Abstract
Protonated complexes of amino acids and underivatized β-cyclodextrin, produced by electrospray ionization and trapped in the Fourier transform mass spectrometer, undergo formation of ternary complexes when reacted with alkyl amine. Based on the reactivities of the protonated amino acid complexes with alkylamines, the reactivities of the corresponding amino acid esters, and partially derivatized β-cyclodextrin hosts, we conclude that the ternary complexes are salt-bridge zwitterionic species composed of amino acid zwitterions and protonated alkylamine all interacting with the hydroxyl groups on the narrow rim of the cyclodextrin. Molecular modeling calculations and experimental results suggest that the interactions of the amino acids with the rims contribute greatly to the formation of the zwitterionic species.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Vickers, S.; Polsky, S. L. The biotransformation of nitrogen containing xenobiotics to lactams. Curr. Drug Metab. 2000, 1, 357–389.
Kvamme, E.; Roberg, B.; Torgner, I. A. Glutamine transport in brain mitochondria. Neurochem. Int. 2000, 37, 131–138.
Twhwaties, D. T.; Stevens, B. C.. Exp. Physiol. 1999, 84, 275–284.
Pineda, M.; Fernandez, E.; Torrents, D.; Esteves, R.; Lopez, C.; Camps, M.; Lloberas, J.; Zorzano, A.; Palacin, M., et al. Identification of a membrane protein, LAT-2, that co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids. J. Biol. Chem. 1999, 274, 19738–19744.
Hatanaka, T.; Kamon, T.; Uozumi, C.; Morigaki, S.; Aiba, T.; Katayama, K.; Koizumi, T. Influence of pH on skin permeation of amino acids. J. Pharm. Pharmacol. 1996, 48, 675–679.
Wu, X.; Geroge, R. L.; Huang, W.; Wang, H.; Conway, S. J.; Leibach, H. F.; Ganapathy, V. Biochim. Biophys. Acta 2000, 1466, 315–327.
Raposo, C.; Wilcox, C. S. The intramolecular salt effect in chiral auxiliaries. Enhanced diastereoselectivity in a nitrile oxide cycloaddition via rational transition state stabilization. Tetrahedron Lett. 1999, 40, 1285–1288.
Spencer, T. A.; Onofrey, T. J.; Cann, R. O.; Russel, J. S.; Lee, L. E.; Blanchard, D. E.; Castro, A.; Gu, P.; Jiang, G.; Shecter, I. Zwitterionic sulfobetaine inhibitors of squalene synthase. J. Org. Chem. 1999, 64, 807–818.
Theodore, T. R.; Van Zandt, R.; Carpenter, R. H. Preliminary evaluation of a fixed dose of zwitterionic piperazine (TVZ-7) in clinical cancer. CANCER Biother. Rad. 1997, 12, 351–353.
Kim, E.; Paliwal, S.; Wilcox, C. S. Measurements of molecular electrostatic field effects in edge-to-face aromatic interactions and CH-interactions with implications for protein folding and molecular recognition. J. Am. Chem. Soc. 1998, 120, 11192–11193.
Gordon, M. S.; Jensen, J. H. Understanding the hydrogen bond using quantum chemistry. Acc. Chem. Res. 1996, 29, 536–543.
Jensen, J. H.; Gordon, M. S. On the number of water molecules necessary to stabilize the glycine zwitterion. J. Am. Chem. Soc. 1995, 117, 8159–8170.
Chapo, C. J.; Paul, J. B.; Provencal, R. A.; Roth, K.; Saykally, R. J. Is arginine zwitterionic or neutral in the gas phase? Results from IR cavity ringdown spectroscopy. J. Am. Chem. Soc. 1998, 120, 12956–12957.
Ryan, R. J.; Hodyss, R.; Beauchamp, J. L. Salt bridge stabilization of charged zwitterionic arginine aggregates in the gas phase. J. Am. Chem. Soc. 2001, 123, 3577–3583.
Suenram, R. D.; Lovas, F. J. Millimeter wave spectrum of glycine. A new conformer. J. Am. Chem. Soc. 1980, 102, 7180–7184.
Wang, X. B.; Broadus, K. M.; Wang, L. S.; Kass, S. R. Photo-detachment of the first zwitterionic anions in the gas phase: probing intramolecular coulomb repulsion and attraction. J. Am. Chem. Soc. 2000, 122, 8305–8306.
Kassab, E.; Langlet, J.; Evleth, E.; Akacem, Y. Theoretical study of solvent effect on intramolecular proton transfer of glycine. J. Molec. Struct. (Theochem) 2000, 531, 267–282.
Broadus, K. M.; Kass, S. R. Probing electrostatic effects: Formation and characterization of zwitterionic ions and their “neutral” counterparts in the gas phase. J. Am. Chem. Soc. 2000, 122, 9014–9018.
Jockush, R. A.; Price, W. D.; Williams, E. R. Structure of cationized arginine (Arg.Mz+, M = H, Li, Na, K, Rb, and Cs) in the gas phase: Further evidence for zwitterionic arginine. J. Phys. Chem. A 1999, 103, 9266–9274.
Price, W. D.; Jockusch, R. A.; Williams, E. R. Is arginine a zwitterion in the gas phase? J. Am. Chem. Soc. 1997, 119, 11988–11989.
Wyttenbach, T.; Witt, M.; Bowers, M. T. On the stability of amino acid zwitterions in the gas phase: The influence of derivatization, proton affinty, and alkali ion addition. J. Am. Chem. Soc. 2000, 122, 3458–3464.
Wyttenbach, T.; Bushnell, J. E.; Bowers, M. T. Salt bridge structures in the absence of solvent? The case for the oligoglycines. J. Am. Chem. Soc. 1998, 120, 5098–5103.
Wyttenbach, T.; Witt, M.; Bowers, M. T. On the question of salt bridges of cationized amino acids in the gas phase: Glycine and arginine. Int. J. Mass Spectrom. 1999, 182, 243–252.
Wang, W.; Pu, X.; Zheng, W.; Wong, N. B.; Tian, A. Some theoretical observations on the 1:1 glycine zwitterion-water complex. J. Molec. Struct. (Theochem) 2003, 626, 127–132.
Julian, R. R.; Beauchamp, J. L.; Goddard, W. A., III Cooperative salt bridge stabilization of gas-phase zwitterions in neutral arginine clusters. J. Phys. Chem. A 2002, 106, 32–34.
Jockusch, R. A.; Lemoff, A. S.; Williams, E. R. Hydration of valine-cation complexes in the gas phase: On the number of water molecules necessary to form a zwitterion. J. Phys. Chem. A 2001, 105, 10929–10942.
Jockusch, R. A.; Lemoff, A. S.; Williams, E. R. Effect of metal ion and water coordination on the structure of a gas-phase amino acid. J. Am. Chem. Soc. 2001, 123, 12255–12265.
Cerda, B. A.; Wesdemiotis, C. Li+, Na+, and K+ Binding to the DNA and RNA Nucleobases. Bond Energies and Attachment Sites from the Dissociation of Metal Ion-Bound Heterodimers. J. Am. Chem. Soc. 1996, 118, 11884–11892.
Kish, M. M.; Ohanessian, G.; Wesdemiotis, C. The Na+ affinities of amino acids: side-chain substituent effects. Int. J. Mass Spectrom. 2003, 227, 509–524.
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.
Wong, C. H. S.; Siu, F. M.; Ma, N. L.; Tsang, C. W. A theoretical study of potassium cation-glycine (K+-Gly) interactions. J. Mol. Struct. (Theochem) 2002, 588, 9–16.
Talley, J. M.; Cerda, Blas A.; Ohanessian, G.; Wesdemiotis, C. Alkali metal ion binding to amino acids versus their methyl esters: Affinity trends and structural changes in the gas phase. Chem-Eur J 2002, 8, 1377–1388.
Ryzhov, V.; Dunbar, R. C.; Cerda, B.; Wesdemiotis, C. Cation—Effects in the complexation of Na+ and K+ with Phe, Tyr, and Trp in the gas phase. J. Am. Soc. Mass Spectrom. 2000, 11, 1037–1046.
Locke, M. J.; Hunter, R. L.; McIver, R. T., Jr. Experimental Determination of the Acidity and Basicity of Glycine in the Gas Phase. J. Am. Chem. Soc. 1979, 101, 272–273.
Siu, F. M.; Ma, N. L.; Tsang, C. W. Cation-pi interactions in sodiated phenylalanine complexes: Is phenylalanine in the charge-solvated or zwitterionic form? J. Am. Chem. Soc. 2001, 123, 3397–3398.
Minyaev, R. M.; Starikov, A. G.; Minkin, V. Stabilization of the glycine zwitterionic form by complexation with Na+ and Cl−: An ab initio study. Mendelev. Commun. 2000, 2, 43–44.
Winkle, L. J. V.; Campione, A. L.; Gorman, J. M. Na+-independent transport of basic and zwitterionic amino acids in mouse blastocysts by a shared system and by processes which distinguish between these substrates. J. Biol. Chem. 1988, 263, 3150–3163.
Cerda, B. A.; Wesdemiotis, C. Zwitterionic versus charge-solvated structures in the binding of arginine to alkali metal ions in the gas phase. Analyst (Cambridge, U.K.) 2000, 125, 657–660.
Rak, J.; Skurski, P.; Gutowski, M. An ab initio study of the betaine anion-dipole-bound anionic state of a model zwitterion system. J. Chem. Phys. 2001, 114, 10673–10681.
Ramirez, J.; He, F.; Lebrilla, C. B. Gas-phase chiral differentiation of amino acid guests in cyclodextrin hosts. J. Am. Chem. Soc. 1998, 120, 7387–7388.
Ramirez, J.; Ahn, S.; Grigorean, G.; Lebrilla, C. B. Evidence for the formation of gas-phase inclusion complexes with cyclodextrins and amino acids. J. Am. Chem. Soc. 2000, 122, 6881–6890.
Ciucanu, I.; Kerek, F. Derivatization of Cyclodextrins. Carbohydr. Res. 1984, 131, 209–217.
Gard, E. E.; Green, M. K.; Warren, H.; Camara, E. J. O.; He, F.; Penn, S. G.; Lebrilla, C. B. A dual vacuum chamber Fourier transform mass spectrometer with rapidly interchangeable FAB, MALDI, and ESI Sources: Electrospray results. Int. J. Mass Spectrom. Ion Processes 1996, 157/158, 115–127.
Ahn, S.; Ramirez, J.; Grigorean, G.; Lebrilla, C. B. Chiral Recognition in gas-phase cyclodextrin: amino acid complexes—Is the three point interaction still valid in the gas phase? J. Am. Soc. Mass Spectrom. 2001, 12, 278–287.
Penn, S. G.; He, F.; Lebrilla, C. B. Peptides complexed to cyclodextrin fragment rather than dissociate when subjected to blackbody infrared radiation D. J. Phys. Chem. 1998, 102, 9119–9126.
Gronert, S.; Pratt, L. M.; Mogali, S. Sustituent effects in gas-phase substitutions. Solvation reverses SN2 Substituent Effects. J. Am. Chem. Soc. 2001, 123, 3081–3091.
Flores, A. E.; Gronert, S. The gas-phase reactions of dianions with alkyl bromides: Direct identification of S(N)2 and E2 products. J. Am. Chem. Soc. 1999, 121, 2627–2628.
Meot-Ner (Mautner), M. The ionic hydrogen bond and ion solvation. 1. NH+—O, NH+—N, and OH+—O bonds. Correlations with proton affinity. Deviations due to structural effects. J. Am. Chem. Soc. 1984, 106, 257–264.
Meot-Ner (Mautner), M. The ionic hydrogen bond and ion solvation. 2. Solvation of onium ions by one to seven water molecules. Relations between monomolecular, specific, and bulk hydrogen. J. Am. Chem. Soc. 1984, 106, 1265–1272.
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.
Jensen, F. Structure and stability of complexes of glycine and glycine methyl analogues with H+, Li+, and Na+. J. Am. Chem. Soc. 1992, 114, 9533–9537.
Hunter, E. P. L.; Lias, S. G. Evaluated gas phase basicities and proton affinities of molecules: An update. J. Phys. Chem. Ref. Data 1998, 27, 413–656.
Author information
Authors and Affiliations
Corresponding author
Additional information
Published online December 15, 2004
Rights and permissions
About this article
Cite this article
Ahn, S., Cong, X., Lebrilla, C.B. et al. Zwitterion formation in gas-phase cyclodextrin complexes. J Am Soc Mass Spectrom 16, 166–175 (2005). https://doi.org/10.1016/j.jasms.2004.10.007
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1016/j.jasms.2004.10.007