 21 J. Am. Chem. Soc. 2003 125 J. P hys. Chem. A 2008 112 J. Am. Chem. Soc. 2007129 Int. J. Mass Spectrom. 2010 297 J. Comput. Chem. 2011, 32, J. Phys. Chem. A 2007 111 Mass Spectrom. Rev. 2009 28 J. Am. Chem. Soc. 2007 129 J. Am. Soc. Mass Spectrom. 200920

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J. Am. Chem. Soc. 2009 131 Chem. Phys. Chem. 2009 10 J. Am Chem Soc 2009 131 Int J. Mass Spectrom 2000 200 J. Am Soc Mass Spectrom 200415 J. Phys. Chem A 2004 108 J. Am Soc Mass Spectrom 2004 15 Anal. Chim Acta 1991246 Org. Mass Spectrom. 198924 J. Chem. Phys. 1992 96 Rapid Commun. Mass Spectrom. 199913 J. Am Chem Soc 1995 117 Int. J. Mass Spectrom. 2002 219 Mass Spectrom. Rev. 200322 J. Am. Soc. Mass Spectrom. 2003 14 J. Am. Soc. Mass Spectrom. 19901 Bioessays 1988 8 J. Am. Soc. Mass Spectrom. 2002 13 Int J. Mass Spectrom 2000 203

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J. Mass Spectrom. 200742 Crit Rev Neurobiol 1996 10 J. Am. Chem. Soc. 2005127 Eur J. Mass Spectrom 2004 10 2003 Biomed. Mass Spectrom 1984 11 Annu. Rev. Biochem. 1992 61