Publications

Books and Book Chapters

M. J. Charles; G. L. Glish, Review of Modern Ion Trap Research, in Practical Aspects of Ion Trap Mass Spectrometry, Vol. III, R.E. March, J.F.J. Todd, eds. CRC Press, Boca Raton, Fl., 1995, pp. 90-118.

S. A. McLuckey; G. J. Van Berkel; D. E. Goeringer; G. L. Glish, Electrospray Ionization, in Practical Aspects of Ion Trap Mass Spectrometry, Vol. II, R.E. March, J.F.J. Todd, eds. CRC Press, Boca Raton, Fl., 1995, pp. 89-141.

K. L. Busch; G. L. Glish; S. A. McLuckey, Mass Spectrometry/Mass Spectrometry: Techniques and Applications of Tandem Mass Spectrometry,VCH Publishers, Inc.: New York, 1988, 333pp.

Refereed Journal Publications

Glish, Gary L.; Vachet, Richard W. The basics of mass spectrometry in the twenty-first century, Nature Reviews Drug Discovery , 2(2), 140-150 (2003).

Ray, Kenneth L.; Glish, Gary L. Matrix-assisted laser desorption/ionization-boundary-activated dissociation of peptide ions in a quadrupole ion trap, International Journal of Mass Spectrometry, 222(1-3), 75-83 (2003)

Raska, Christina S.; Parker, Carol E.; Huang, Cai; Han, Jun; Glish, Gary L.; Pope, Marshall; Borchers, Christoph H. Pseudo-MS3 in a MALDI orthogonal quadrupole-time of flight mass spectrometer, Journal of the American Society for Mass Spectrometry , 13(9), 1034-1041.(2002)

Chen, Paul H.; Richardson, Susan D.; Krasner, Stuart W.; Majetich, George; Glish, Gary L.Hydrogen Abstraction and Decomposition of Bromopicrin and Other Trihalogenated Disinfection Byproducts by GC/MS, Environmental Science and Technology , 36(15), 3362-3371.(2002)

Raska, Christina S.; Parker, Carol E.; Dominski, Zbigniew; Marzluff, William F.; Glish, Gary L.; Pope, R. Marshall; Borchers, Christoph H. Direct MALDI-MS/MS of phosphopeptides affinity-bound to immobilized metal ion affinity chromatography beads, Analytical Chemistry , 74(14), 3429-3433.(2002)

Asam, Michael R.; Glish, Gary L. Collision-induced signal enhancement (CISE): the use of boundary activation to effect non-resonant CISE, Journal of the American Society for Mass Spectrometry , 13(6), 650-658.(2002)

Brodbelt, Jennifer S.; Glish, Gary L., Focus on quadrupole ion traps, Journal of the American Society for Mass Spectrometry , 13(6), 587-588.(2002)

Danell, Allison S.; Glish, Gary L. Charge permutation reactions in beam type mass spectrometers, International Journal of Mass Spectrometry , 212(1-3), 219-227. CODEN: IMSPF8 ISSN: 1387-3806.(2001)

A. S. Danell; G. L. Glish Evidence for ionization-related conformational differences of peptide ions in a quadrupole ion trap, J. Am. Soc. Mass Spectrom., 12, 1331-1338 (2001).

A. H. Payne; G. L. Glish Thermally Assisted Infrared Multiphoton Photodissociation in a Quadrupole Ion Trap, Anal. Chem., 73, 3542-3548 (2001).

T. Lin; A. H. Payne; G. L. Glish Dissociation Pathways of Alkali-Cationized Peptides: Opportunities for C-terminal Peptide Sequencing, J. Am. Soc. Mass Spectrom., 12, 497-504 (2001).

A. H. Payne; G. L. Glish Gas-phase ion/ion interactions between peptides or proteins and iron ions in a quadrupole ion trap, Int. J. Mass Spectrom., 204, 47-54 (2001).

R. M. Danell; G. L. Glish A new approach for effecting surface-induced dissociation in an ion cyclotron resonance mass spectrometer: a modeling study, J. Am. Soc. Mass Spectrom., 11, 1107-1117 (2000).

S. A. Serron; W. S. Aldrich, III; R. M. Danell, T. J. Meyer Synthesis of Derivatized Amino Acids for the Study of Electron Transfer, Tetrahedron Letters, 41, 4039-4042 (2000).

A. H. Payne; J. H. Chelf; G. L. Glish C-terminal peptide sequencing using acetylated peptides with MSⁿ in a quadrupole ion trap, Analyst, 125, 635-640 (2000).

M. R. Asam; G. L. Glish Determination of the Dissociation Kinetics of a Transient Intermediate, J. Amer. Mass Spectrom., 10, 119-125 (1999).

T. Lin; G. L. Glish C-Terminal Peptide Sequencing via Multistage Mass Spectrometry, Anal. Chem., 70, 5162-5165 (1998).

M. R. Asam; K. L. Ray; G. L. Glish Collision-induced Signal Enhancement (CISE): A Method to Increase Product Ion Intensities in MS/MS and MSn Experiments, Anal. Chem., 70, 1831-1837 (1998).

M. J. Hostetler; J. E. Wingate; C. J. Zhong; J. E. Harris; R. W. Vachet; M. R. Clark; J. D. Londono; S. J. Green; J. J. Stokes; G. D. Wignall; G. L. Glish; M. D. Porter; N. D. Evans; R. W. Murray Alkanethiolate Gold Cluster Molecules with Core Diameters from 1.5 to 5.2 nm: Core and Monolayer Properties as a Function of Core Size, Langmuir, 14, 17-30 (1998).

R. W. Vachet; G. L. Glish New Method to Study the Effects of Peptide Sequence on the Dissociation Energetics of Peptide Ions, J. Amer. Soc. Mass Spectrom., 9, 175-177 (1998).

R. W. Vachet; K. L. Ray; G. L. Glish The Origin of Product Ions in the MS/MS Spectra of Peptides in a Quadrupole Ion Trap, J. Amer. Soc. Mass Spectrom., 9, 341-344 (1998).

R. W. Vachet; G. L. Glish Boundary-Activated Dissociation of Peptide Ions in a Quadrupole Ion Trap, Anal. Chem., 70, 340-346 (1998).

J. D. Lennon, III; G. L. Glish A MALDI Probe for Mass Spectrometers, Anal. Chem., 69, 2525-2529 (1997).

M. R. Asam; G. L. Glish Tandem Mass Spectrometry of Alkali Cationized Polysaccharides in a Quadrupole Ion Trap, J. Amer. Soc. Mass Spectrom., 8, 987 (1997).

R. W. Vachet; B. M. Bishop; B. W. Erickson; G. L. Glish Novel Peptide Dissociation: Gas Phase Intramolecular Rearrangement of Internal Amino Acid Residues, J. Am. Chem. Soc., 119, 5481-5488, (1997).

R. W. Vachet; G. L. Glish The Effect of Heavy Gases on the MS/MS Spectra of Peptides in the Quadrupole Ion Trap, J. Amer. Soc. Mass Spectrom., 7, 1194-1202, (1996).

T. Lin; M. R. Asam; G. L. Glish The Dissociation of Dimethylpyrroles: Evidence for Reaction from Isomeric Parent Ions J. Amer. Soc. Mass Spectrom., 7, 930-937 (1996).

R. W. Vachet; M. R. Asam; G. L. Glish Secondary Interaction Affecting the Dissociation Patterns of Arginine Containing Peptide Ions, J. Am. Chem. Soc., 118, 6252-6256 (1996).

Y. A. Ranasinghe; G. L. Glish Reactions of Phenylium Cations with Small Oxygen- and Nitrogen-Containing Molecules, J. Amer. Soc. Mass Spectrom., 7, 473-481 (1996).

J. D. Lennon, III; R. W. Vachet; D. Shinn; G. L. Glish Strategy for Pulsed Ionization on a Sector Mass Spectrometer, Anal. Chem., 68, 845-849 (1996).

R. W. Vachet; A. D.Winders; G. L. Glish Correlation of Kinetic Energy Loss in High Energy Collision-Induced Dissociation with Observed Peptide Product Ions, Anal. Chem., 68, 522-526 (1996).

M. J. Charles; S. A. McLuckey; G. L. Glish Competition Between Resonant Ejection and Ion Dissociation During Resonant Excitation in a Quadrupole Ion Trap, J. Amer. Soc. Mass Spectrom., 5, 1031-1041 (1994).

S. A. McLuckey; G. J. Van Berkel; D. E. Goeringer; G. L. Glish Ion Trap Mass Spectrometry Using High Pressure Ionization, Anal. Chem., 66, 737A-743A (1994).

S. A. McLuckey; G. J. Van Berkel; D. E. Goeringer; G. L. Glish Ion Trap Mass Spectrometry of Externally Generated Ions, Anal. Chem., 66, 689A-696A (1994).

G. L. Glish Multiple Stage Mass Spectrometry: The Next Generation Tandem Mass Spectrometry Experiment, Analyst, 119, 533-537 (1994).

J. Xu; L. D. Hulett, Jr.; T. A. Lewis; D. L. Donohue; S. A. McLuckey; G. L. Glish Positron Induced Dissociation of Organic Molecules, Phys. Rev. A, 47, 1023-1030 (1993).

D. M. Chambers; S. A. McLuckey; G. L. Glish Role of Gas Dynamics in Negative Ion Formation in an Atmospheric Sampling Glow Discharge Ionization Source, Anal. Chem., 65, 778-783 (1993).

D. M. Chambers; D. E. Goeringer; S. A. McLuckey; G. L. Glish Matrix-Assisted Laser Desorption of Biological Molecules in the Quadrupole Ion Trap Mass Spectrometer, Anal. Chem., 65, 14-20 (1993).

K. J. Hart; S. A. McLuckey; G. L. Glish Evidence of Isomerization During Ion Isolation in the Quadrupole Ion Trap, J. Amer. Soc. Mass Spectrom., 3, 680-682 (1992).

S. A. McLuckey; G. L. Glish; D. C. Duckworth; R. K. Marcus Radio-frequency Glow Discharge/Ion Trap Mass Spectrometry, Anal. Chem., 64, 1606-1609 (1992).

G. J. Van Berkel; S. A. McLuckey; G. L. Glish Electrochemical Origin of Radical Cations Observed in Electrospray Ionization Mass Spectra, Anal. Chem., 64, 1586-1593 (1992).

S. A. McLuckey; D. E. Goeringer; G. L. Glish Collisional Activation with Random Noise in Ion Trap Mass Spectrometry, Anal. Chem., 64, 1455-1460 (1992).

R. S. Ramsey; G. J. Van Berkel; S. A. McLuckey; G. L. Glish Determination of Pyrimidine Cyclobutane Dimers by Electrospray Ionization/Ion Trap Mass Spectrometry, Biomed. Mass Spectrom., 21, 347-352 (1992).

D. E. Goeringer; W. B. Whitten; J. M. Ramsey; S. A. McLuckey; G. L. Glish Theory of High Resolution Mass Spectrometry Achieved via Resonance Ejection in the Quadrupole Ion Trap, Anal. Chem, 64, 1434-1439 (1992).

K. J. Hart; S. A. McLuckey; G. L. Glish Reaction of Analyte Ions with Neutral Chemical Ionization Gas, J. Amer. Soc. Mass Spectrom., 549-557 (1992).

G. J. Van Berkel; S. A. McLuckey; G. L. Glish Unimolecular and Collision-Induced Reactions of Doubly Charged Porphyrins, J. Amer. Soc. Mass Spectrom., 235-242 (1992).

S. A. McLuckey; G. J. Van Berkel; G. L. Glish Mass Spectrometry/Mass Spectrometry of Small, Multiply Charged Oligonuceotides, n=4-8, J. Amer. Soc. Mass Spectrom., 3 60-70 (1992).

K.B. Jacobson; H.F. Arlinghaus; M.V. Buchanan; C.H. Chen; G.L. Glish; R.L. Hettich; S.A. McLuckey Applications of Mass Spectrometry to DNA Sequencing , Genetic Anal. Tech. Appl., 8, 223-229 (1991).

S.A. McLuckey; G.L. Glish; K.G. Asano; J.E. Bartmess Protonated Water and Protonated Methanol Cluster Decompositions in a Quadrupole Ion Trap, Int. J. Mass Spectrom. Ion Processes, 109, 171-186 (1991).

G.J. Van Berkel;S.A. McLuckey; G.L. Glish Preforming Ions in Solution via Charge-Transfer Complexation for Analysis by Electrospray Ionization Mass Spectrometry, Anal. Chem., 63, 2064-2068 (1991).

S.A. McLucke;, G.L. Glish; G.J. Van Berkel Charge Determination of Product Ions Formed from Collision-Induced Dissociation of Multiply Protonated Molecules via Ion/Molecule Reactions, Anal. Chem., 63, 1971-1978 (1991).

D.E. Goeringer; G.L. Glish; S.A. McLuckey Fixed-Wavelength Laser Ionization/Tandem Mass Spectrometry for Mixture Analysis in the Quadrupole Ion Trap, Anal. Chem., 63, 1186-1192 (1991).

G.J. Van Berkel; S.A. McLuckey; G.L. Glish Electrospray Ionization of Porphyrins Using a Quadrupole Ion Trap for Mass Analysis, Anal. Chem., 63, 1098-1109 (1991).

R.G. Cooks; G.L. Glish; S.A. McLuckey; R.E. Kaiser Ion Trap Mass Spectrometry, Chem. Eng. News, 69(12), 26-41 (1991).

S.A. McLuckey; G.J. Van Berkel; G.L. Glish; E.C. Wang; J.D. Henion Ion Spray Liquid Chromatography/Ion Trap Mass Spectrometry Determination of Biomolecules, Anal. Chem., 63, 375-383 (1991).

B.A. Eckenrode; S.A. McLuckey; G.L. Glish Comparison of Electron Ionization and Chemical Ionization Sensitivities on an Ion Trap Mass Spectrometer, Int. J. Mass Spectrom. Ion Processes, 106, 137-157 (1991).

S.A. McLuckey; G.L. Glish; G.J. Van Berkel Multiple Stages of Mass Spectrometry in a Quadrupole Ion Trap Mass Spectrometer: Prerequisites, Int. J. Mass Spectrom. Ion Processes, 106, 213-235 (1991).

S.A. McLuckey; D.E. Goeringer; G.L. Glish Selective Ion Isolation/Rejection Over a Broad Mass Range in the Quadrupole Ion Trap, J. Am. Soc. Mass Spectrom., 2, 11-21 (1991).

G.L. Glish, D.L. Donohue, S.A. McLuckey, B.A. Eckenrode, L.D. Hulett, Jr., Positron Ionization Mass Spectrometry: An Organic Mass Spectrometrist's View, Positron and Positronium Chemistry, Y.C. Jean, Ed., World Scientific, Singapore, pp 158-179, 1990.

G.J. Van Berkel, G.L. Glish, S.A. McLuckey, A.A. Tuinman, High-Pressure Ammonia Chemical Ionization Mass Spectrometry and Mass Spectrometry/Mass Spectrometry for Porphyrin Structure Determination, Energy and Fuels,4, 720-729 (1990).

K.G. Asano, S.A. McLuckey, G.L. Glish, Comparison of Atmospheric Sampling Glow Discharge Ionization with Electron Ionization, Spectroscopy Int. J., 8, 191-210 (1990).

B.A. Eckenrode, G.L. Glish, S.A. McLuckey, Negative Ion Chemical Ionization in a Quadrupole Ion Trap Using Reagent Anions Injected from an External Ion Source, Int. J. Mass Spectrom. Ion Processes,99, 151-167 (1990).

S.A. McLuckey, G.J. Van Berkel, G.L. Glish, Ion/Molecule Reactions of High Mass, Multiply Charged Peptides: Reactions of Dimethylamine with Ionized Cytochrome C, J. Am. Chem. Soc.,112, 5668-5670 (1990).

G.J. Van Berkel, G.L. Glish, S.A. McLuckey, Electrospray Ionization Combined with Ion Trap Mass Spectrometry, Anal. Chem., 62, 1284-1295 (1990).

D.L. Donohue, L.D. Hulett, Jr., S.A. McLuckey, B.A. Eckenrode, G.L. Glish, Positron Ionization III: Ionization of Organic Molecules by Positronium Formation, Chem. Phys. Lett., 168, 37-40 (1990).

R.A. Flurer, G.L. Glish,, S.A. McLuckey, Structures of NO3- formed Via Glow Discharge in Atmospheric Gases, J. Am. Soc. Mass Spectrom., 1, 217-224 (1990).

S.A. McLuckey, G.L. Glish, D.L. Donohue, L. D. Hulett, Jr., Positron Ionization Mass Spectrometry II: Ionization by Fast Positrons, Int. J. Mass Spectrom. Ion Processes, 97, 237- 252 (1990).

D.L. Donohue, L.D. Hulett, Jr., S.A. McLuckey, G.L. Glish,, H.S. McKown, Positron Ionization Mass Spectrometry I: Instrumentation, Int. J. Mass Spectrom. Ion Processes, 97, 227- 236 (1990).

J.N. Louris, J.S. Brodbelt-Lustig, R.G. Cooks, G.L. Glish, G.J. Van Berkel,, S.A. McLuckey, Ion Isolation and Sequential Stages of Mass Spectrometry in a Quadrupole Ion Trap Mass Spectrometer, Int. J. Mass Spectrom. Ion Processes, 96, 117-137 (1990).

G.J. Van Berkel, G.L. Glish, S.A. McLuckey, A.A. Tuinman, Porphyrin Pyrrole Sequencing: Low Energy Collision-Induced Dissociation of (M+7H)+ Generated In-Situ During Ammonia Chemical Ionization, Anal. Chem., 62, 786-793 (1990).

G.L. Glish, S.A. McLuckey,, K.G. Asano, Determination of Daughter Ion Formulas via Multiple Stages of Mass Spectrometry, J. Am. Soc. Mass Spectrom., 1, 166-173 (1990).

S.A. McLuckey, G.L. Glish, B.C. Grant, The Simultaneous Monitoring for Parent Ions of a Specified Daughter Ion: A Method for Rapid Screening Applications, Anal. Chem., 62, 56-61 (1990).

G.L. Glish, D.E. Goeringer, K.G. Asano, S.A. McLuckey, Laser Desorption Mass Spectrometry and MS/MS with a Three Dimensional Quadrupole Ion Trap, Int. J. Mass Spectrom. Ion Processes, 94, 15-24 (1989).

G.J. Van Berkel, G.L. Glish, S.A. McLuckey, A.A. Tuinman, Mechanism of Porphyrin Reduction and Decomposition in a High Pressure Chemical Ionization Plasma, J. Am. Chem. Soc., 111, 6027-6035 (1989).

S.A. McLuckey, G.L. Glish, K.G. Asano, The Coupling of an Atmospheric Sampling Ion Source with an Ion Trap Mass Spectrometer, Anal. Chim. Acta, 225, 25-35 (1989).

G.L. Glish, S.A. McLuckey, Scan Modes for Hybrid Mass Spectrometers, Org. Mass Spectrom., 24, 470-478 (1989).

G.J. Van Berkel, G.L. Glish, S.A. McLuckey, Geoporphyrin Structure Determination Using Chemical Ionization Mass Spectrometry/Mass Spectrometry, Org. Geochem., 14, 203-212 (1989).

S.A. McLuckey, K.G. Asano, G.L. Glish, Self Chemical Ionization in an Ion Trap Mass Spectrometer, Anal. Chem. 60, 2312-2314 (1988).

S.A. McLuckey, G.L. Glish, K.G. Asano, B.C. Grant, Atmospheric Sampling Glow Discharge Ionization Source for the Analysis of Trace Organics in Ambient Air, Anal. Chem. 60, 2220-2227 (1988).

M.V. Buchanan, I.B. Rubin, M.S. Wise, G.L. Glish, Formation of [M+14] Anions from Fluorene: Negative Ion CI Studies Using GC/MS, MS/MS and FTMS, Biomed. Environ. Mass Spectrom., 14, 395-399 (1987).

S.A. McLuckey, G.L. Glish, Dished Peaks from Collision-Induced Dissociations of Nitroaromatic Anions,Int. J. Mass Spectrom. Ion Phys., 76, 41-46 (1987).

S.A. McLuckey, G.L. Glish, P.E. Kelley, Collision-Activated Dissociation of Negative Ions in an Ion Trap Mass Spectrometer, Anal. Chem., 59, 1670-1674 (1987).

S.A. McLuckey, G.L. Glish, The Effect of Charge on Hydroxyl Loss from Ortho-substituted Nitrobenzene Ions, Org. Mass Spectrom., 22, 224-228 (1987).

G.L. Glish, S.A. McLuckey, H.S. McKown, Improved Performance of a Tandem Quadrupole/Time-of-Flight Mass Spectrometer, Anal. Instrum., 16, 191-206 (1987).

G.L. Glish, S.A. McLuckey, E.H. McBay, L.K. Bertram, Design and Performance of a Hybrid Mass Spectrometer of QEB Geometry, Int. J. Mass Spectrom. Ion Phys., 70, 321-338 (1986).

G.L. Glish, S.A. McLuckey, High-Resolution Detection of Daughter Ions with a Hybrid Mass Spectrometer, Anal. Chem., 58, 1887-1889 (1986).

G.L. Glish, S.A. McLuckey, Hybrid Instruments for Mass Spectrometry/Mass Spectrometry, Anal. Instrum., 15, 1-36 (1986).

A.J. Brown, G.L. Glish, E.H. McBay, F. Snyder, Alkyldihydroxyacetonephosphate Synthase Mechanism: 18O Studies of Fatty Acid Release from Acyldihydroxyacetone Phosphate, Biochem., 24, 8012-8016 (1985).

S.A. McLuckey, G.L. Glish, J.A. Carter, The Analysis of Explosives by Tandem Mass Spectrometry, J. Forens. Sci., 30, 773-788 (1985).

P.J. Todd, G.L. Glish, W.H. Christie, A Molecular Secondary Ionization Source for Use with a High Performance Tandem Mass Spectrometer, Int. J. Mass Spectrom. Ion Phys., 61, 215-230 (1984).

G.L. Glish, D.E. Goeringer, Tandem Quadrupole/Time-of-Flight Instrument for Mass Spectrome- try/Mass Spectrometry, Anal. Chem., 56, 2291-2295 (1984).

G.L. Glish, P.J. Todd, K.L. Busch, R.G. Cooks, MS/MS Spectra of Organic Ions Generated by Secondary Ion Mass Spectrometry, Int. J. Mass Spectrom. Ion Phys., 56, 177-192 (1984).

K.L. Busch, G.L. Glish, New Biological Dimensions in Mass Spectrometry, BioTechniques, 2, 128-137 (1984).

G.L. Glish, E.H. McBay, M.M. Goodman, F.F. Knapp, Jr., The Fragmentation of Chalcogen Containing Fatty Acids and Their Methyl Esters, Biomed. Mass Spectrom., 10, 572-576 (1983).

R.G. Cooks, K.L. Busch, G.L. Glish, Mass Spectrometry: Analytical Capabilities and Potentials, Science, 222, 273-281 (1983).

G.L. Glish, D.H. Smith, Thermal Ionization of Quaternary Ammonium Salts, Int. J. Mass Spectrom. Ion Phys., 50, 143-149 (1983).

G.L. Glish, S.A. McLuckey, T.Y. Ridley, R.G. Cooks, A New Hybrid Sector/Quadrupole Mass Spectrometer for Mass Spectrometry/Mass Spectrometry, Int. J. Mass Spectrom. Ion Phys., 41, 157-177 (1982).

R.V. Gentry, G.L. Glish, E.H. McBay, Differential Helium Retention in Zircons: Implications of Nuclear Waste Containment, Geophys. Res. Lett., 9, 1129-1130 (1982).

G.L. Glish, P.J. Todd, Collision Region for Mass Spectrometry/Mass Spectrometry, Anal. Chem., 54, 842-843 (1982).

S.A. McLuckey, G.L. Glish, R.G. Cooks, Kinetic Energy Effects in Mass Spectrometry/Mass Spectrometry Using a Sector/Quadrupole Tandem Instrument, Int. J. Mass Spectrom. Ion Phys., 39, 219-230 (1981).

R.G. Cooks, G.L. Glish, Mass Spectrometry/Mass Spectrometry, Chem. Eng. News, 59, 40-52 (1981).

D.J. Burinsky, G.L. Glish, R.G. Cooks, J.J. Zwinselman, N.N.M Nibbering, Unimolecular Dissociations at Short Times. A Comparison of Angle-Resolved Mass Spectrometry and Field Ionization Kinetics, J. Am. Chem. Soc., 103, 465-467 (1981).

G.L. Glish, R.G. Cooks, Direct Mixture Analysis by Double Quadrupole Mass Spectrometry, Anal. Chim. Acta, 119, 145-148 (1980).

G.L. Glish, P.H. Hemberger, R.G. Cooks, Ion Structure Determinations and Ion-Molecule Reactions by Double Quadrupole Mass Spectrometry, Anal. Chim. Acta, 119, 137-144 (1980).

A. Maquestiau, R.Flammang, G.L. Glish, J.A. Laramee, R.G. Cooks, Kinetic Energy Release and Ion Structure: (C6H6O+.), Org. Mass Spectrom., 15, 131-133 (1980).

G.L. Glish, V.M. Shaddock, K. Harmon, R.G. Cooks, Rapid Analysis of Complex Mixtures by Mass Spectrometry/Mass Spectrometry, Anal. Chem., 52, 165-167 (1980).

G.L. Glish, R.G. Cooks, The Fischer Indole Synthesis and Pinacol Rearrangement in the Mass Spectrometer, J. Am. Chem. Soc., 100 6720,6725 (1978).

Abstracts

The basics of mass spectrometry in the twenty-first century

Gary L. Glish, and Richard Vachet

Enormous advances in our understanding of the chem. underlying life processes have identified new targets for therapeutic agents. The discovery of effective therapeutics to address these targets is often accomplished through parallel synthetic and screening efforts. In almost all cases, what has enabled target identification and allowed parallel approaches to drug discovery to be effective are the development of either new anal. tools or the improvement of currently existing ones. Among these tools, mass spectrometry has evolved to become an irreplaceable technique in the anal. of biol. related mols. This article will guide researchers in drug discovery through the basic principles of mass spectrometry.

Matrix-assisted laser desorption/ionization-boundary-activated dissociation of peptide ions in a quadrupole ion trap,

Ray, Kenneth L.; Glish, Gary L.

The nonresonant excitation technique of boundary-activated dissocn. (BAD) has been used to obtain tandem mass (MS/MS) spectra for peptide ions generated by matrix-assisted laser desorption/ionization (MALDI) in a quadrupole ion trap. BAD MS/MS spectra for proctolin, des-Arg9-bradykinin, and substance P are qual. similar to those for which resonant excitation has been used and can be obtained with the same activation time. The conditions for optimal product ion formation are easily established when BAD is used because of its dependence upon a single activation parameter. Consequently, MS/MS spectra of MALDI-generated ions are easier to obtain than when single-frequency resonant excitation is used. These advantages, in conjunction with the simpler electronic equipment required for the implementation of BAD, provide an alternative to broadband excitation when MS/MS data for MALDI-generated ions are desired.

Pseudo-MS3 in a MALDI orthogonal quadrupole-time of flight mass spectrometer

Raska, Christina S.; Parker, Carol E.; Huang, Cai; Han, Jun; Glish, Gary L.; Pope, Marshall; Borchers, Christoph H.

Both the matrix selected and the laser fluence play important roles in MALDI-quadrupole/time of flight (QqTOF) fragmentation processes. "Hot" matrixes, such as -cyano-4-hydroxycinnamic acid (HCCA), can increase fragmentation in MS spectra. Higher laser fluence also increases fragmentation. Typical peptide fragment ions obsd. in the QqTOF are a, b, and y ion series, which resemble low-energy CID product ions. This fragmentation may occur in the high-pressure region before the first mass-analyzing quadrupole. Fragment ions can be selected by the first quadrupole (Q1), and further sequenced by conventional MS/MS. This allows pseudo-MS3 expts. to be performed. For peptides of higher mol. wt., pseudo-MS3 can extend the mass range beyond what is usually accessible for sequencing, by allowing one to sequence a fragment ion of lower mol. wt. instead of the full-length peptide. Peptides that predominantly show a single product ion after MS/MS yield improved sequence information when this technique is applied. This method was applied to the anal. of an in vitro phosphorylated peptide, where the intact enzymically-generated peptide showed poor dissocn. via MS/MS. Sequencing a fragment ion from the phosphopeptide enabled the phosphorylation site to be unambiguously detd.

Hydrogen Abstraction and Decomposition of Bromopicrin and Other Trihalogenated Disinfection Byproducts by GC/MS.

Chen, Paul H.; Richardson, Susan D.; Krasner, Stuart W.; Majetich, George; Glish, Gary L..

Tribromonitromethane (bromopicrin), dibromochloronitromethane, bromodichloronitromethane, and trichloronitromethane (chloropicrin) have been identified as drinking water disinfection byproducts (DBP). These compds. are thermally unstable and decomp. under commonly used injection port temps. (200-250 ) during gas chromatog. (GC) or GC/mass spectrometry (GC/MS) anal. Major decompn. products are haloforms (e.g., bromoform), which result from the abstraction of a H atom from the solvent by thermally-generated trihalomethyl radicals. Several other products formed by radical reactions with the solvent and other radicals were also detected. Trihalonitromethanes also decomp. in hot GC/MS transfer lines; mass spectra obtained were mixed spectra of un-decompd. parent compds. and decompn. products. This can complicate the GC/MS identification of these compds. Trihalomethyl compds. which do not have a nitro group, e.g., tribromoacetonitrile, carbon tetrabromide, Me tribromoacetate, and tribromoacetaldehyde, do not decomp. or only slightly decomp. in GC injection ports and GC/MS transfer lines. Studied brominated trihalomethyl compds. also showed H/Br exchange by some of their fragment ions. This H/Br exchange also makes identification of these compds. in drinking water more difficult. The extent of H/Br exchange depended on the mass spectrometer ion source temp.; it is proposed the internal surface of the ion source is involved in this process.

Direct MALDI-MS/MS of phosphopeptides affinity-bound to immobilized metal ion affinity chromatography beads

Raska, Christina S.; Parker, Carol E.; Dominski, Zbigniew; Marzluff, William F.; Glish, Gary L.; Pope, R. Marshall; Borchers, Christoph H.

Immobilized metal ion affinity chromatog. (IMAC) is a useful method to selectively isolate and enrich phosphopeptides from a peptide mixt. Mass spectrometry is a very suitable method for exact mol. wt. detn. of IMAC-isolated phosphopeptides, due to its inherent high sensitivity. Even exact mol. wt. detn., however, is not sufficient for identification of the phosphorylation site if more than one potential phosphorylation site is present on a peptide. The previous method of choice for sequencing the affinity-bound peptides was electrospray tandem mass spectrometry (ESI-MS/MS). This method required elution and salt removal prior to MS anal. of the peptides, which can lead to sample loss. Using a matrix-assisted laser desorption/ionization (MALDI) source coupled to an orthogonal injection quadrupole time-of-flight (QqTOF) mass spectrometer with true MS/MS capabilities, direct sequencing of IMAC-enriched peptides has been performed on IMAC beads applied directly to the MALDI target. The utility of this new method has been demonstrated on a protein with unknown phosphorylation sites, where direct MALDI-MS/MS of the tryptic peptides bound to the IMAC beads resulted in the identification of two novel phosphopeptides. Using this technique, the phosphorylation site detn. is unambiguous, even with a peptide contg. four potentially phosphorylated residues. Direct anal. of phosphorylated peptides on IMAC beads does not adversely affect the high-mass accuracy of an orthogonal injection QqTOF mass spectrometer, making it a suitable technique for phosphoproteomics.

Collision-induced signal enhancement (CISE): the use of boundary activation to effect non-resonant CISE

Asam, Michael R.; Glish, Gary L..

An alternative to resonant excitation collision-induced signal enhancement (CISE) is presented. This alternative uses boundary activation instead of resonant excitation to effect CISE and is called boundary-activated CISE (BA-CISE). There are 3 ways to effect BA-CISE to enhance the signal for an MSn+1 expt. Each technique uses the z = 0 boundary, which ions encounter from high to low mass/charge ratio. BA-CISE produces an almost 900% increase in the C2 ion of [maltohexaose + Li]+. The use of a heavy collision gas in addn. to the He bath gas generally produced a signal enhancement inferior to the same expt. without the heavy gas.

Charge permutation reactions in beam type mass spectrometers

Danell, Allison S.; Glish, Gary L.

A review of the gas-phase reactions, in beam type mass spectrometers, that change the charge states of ions. The Cooks research group was a leader in both the understanding and use of these charge-changing reactions. The charge of ions can be manipulated in beam type instruments via collisions with neutral gas atoms or mols. in the high ion kinetic energy regime. The two major processes, charge inversion and charge stripping due to high energy ion/neutral collisions, are discussed. Charge permutation reactions often gave unique ion structures that aid in the differentiation of isomers. The products of charge permutation reactions may possess excess internal energy that cause the ions to fragment, and these fragment ions may provide complementary information to that obtained from high energy collision-induced dissocn. The charge of ions also can be changed as a result of a collision with a surface in the low ion kinetic energy regime. Charge exchange and charge inversion processes that occur as a result of low energy ion/surface collisions are presented.

Evidence for ionization-related conformational differences of peptide ions in a quadrupole ion trap

Allison S. Danell and Gary L. Glish

The differences in boundary-activated dissociation (BAD) onsets have been investigated for peptide ions that were generated by two different ionization techniques, nanoflow electrospray ionization (nanoESI) and liquid secondary-ion mass spectrometry (LSIMS). BAD onsets of these ions were determined to compare the relative internal energies of the ions. Protonated peptide ions formed by nanoESI had lower BAD onsets than ions formed by LSIMS. The BAD onsets of peptides derivatized to have a fixed charge on the N-terminus also were lower for those generated by nanoESI than those generated by LSIMS. The BAD onsets of ions formed by nanoESI did not change with the variation of collisional cooling periods after gating ions into the ion trap and after isolating them prior to dissociation, indicating that the ions formed by the two ionization techniques would not adopt the same energy distributions. It is proposed that the ions formed by the two techniques differ in secondary structure, and the LSIMS ions are collisionally cooled to a lower local minimum along the potential energy surface than the nanoESI ions. Ions formed by both techniques show the same dissociation patterns, so assuming the absolute energy required for dissociation is the same, the LSIMS ions possess a higher critical energy of dissociation. This leads to the observation of the higher BAD onset. (JASMS, 13, 1331)

Thermally Assisted Infrared Multiphoton Photodissociation

Anne H. Payne and Gary L. Glish

Thermally assisted infrared multiphoton photodissociation (TA-IRMPD) provides an effective means to dissociate ions in the quadrupole ion trap mass spectrometer (QITMS) without detrimentally affecting the performance of the instrument. IRMPD can offer advantages over collision-induced dissociation (CID). However, collisions with the QITMS bath gas at the standard pressure and ambient temperature cause IR-irradiated ions to lose energy faster than photons can be absorbed to induce dissociation. The low pressure required for IRMPD (10^-5 Torr) is not that required for optimal performance of the QITMS (10^-3 Torr), and sensitivity and resolution suffer. TA-IRMPD is performed with the bath gas at an elevated temperature. The higher temperature of the bath gas results in less energy lost in collisions of the IR-excited ions with the bath gas. Thermal assistance allows IRMPD to be used at or near optimal pressures, which results in an ~1 order of magnitude increase in signal intensity. Unlike CID, IRMPD allows small product ions, those less than about one-third the m/z of the parent ion, to be observed. IRMPD should also be more easily paired with fluctuating ion sources, as the corresponding fluctuations in resonant frequencies do not affect IRMPD. Finally, while IR irradiation nonselectively causes dissociation of all ions, TA-IRMPD can be made selective by using axial expansion to move ions away from the path of the laser beam. (Anal. Chem., 73, 3542.)

Dissociation Pathways of Alkali-Cationized Peptides: Opportunities for C-terminal Peptide Sequencing

Tong Lin, Anne H. Payne, and Gary L. Glish

Dissociation pathways of alkali-cationized peptides have been studied using multiple stages of mass spectrometry (MSx) with a quadrupole ion trap mass spectrometer. Over 100 peptide ions ranging from 2 to 10 residues in length and containing each of the 20 common amino acids have been examined. The formation of the [b_n-1 + Na + OH]⁺ product ion is the predominant dissociation pathway for the majority of the common amino acids. This product corresponds to a sodium-cationized peptide one residue shorter in length than the original peptide. In a few cases, product ions such as [b_n-1 + Na - H]⁺ and those formed by loss, or partial loss, of a sidechain are observed. Both [b_n-1 + Na + OH]⁺ and [b_n-1 + Na - H]⁺ product ions can be selected as parent ions for a subsequent stage of tandem mass spectrometry (MS/MS). It is shown that these dissociation patterns provide opportunities for peptide sequencing by successive dissociation from the C-terminus of alkali-cationized peptides. Up to seven stages of MS/MS have been performed on a series of [b_n-1 + Na + OH]⁺ ions to provide sequence information from the C-terminus. This method is analogous to Edman degradation except that the cleavage occurs from the C-terminus instead of the N-terminus, making it more attractive for N-terminal blocked peptides. The isomers leucine and isoleucine cannot be differentiated by this method but the isobars lysine and glutamine can. (J. Am. Soc. Mass Spectrom., 12, 497.)

Gas-phase ion/ion interactions between peptides or proteins and iron ions in a quadrupole ion trap

Anne H. Payne and Gary L. Glish

The gas-phase ion/ion reactions of iron ions with oppositely charged peptide and protein ions were studied in a quadrupole ion trap. Both Fe⁺ and FeCO₂^- were investigated as possible reactant ions for gas-phase cleavage of peptide and protein ions. Several types of reaction products were observed. Charge exchange lowered the charge states of the proteins. Attachment resulted in a complex of the protein ion and the iron ion. In some cases bonds were broken in the protein ions, but it is unclear whether this is due to an insertion of the iron ion into a bond or due to the energetic reaction of oppositely charged species. Some preference was observed for bond cleavage near sulfur. Two disulfide bonds were broken in one case, and bonds adjacent to a cysteine residue were broken in another. (Int. J. Mass Spectrom., 204, 47.)

A new approach for effecting surface-induced dissociation in an ion cyclotron resonance mass spectrometer: a modeling study

Ryan M. Danell and Gary L. Glish

With the increasing use of ion cyclotron resonance (ICR) for tandem mass spectrometry (MS/MS) analysis of biomolecules, surface-induced dissociation (SID) should be given serious consideration as an ion activation technique. There are at least two compelling reasons to consider SID: it can deposit significant amounts of internal energy into large ions, and no collision gas is required. These potential advantages have led us to undertake a modeling study of the SID process in an ICR using the ion optics program SIMION. The various methods previously used to obtain SID spectra are compared to a new approach for effecting SID in an ICR. Through simulations, many different parameters present in the experiment are correlated to the kinetic energy of the parent ion upon impact and the overall product ion collection efficiency (and hence the signal intensity) expected. The modeling results suggest this new approach allows larger, more precise, and controllable impact energies to be used, as well as providing higher collection efficiencies. The validity of the modeling results is supported by good qualitative agreement with previously reported experimental results. (J. Am. Soc. Mass Spectrom., 11, 1107.)

Synthesis of derivatized amino acids for the study of electron transfer

Scafford A. Serron, W. Stephen Aldridge III, Ryan M. Danell and Thomas J. Meyer

The synthesis of a new electron transfer donor and two new ruthenium chromophores are described based on coupling to derivatized proline residues for the purpose of constructing molecular assemblies capable of undergoing photoinduced electron transfer. (Tetrahedron Lett., 41, 4039.)

C-terminal peptide sequencing using acetylated peptides with MSⁿ in a quadrupole ion trap

Anne H. Payne, J. Holly Chelf, and Gary L. Glish

MS/MS has been used to sequence peptides and small proteins for a number of years. This method allows one to isolate the peptide of interest, which makes it possible to analyze impure samples and unseparated mixtures, such as protein digests. Collision-induced dissociation (CID) of the selected peptide ion generates the product ions that provide sequence information. However, often the MS/MS spectrum does not provide adequate information for complete sequence determination. The quadrupole ion trap has the capability to do multiple stages of mass spectrometry, MSⁿ, which can increase the information available to determine the peptide sequence. A regular and predictable dissociation pattern for peptides further simplifies this analysis. By forming predominantly one type of ion, ambiguity is removed as to whether the ion is N- or C-terminal. This pattern can also be advantageous in that ion intensity remains concentrated for the next stage of MS/MS. In this work, a method to take advantage of the MSⁿ capabilities of the quadrupole ion trap by controlling the dissociation pathways is explored. Dissociation is altered by acetylating the N-terminus of the peptide. MSⁿ of a variety of acetylated peptides is used to determine the effects of the identity of the C-terminal residue and the length of the peptide on the dissociation pathways observed. (Analyst, 125, 635.)

Determination of the Dissociation Kinetics of a Transient Intermediate

Michael R. Asam and Gary L. Glish

Tandem mass spectrometry (MS/MS) provides information on the dissociation pathways of gas-phase ions by providing a link between product-ions and parent ions. However, there exists a distinct possibility that a parent ion does not dissociate directly to the observed product-ion, but that the reaction proceeds through unobserved reaction intermediates. This work describes the discovery and kinetic analysis of an unobserved reaction intermediate with a quadrupole ion trap. [a4 – NH3] ions formed from [YG bFL + H] ions dissociate to [(F*YG – NH3) - CO] ions. It is expected, however, from previous results, that [F*YG – NH3] ions should form prior to [(F*YG – NH3) - CO] ions. Double-resonance experiments are used to demonstrate the existence of intermediat e [F*YG – NH3] ions. Various kinetic analyses are then performed using traditional CID kinetics and double-resonance experiments. The phenomenological rates of formation and decay of peptide rearrangement ion dissociation products are determined by curv e fitting decay and formation data generated with the kinetics experiments. The data generated predict an observable level of the intermediate in a time frame accessible but previously not monitored. By examining early product-ion formation, the interme diate ions, [F*YG - NH3]+, are observed. (J. Am. Soc. Mass Spectrom., 10, 119.)

C-Terminal Peptide Sequencing via Multistage Mass Spectrometry

Tong Lin and Gary L. Glish

Results are presented showing the ability to obtain C-terminal sequence information from peptides by multiple stages of mass spectrometry. Under typical low-energy collision-induced dissociation conditions of quadrupole ion trap and ion cyclotron resonance mass spectrometers, lithium- and sodium-cationized peptides dissociate predominantly by reaction at the C-terminal peptide bond or an adjacent bond. For the majority of cases studied, the dominant reaction is a rearrangement process that results in the loss of the C-terminal residue and formation of a product ion that is one amino acid shorter than the original peptide ion. Using the multistage MS/MS capabilities of quadrupole ion trap and ion cyclotron resonance mass spectrometers, a subsequent stage of MS/MS can be performed to determine the identity of the new C-terminal residue. Up to eight stages of MS/MS have been performed with both quadrupole ion trap and ion cyclotron resonance mass spectrometers. In general, the same dissociation pathways are observed with both instruments, although occasionally there are significant differences in the branching ratios of competing pathways. (Anal. Chem., 70, 5162.)

Collision-induced Signal Enhancement (CISE): A Method to Increase Product Ion Intensities in MS/MS and MSn Experiments

Michael R. Asam, Kenneth L. Ray, and Gary L. Glish

Collision-induced Signal Enhancement (CISE), a new technique to enhance the MSn capabilities of the quadrupole ion trap, is demonstrated. CISE is based on the chemistry, i.e., the dissociation pathways, of the analyte examined. Polysaccharides up to he xamers are used to demonstrate the capabilities of CISE to enhance signal in two distinct functional modes. Mode 1 CISE is designed to enhance the signal of an ion desired for MSn analysis. Mode 2 CISE is designed to enhance structurally significant pro duct ions in an MS/MS spectrum. Two different approaches can be utilized to effect the two functional modes of CISE. Both approaches use conventional resonant excitation techniques to effect dissociation, which is performed non-analytically, i.e., witho ut isolation of the ions to be dissociated. The two approaches are 1) single frequency resonance excitation, and 2) broadband waveform resonant excitation. Experimental results for Mode 1 CISE analysis demonstrate up to a 17.3 fold signal increase for the single frequency approach and 5.3 fold using broadband excitation. Mode 2 CISE analysis shows up to a 16.3 fold increase in signal strength with single frequency excitation and 3.3 fold using broadband excitation. (Anal. Chem., 70, 183 1.)

Alkanethiolate Gold Cluster Molecules with Core Diameters from 1.5 to 5.2 nm: Core and Monolayer Properties as a Function of Core Size

Michael J. Hostetler, Julie E. Wingate, Chuan-Jian Zhong, Jay E. Harris, Richard W. Vachet, Michael R. Clark, J. David Londono, Stephen J. Green, Jennifer J. Stokes, George D. Wignall, Gary L. Glish, Marc D. Porter, Neal D. Evans, and Royce W. Murray

The mean size of the gold (Au) core in the synthesis of dodecanethiolate-stabilized Au cluster compounds can be finely adjusted by choice of the Au:dodecanethiolate ratio and the temperature and rate at which the reduction is conducted. The Au clusters have been examined with a large number of independent analytical tools, producing a remarkably consistent picture of these materials. Average cluster and core dimensions, as ascertained by 1H NMR line broadening, high-resolution transmission electron microscopy, small-angle X-ray scattering, and thermogravimetric analysis, vary between diameters of 1.5 and 5.2 nm (~110-4800 Au atoms/core). The electronic properties of the Au core were examined by UV/vis and X-ray photoelectron spectroscopy; the core appears to remain largely metallic in nature even at the smallest core sizes examined. The alkanethiolate monolayer stabilizing the Au core ranges with core size from ~53 to nearly 520 ligands/core, and was probed by Fourier transform infrared spectroscopy, differential scanning calorimetry, contact-angle measurements, and thermal desorption mass spectrometry. The dodecanethiolate monolayer on small and large core clusters exhibits discernable differences; the line dividing "3-dimensional" monolayers and those resembling self-assembled monolayers on flat Au (2-dimensional monolayers) occurs at clusters with ~4.4 nm core diameters. (Langmuir, 14, 17.)

New Method to Study the Effects of Peptide Sequence on the Dissociation Energetics of Peptide Ions

Richard W. Vachet and Gary L. Glish

A new method using a quadrupole ion trap mass spectrometer has been developed to study the dissociation patterns of singly-protonated peptides. The new approach involves using boundary-activated dissociation (BAD) to characterize the ease of dissociation of peptide ions. Insight can be gained into the effect of specific peptide sequences on the dissociation energetics of protonated peptides. Increased knowledge of the effects of specific sequences on the dissociation patterns of peptide ions should improve the ability to interpret complex tandem mass spectrometric (MS/MS) spectra. This method has confirmed the previously observed increase in the energy needed for the dissociation of peptide ions containing basic residues. In addition, this technique has revealed the effect of the location of proline residues on the dissociation energetics of peptides with this amino acid. (J. Am. Soc. Mass Spectrom., 9, 175.)

The Origin of Product Ions in the MS/MS Spectra of Peptides in a Quadrupole Ion Trap

Richard W. Vachet, Kenneth L. Ray, and Gary L. Glish

Stored waveform inverse Fourier transform (SWIFT) and double resonance techniques have been used in conjunction with a quadrupole ion trap to study the dissociation patterns of peptide ions. These experiments provide insight into the origin of individua l product ions in an MS/MS spectrum. Results show for a series of leucine enkephalin analogues with five amino acid residues that the b4 ion is the main product ion through which many other product ions arise. It was also observed that the percentage of the a4 product ions that are formed directly from the protonated molecule (M+H)+ depends on the nature of the fourth amino acid residue. In addition, it was determined that in the peptides studied here lower series b ions (e.g. b3) arise from direct dis sociation of higher series b ions (e.g. b4) only about 50% of the time. (J. Am. Soc. Mass Spectrom., 9, 341.)

Boundary-Activated Dissociation of Peptide Ions in a Quadrupole Ion Trap

Richard W. Vachet and Gary L. Glish

Boundary-activated dissociation (BAD) of peptides has been investigated as an alternative to the use of resonant excitation to effect collision-induced dissociation (CID) in the quadrupole ion trap. BAD's non-resonant excitation mechanism overcomes a maj or drawback in resonant excitation, namely the variation of the resonant excitation frequency as a function of ion space charging. As with resonant excitation, the pulsed introduction of heavy gases (argon, xenon) extends the applicability of BAD when pe rforming tandem mass spectrometry (MS/MS) on peptide ions. The presence of heavy gases during ion activation allows greater internal energy deposition and also enables BAD to be performed at much lower trapping field strengths (lower qz values) than prev iously reported for this technique. This extends the mass range over which product ions can be collected. (Anal. Chem., 70, 340.)

A MALDI Probe for Mass Spectrometers

John D. Lennon, III and Gary L. Glish

A new MALDI probe has been designed that uses transmission geometry. This geometry allows the probe to be fashioned after typical EI/CI solids probes which enables it to be introduced into spatially constrained ion source regions such as encountered in q uadrupole ion trap mass spectrometers. In the probe design demonstrated here, light from a fiber optic irradiates the backside of a sample through a small piece of quartz on which the sample has been directly deposited. The performance characteristics e xhibited by utilizing this probe for MALDI on a quadrupole ion trap mass spectrometer are similar to those which can be obtained through the traditional methods of implementing MALDI. Spectra have been obtained from 50 femtomoles of total loading of Bomb esin, MS/MS has been performed on 5 picomoles of des-Arg9- Bradykinin, and the analyte ion signal is shown to last for over 2500 laser shots for 2 picomoles of Bombesin. Optical micrographs showing the crystal distribution of a sample containing 2 picomo les of Bombesin have been obtained as a function of the number of laser shots for a single sample loading. Although this probe was designed for use with the quadrupole ion trap, it can be adapted for use with all types of mass spectrometers. Thus, with only one laser, one fiber optic, and this probe, MALDI can be performed on multiple instruments in a lab. (Anal. Chem., 69, 2525.)

Tandem Mass Spectrometry of Alkali Cationized Polysaccharides in a Quadrupole Ion Trap

Michael R. Asam and Gary L. Glish

Quadrupole ion trap mass spectrometry is used to study the linkage type dependent dissociation pathways of alkali-cationized disaccharides, mostly of the type glucosyl(1 --> X)glucose (X = 1,2,3,4 or 6). The reaction mechanisms of a set of disaccharides containing all possible a anomeric linkage types and some b anomers are probed with tandem mass spectrometry, MSn, and double resonance experiments. Tandem mass spectrometry experiments on an 18O-labeled disaccharide show that the dissociation paths for Li and Na cationized species are the same. Experiments on three trisaccharides (isomaltotriose, maltotriose, and panose), a tetrasaccharide (isomaltotetraose) and a pentasaccharide (maltopentaose) show that tandem mass spectrometry provides all available linkage information and MSn can provide selected linkage information. The mode of alkali binding is examined via semi-empirical calculations and by measuring alkali-carbohydrate relative cation affinities. (J. Am. Soc. Mass Spectrom., 8, 987.)

Novel Peptide Dissociation: Gas Phase Intramolecular Rearrangement of Internal Amino Acid Residues

Richard W. Vachet, Barney M. Bishop, Bruce W. Erickson, and Gary L. Glish

Unique intramolecular rearrangement product ions have been observed in the product ion spectra of a number of peptides. Multiple stages of mass analysis (MSn), molecular modeling, and chemical modifications of peptides have been used to provide insight i nto the mechanism of this rearrangement reaction. The rearrangement process begins with a four residue immonium ion that transfers a proton from the immonium nitrogen to the primary amine on the N-terminus. The proton transfer leads to the rearrangement of the peptide, exposing an internal amino acid on the terminus of the new ion. The internal amino acid that becomes the terminus of the new ion is then readily lost. The reaction seems to be benefit from an extended experimental time frame available f or reaction. The reaction is most prominent in quadrupole ion trap and Fourier-transform ion cyclotron resonance experiments, is observed under some conditions in a triple quadrupole, but is not seen in a sector instrument. Without previous knowledge o f this process, the peptide sequence as determined by MS/MS could be misidentified. (J. Am. Chem. Soc., 119, 5481.)

Effects of Heavy Gases on the Tandem Mass Spectra of Peptide Ions in the Quadrupole Ion Trap

Richard W. Vachet and Gary L. Glish

Heavy gases (xenon, argon, krypton, methane) have been used to improve the performance of the quadrupole ion trap when performing collision-induced dissociation on peptides. MS/MS spectra reveal that increased amounts of internal energy can be deposited into peptide ions and more structural information can be obtained. Specifically, the pulsed introduction of the heavy gases (as reported previously be Doroshenko, V. M.; Cotter, R. J. Anal. Chem. 1996, 68, 463) provides greater energy deposition without the deleterious effects that static pressures of heavy gas have on spectra. Internal energy deposition as indicated by a qualitative evaluation of MS/MS spectra shows pulsed introduction of heavy gases enables ions to obtain more internal energy than pos sible by using static pressure of the same heavy gases. A linear correlation is observed between the percentage of heavy gas added and the ratio of product ions used to reflect internal energy deposition. Results here also show that upon pulsed introduc tion of heavy gases, empirical optimization of a single frequency resonant excitation signal is no longer needed to obtain good MS/MS spectrometry efficiency. The presence of many low mass-to-charge ratio ions and the absence of side chain cleavages in t he MS/MS spectra of peptides suggests that the propensity for consecutive fragmentations is increased with the pulsed introduction of heavy gases. In addition, by varying the delay time between introduction of the gas and application of the resonant exci tation signal, the amount of fragmentation observed in MS/MS spectra can be changed. (J. Am. Soc. Mass Spectrom., 7, 1194.)

The Dissociation of Dimethylpyrroles: Evidence for Reaction from Isomeric Parent Ions

Tong Lin, Michael R. Asam, and Gary L. Glish

The major dissociation pathways of the [M-H]+ (loss of NH3 or CH4) and the [M+H]+ (loss of NH3 of CH3.) ions from dimethylpyrroles have been determined to occur from isomeric parent ions. For the [M-H]+ ion (formed by loss of a methyl hydrogen), loss of NH3 leads to the formation of the phenylium ion and is preceded by consecutive carbon ring expansions followed by a ring contraction to form protonated aniline. Loss of CH4 occurs after the first carbon ring expansion, which forms protonated picoline. The relative partitioning between the two dissociation paths depends upon the internal energy content of the parent ion; the highest point on the potential energy surface is the second ring expansion step. The [M+H]+ ion reacts through a similar pathway via dihydro analogs of picoline and aniline. The proposed reaction pathways are supported by results of semiemperical molecular orbital calculations. (J. Am. Soc. Mass Spectrom., 7, 930-937.)

Secondary Interactions Affecting the Dissociation Patterns of Arginine-Containing Peptide Ions

Richard W. Vachet, Michael R. Asam, and Gary L. Glish

An explanation is proposed for the dominance of arginine in the dissociation patterns of peptides. Experiments measuring the kinetic energy lost by parent ions of a number of arginine-containing peptides in the formation of particular product ions provide a means of gauging the amount of energy required to observe the dissociation. It is proposed that the higher amounts of energy needed to observe dissociation adjacent to an arginine residue are due to secondary interactions between the arginine side chain and an adjacent amino acid. The appearance of the (bn-1 + OH) ion in the MS/MS spectra of many arginine-containing peptides and data acquired on a quadrupole ion trap help support these findings. We further suggest that the differences in the dissociation between peptides with arginine and those without may be due to the predominance of different reaction mechanisms, i.e., charge-remote versus charge-directed. ( J. Am. Chem. Soc., 118, 6252-6256.)

Reactions of Phenylium Cations with Small Oxygen- and Nitrogen-Containing Molecules

Yasmine A. Ranasinghe and Gary L. Glish

The reactions of phenylium with water and ammonia and their methyl homologues have been investigated using a quadrupole ion trap and semiemperical molecular orbital calculations. The results indicate that both types of molecules react with phenylium through lone pair electrons even though, for methyl-containing compounds, insertion into a C-H bond would lead to more stable products. For the excited adducts formed by reaction with methyl-containing reactant neutrals, the only dissociation observed is loss of a methyl radical. Neutral losses of H2 or CH4, which are more thermodynamically stable, are not observed, which indicates that these reactions are either not kinetically competitive or have high energy transition states due to the fact that the reactions would need to occur via orbital symmetry forbidden 1,2 eliminations. (J. Am. Soc. Mass Spectrom., 7, 473-481.)

Strategy for Pulsed Ionization Methods on a Sector Mass Spectrometer

John D. Lennon, III, David Shinn, Richard W. Vachet, and Gary L. Glish

A method to help facilitate efficient implementation of pulsed ionization methods on a double-focusing sector mass spectrometer is described here. This method involves the addition of an inductive detector between the electric and magnetic sectors. The inductive detector will allow a crude, but complete, time-of-flight mass spectrum to be acquired with as little as a single laser shot, thereby avoiding the necessity of sequentially compiling limited mass ranges as has been dones previously. Mass analys is by the complete sector instrument can be performed simultaneously with the time-of-flight analysis. (Anal. Chem., 68, 845.)

Correlation of Kinetic Energy Losses in High-Energy Collision-Induced Dissociation with Observed Peptide Product Ions

Richard W. Vachet, Andrew D. Winders, and Gary L. Glish

In collision-induced dissociation, some of an incident parent ion's kinetic energy is converted into internal energy upon collision with a neutral target. The kinetic energy is related to the amount of internal energy deposited into any individual ion. To see dissociations of different critical energies on the same time scale, different amounts of internal energy need to be deposited. This should be reflected in the kinetic energy lost by the parent ion in the formation of different product ions. Variable amounts of energy loss in the formation of different peptide product ions are reported here. It is seen that different product ion types (b,y,a) show ordered patterns of energy losses. A greater energy loss is observed for the formation of b-type product ions than for y-type, and even greater energy losses are observed for the formation of a-type product ions. A very good correlation between ion type energy loss and ion mass is observed. Thus, measuring the energy losses in the formation of product ions may provide a means for classifying the product ion type. (Anal. Chem., 68, 522-526.)

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