Abstract
The gas-phase interaction of sodiated amino acids and sodiated amino acid methyl esters with various deuterium donors is investigated by combining results of H/D exchange reactions with those from density functional theory and molecular dynamics calculations. Discrepancy between experimentally and theoretically obtained structures for sodium cationized amino acids is explained by deuterium donor caused perturbation of the most stable amino acid conformation. Detailed study of H/D exchange mechanism on sodiated amino acids shows that the H/D exchange reaction is preceded by a multistep quasi-isoenergetic transition (perturbation) from a charge solvated to zwitterionic structure in the amino acid. Although the computation refers to the system AlaNa+ and D2O, these mechanisms apply to all amino acids, except those where a functional side-chain group takes part in the perturbation process. The suggested perturbation mechanism applies also for other deuterium donors such as CD3OD or even ND3 and indicates that a single water molecule suffices to convert the sodiated amino acid from charge solvated to zwitterionic form.
Article PDF
Similar content being viewed by others
References
Gard, E.; Willard, D.; Bregar, J.; Green, M. K.; Lebrilla, C. B. Site Specificity in the H-D Exchange Reaction of Gas-Phase Protonated Amino Acids with CH3OD. Org. Mass Spectrom. 1993, 28, 1632–1639.
Campbell, S.; Rodgers, M. T.; Marzluff, E. M.; Beauchamp, J. L. Deuterium Exchange as Probe of Biomolecule Structure. Fundamental Studies of Gas-Phase H/D Exchange Reactions of Protonated Glycine Oligomers with D2O, CD3OD, CD3CO2D, and ND3. J. Am. Chem. Soc. 1995, 117, 12840–12854.
Green, M. K.; Lebrilla, C. B. Ion-Molecule Reactions as Probes of Gas-Phase Structures of Peptides and Proteins. Mass Spectrom. Rev. 1997, 16, 53–71.
Wyttenbach, T.; Bowers, M. T. Gas Phase Conformations of Biological Molecules: The Hydrogen/Deuterium Exchange Mechanism. J. Am. Soc. Mass Spectrom. 1999, 10, 9–14.
He, F.; Marshall, A. G. Weighted Quasi-Newton and Variable-Order, Variable-Step Adams Algorithm for Determining Site-Specific Reaction Rate Constants. J. Phys. Chem. A 2000, 104, 562–567.
He, F.; Marshall, A. G.; Freitas, M. A. Assignment of Gas-Phase Dipeptide Amide Hydrogen Exchange Rate Constants by Site-Specific Substitution: GlyGly. J. Phys. Chem. B 2001, 105, 2244–2249.
Rožman, M.; Kazazić, S.; Klasinc, L.; Srzić, D. Kinetic of Gas-Phase Hydrogen/Deuterium Exchange and Gas-Phase Structure of Protonated Phenylalanine, Proline, Tyrosine, and Tryptophan. Rapid Commun. Mass Spectrom. 2003, 17, 2769–2772.
Lifshitz, C. A Review of Gas-Phase H/D Exchange Experiments: The Protonated Arginine Dimer and Bradykinin Nonapeptide Systems. Int. J. Mass Spectrom. 2004, 234, 63–70.
Rožman, M. The Gas-Phase H/D Exchange Mechanism of Protonated Amino Acids. J. Am. Soc. Mass Spectrom. 2005, 16, 1846–1852.
Cox, H. A.; Julian, R. R.; Lee, S. W.; Beauchamp, J. L. Gas-Phase H/D Exchange of Sodiated Glycine Oligomers with ND3: Exchange Kinetics Do Not Reflect Parent Ion Structures. J. Am. Chem. Soc. 2004, 126, 6485–6490.
Rožman, M. Gas Phase Structure of the Sodiated Amino Acids Probed by H/D Exchange Reactions. Croat. Chem. Acta 2005, 78, 185–188.
Curtiss, L. A.; Redfern, P. C.; Raghavachari, K.; Rassolov, V.; Pople, J. A. Gaussian-3 Theaory Using Reduced Møller-Plesset order. J. Chem. Phys. 1999, 110, 4703–4709.
Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03 Revision B.05; Gaussian, Inc.: Pittsburgh, PA, 2003.
Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. MacroModel—An Integrated Software System for Modeling Organic and Bioorganic Molecules Using Molecular Mechanics. J. Comput. Chem. 1990, 11, 440–467.
Hoyau, S.; Norrman, K.; McMahon, T. B.; Ohanessian, G. A. Quantitative Basis for a Scale of Na+ Affinities of Organic and Small Biological Molecules in the Gas Phase. J. Am. Chem. Soc. 1999, 121, 8864–8875.
Wyttenbach, T.; Witt, M.; Bowers, M. T. On the Stability of Amino Acid Zwitterions in the Gas Phase: The Influence of Derivatization, Proton Affinity, and Alkali Ion Addition. J. Am. Chem. Soc. 2000, 122, 3458–3464.
Gapeev, A.; Dunbar, R. C. Na+ Affinities of Gas-Phase Amino Acids by Ligand Exchange Equilibrium. Int. J. Mass Spectrom. Ion Processes 2003, 228, 825–839.
Lemoff, A. S.; Bush, M. F.; Williams, E. R. Binding Energies of Water to Sodiated Valine and Structural Isomers in the Gas Phase: The Effect of Proton Affinity on Zwitterion Stability. J. Am. Chem. Soc. 2003, 125, 13576–13584.
Marino, T.; Russo, N.; Toscano, M. Gas-Phase Metal Ion (Li+, Na+, Cu+) Affinities of Glycine and Alanine. J. Inorg. Biochem. 2000, 79, 179–185.
Marino, T.; Russo, N.; Toscano, M. Potential Energy Surfaces for the Gas-Phase Interaction Between α-Alanine and Alkali Metal Ions (Li+, Na+, K+). A Density Functional Study. Inorg. Chem. 2001, 40, 6439–6443.
Karas, M.; Glückmann, M.; Schäfer, J. Ionization in Matrix-Assisted Laser Desorption/Ionization: Singly Charged Molecular Ions are the Lucky Survivors. J. Mass Spectrom. 2000, 35, 1–12.
Kapota, C.; Lemaire, J.; Maitre, P.; Ohanessian, G. Vibrational Signature of Charge Solvation vs. Salt Bridge Isomers of Sodiated Amino Acids in the Gas Phase. J. Am. Chem. Soc. 2004, 126, 6485–6490.
Hoyau, S.; Ohanessian, G. Interaction of Alkali Metal Cations (Li+-CS+) with Glycine in the Gas Phase: A Theoretical Study. Chem. Eur. J. 1998, 4, 1561–1569.
Hoyau, S.; Pelicier, J. P.; Rogalewicz, F.; Hoppilliard, Y.; Ohanessian, G. Complexation of Glycine by Atomic Metal Cations in the Gas Phase. Eur. J. Mass Spectrom. 2001, 7, 303–311.
Author information
Authors and Affiliations
Corresponding author
Additional information
Published online December 15, 2005
Rights and permissions
About this article
Cite this article
Rožman, M., Bertoša, B., Klasinc, L. et al. Gas phase H/D exchange of sodiated amino acids: Why do we see zwitterions?. The official journal of The American Society for Mass Spectrometry 17, 29–36 (2006). https://doi.org/10.1016/j.jasms.2005.08.017
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1016/j.jasms.2005.08.017