Alkali metal-cationized serine clusters studied by sonic spray ionization tandem mass spectrometry

Articles

Abstract

Serine solutions containing salts of alkali metals yield magic number clusters of the type (Ser4+C)+, (Ser8+C)+, (Ser12+C)+, and (Ser17+2C)+2 (where C = Li+, Na+, K+, Rb+, or Cs+), in relative abundances which are strongly dependent on the cation size. Strong selectivity for homochirality is involved in the formation of serine tetramers cationized by K+, Rb+, and Cs+. This is also the case for the octamers cationized by the smaller alkalis but there is a strong preference for heterochirality in the octamers cationized by the larger alkali cations. Tandem mass spectrometry shows that the octamers and dodecamers cationized by K+, Rb+, and Cs+ dissociate mainly by the loss of Ser4 units, suggesting that the neutral tetramers are the stable building blocks of the observed larger aggregates, (Ser8+C)+ and (Ser12+C)+. Remarkably, although the Ser4 units are formed with a strong preference for homochirality, they aggregate further regardless of their handedness and, therefore, with a preference for the nominally racemic 4D:4L structure and an overall strong heterochiral preference. The octamers cationized by K+, Rb+, or Cs+ therefore represent a new type of cluster ion that is homochiral in its internal subunits, which then assemble in a random fashion to form octamers. We tentatively interpret the homochirality of these tetramers as a consequence of assembly of the serine molecules around a central metal ion. The data provide additional evidence that the neutral serine octamer is homochiral and is readily cationized by smaller ions.

Supplementary material

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References

  1. 1.
    Hofstadler, S. A.; Griffey, R. H. Analysis of Noncovalent Complexes of DNA and RNA by Mass Spectrometry. Chem. Rev. 2001, 101, 377–390.CrossRefGoogle Scholar
  2. 2.
    Borman, S. Quadruplex Proposals. Chem. Eng. News. 2002, 80, 36–37.CrossRefGoogle Scholar
  3. 3.
    Borman, S. Quadruplex Seen in Human Cells. Chem. Eng. News. 2002, 80, 9.Google Scholar
  4. 4.
    Fukushima, K.; Iwahashi, H. 1:1 Complex of Guanine Quartet with Alkali Metal Cations Detected by Electrospray Ionization Mass Spectrometry. Chem. Commun. 2000, 895–896.Google Scholar
  5. 5.
    Freisinger, E.; Schimanski, A.; Lippert, B. Thymine-Metal Ion Interactions: Relevance for Thymine Quartet Structures. J. Biol. Inorg. Chem. 2001, 6, 378–389.CrossRefGoogle Scholar
  6. 6.
    Koch, K. J.; Aggerholm, T.; Nanita, S. C.; Cooks, R. G. Clustering of Nucleobases with Alkali Metals Studied by Electrospray Ionization Mass Spectrometry: Implications for Mechanisms of Multistrand DNA Stabilization. J. Mass Spectrom. 2002, 37, 676–686.CrossRefGoogle Scholar
  7. 7.
    Tirumala, S.; Davis, J. T. Self-Assembled Ionophores: An Isoguanosine-K+ Octamer. J. Am. Chem. Soc. 1997, 119, 2769–2776.CrossRefGoogle Scholar
  8. 8.
    Mezzina, E.; Mariani, P.; Itri, R.; Masiero, S.; Pieraccini, S.; Spada, G. P.; Spinozzi, F.; Davis, J. T.; Gottarelli, G. The Self-Assembly of a Lipophilic Guanosine Nucleoside into Polymeric Columnar Aggregates: The Nucleoside Structure Contains Sufficient Information to Drive the Process Towards a Strikingly Regular Polymer. Chem. Eur. J. 2001, 7, 388–395.CrossRefGoogle Scholar
  9. 9.
    Aggerholm, T.; Nanita, S. C.; Koch, K.; Cooks, R. G. Clustering of Nucleosides in the Presence of Alkali Metals: Biologically Relevant Quartets of Guanosine, Deoxyguanosine, and Uridine Observed by Electrospray Ionization Tandem Mass Spectrometry. J. Mass Spectrom. 2003, 38, 87–97.CrossRefGoogle Scholar
  10. 10.
    Canty, A. J.; Colton, R.; D’Agostino, A.; Traeger, J. C. Positive and Negative Ion Electrospray Mass Spectrometric Studies of Some Amino Acids and Glutathione, and Their Interactions with Alkali Metal Ions and Methylmercury. II. Inorg. Chim. Acta. 1994, 223, 103–107.CrossRefGoogle Scholar
  11. 11.
    Julian, R. R.; 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.CrossRefGoogle Scholar
  12. 12.
    Mark, T. D. Mass Spectrometry of Clusters. Adv. Mass Spectrom. 1995, 13, 71–94.Google Scholar
  13. 13.
    Zhou, S. L.; Hamburger, M. Formation of Sodium Cluster Ions in Electrospray Mass Spectrometry. Rapid Commun. Mass Spectrom. 1996, 10, 797–800.CrossRefGoogle Scholar
  14. 14.
    Zhang, D.; Wu, L.; Koch, K. J.; Cooks, R. G. Arginine Clusters Generated by Electrospray Ionization and Identified by Tandem Mass Spectrometry. Eur. Mass Spectrom. 1999, 5, 353–361.CrossRefGoogle Scholar
  15. 15.
    Zhang, D.; Cooks, R. G. Doubly-Charged Cluster Ions, [(NaCl)m(Na)2]2+: Magic Numbers, Dissociation, and Structure. Int. J. Mass Spectrom. 2000, 195/196, 667–684.CrossRefGoogle Scholar
  16. 16.
    Justes, D. R.; Mitric, R.; Moore, N. A.; Bonacic-Koutecky, V.; Castleman, A. W. Theoretical and Experimental Consideration of the Reactions between VxOy+ and Ethylene. J. Am. Chem. Soc. 2003, 125, 6289–6299.CrossRefGoogle Scholar
  17. 17.
    Justes, D. R.; Moore, N. A.; Castleman, A. W. Reactions of Vanadium and Niobium Oxides with Methanol. J. Phys. Chem. B. 2004, 108, 3855–3862.CrossRefGoogle Scholar
  18. 18.
    Dermota, T. E.; Zhong, Q.; Castleman, A. W. Ultrafast Dynamics in Cluster Systems. Chem. Rev. 2004, 104, 1861–1886.CrossRefGoogle Scholar
  19. 19.
    Nemes, P.; Schlosser, G.; Vékey, K. Amino Acid Cluster Formation Studied by Electrospray Ionization Mass Spectrometry. J. Mass Spectrom. 2005, 40, 43–49.CrossRefGoogle Scholar
  20. 20.
    Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. Electrospray Ionization for Mass-Spectrometry of Large Biomolecules. Science. 1989, 246, 64–71.CrossRefGoogle Scholar
  21. 21.
    Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. Electrospray Ionization-Principles and Practice. Mass Spectrom. Rev. 1990, 9, 37–70.CrossRefGoogle Scholar
  22. 22.
    Ramsey, R. S.; Van Berkel, G. J.; McLuckey, S. A.; Glish, G. L. Determination of Pyrimidine Cyclobutane Dimers by Electrospray Ionization/Ion Trap Mass Spectrometry. Biol. Mass Spectrom. 1992, 21, 347–352.CrossRefGoogle Scholar
  23. 23.
    Little, D. P.; Chorush, R. A.; Speir, J. P.; Senko, M. W.; Kelleher, N. L.; McLafferty, F. W. Rapid Sequencing of Oligonucleotides by High-Resolution Mass Spectrometry. J. Am. Chem. Soc. 1994, 116, 4893–4897.CrossRefGoogle Scholar
  24. 24.
    Przybylski, M.; Glocker, M. O. Electrospray Mass Spectrometry of Biomacromolecular Complexes with Noncovalent Interactions—New Analytical Perspectives for Supramolecular Chemistry and Molecular Recognition Processes. Angew. Chem. Int. Ed. 1996, 35, 806–826.CrossRefGoogle Scholar
  25. 25.
    Loo, J. A. Studying Noncovalent Protein Complexes by Electrospray Ionization Mass Spectrometry. Mass Spectrom. Rev. 1997, 16, 1–23.CrossRefGoogle Scholar
  26. 26.
    Loo, J. A. Electrospray Ionization Mass Spectrometry: A Technology for Studying Noncovalent Macromolecular Complexes. Int. J. Mass Spectrom. 2000, 200, 175–186.CrossRefGoogle Scholar
  27. 27.
    Shelimov, K. B.; Jarrold, M. F. “Denaturation” and Refolding of Cytochrome c in Vacuo. J. Am. Chem. Soc. 1996, 118, 10313–10314.CrossRefGoogle Scholar
  28. 28.
    Valentine, S. J.; Anderson, J. G.; Ellington, A. D.; Clemmer, D. E. Disulfide-Intact and -Reduced Lysozyme in the Gas Phase: Conformations and Pathways of Folding and Unfolding. J. Phys. Chem. B. 1997, 101, 3891–3900.CrossRefGoogle Scholar
  29. 29.
    Hirabayashi, A.; Sakairi, M.; Koizumi, H. Sonic Spray Ionization Method for Atmospheric Pressure Ionization Mass Spectrometry. Anal. Chem. 1994, 66, 4557–4559.CrossRefGoogle Scholar
  30. 30.
    Hirabayashi, A.; Sakairi, M.; Koizumi, H. Sonic Spray Mass Spectrometry. Anal. Chem. 1995, 67, 2878–2882.CrossRefGoogle Scholar
  31. 31.
    Shiea, J.; Wang, W.-S.; Wang, C.-H.; Chen, P.-S.; Chou, C.-H. Analysis of a Reactive Dimethylenedihydrothiophene in Methylene Chloride by Low-Temperature Atmospheric Pressure Ionization Mass Spectrometry. Anal. Chem. 1996, 68, 1062–1066.CrossRefGoogle Scholar
  32. 32.
    Yamaguchi, K. Cold-Spray Ionization Mass Spectrometry: Principle and Applications. J. Mass Spectrom. 2003, 38, 473–490.CrossRefGoogle Scholar
  33. 33.
    Takats, Z.; Wiseman, J. M.; Gologan, B.; Cooks, R. G. Electrosonic Spray Ionization: A Gentle Technique for Generating Folded Proteins and Protein Complexes in the Gas Phase and for Studying Ion-Molecule Reactions at Atmospheric Pressure. Anal. Chem. 2004, 76, 4050–4058.CrossRefGoogle Scholar
  34. 34.
    Wiseman, J. M.; Takáts, Z.; Gologan, B.; Davisson, V. J.; Cooks, R. G. Direct Characterization of Enzyme-Substrate Complexes by Using Electrosonic Spray Ionization Mass Spectrometry. Angew. Chem. Int. Ed. 2005, 44, 913–916.CrossRefGoogle Scholar
  35. 35.
    Takats, Z.; Nanita, S. C.; Cooks, R. G.; Schlosser, G.; Vekey, K. Amino Acid Clusters Formed by Sonic Spray Ionization. Anal. Chem. 2003, 75, 1514–1523.CrossRefGoogle Scholar
  36. 36.
    Myung, S.; Julian, R. R.; Nanita, S. C.; Cooks, R. G.; Clemmer, D. E. Formation of Nanometer-Scale Serine Clusters by Sonic Spray. J. Phys. Chem. B. 2004, 108, 6105–6111.CrossRefGoogle Scholar
  37. 37.
    Zhang, D.; Koch, K. J.; Tao, W. A.; Cooks, R. G. Proceedings of the 48th ASMS Conference on Mass Spectrometry and Allied Topics; Long Beach, CA, June 2000.Google Scholar
  38. 38.
    Cooks, R. G.; Zhang, D.; Koch, K. J.; Gozzo, F. C.; Eberlin, M. N. Chiroselective Self-Directed Octamerization of Serine: Implications for Homochirogenesis. Anal. Chem. 2001, 73, 3646–3655.CrossRefGoogle Scholar
  39. 39.
    Hodyss, R.; Julian, R. R.; Beauchamp, J. L. Spontaneous Chiral Separation in Noncovalent Molecular Clusters. Chirality. 2001, 13, 703–706.CrossRefGoogle Scholar
  40. 40.
    Counterman, A. E.; Clemmer, D. E. Magic Number Clusters of Serine in the Gas Phase. J. Phys. Chem. B. 2001, 105, 8092–8096.CrossRefGoogle Scholar
  41. 41.
    Julian, R. R.; Hodyss, R.; Kinnear, B.; Jarrold, M.; Beauchamp, J. L. Nanocrystalline Aggregation of Serine Detected by Electrospray Ionization Mass Spectrometry: Origin of the Stable Homochiral Gas Phase Serine Octamer. J. Phys. Chem. B. 2002, 106, 1219–1228.CrossRefGoogle Scholar
  42. 42.
    Kong, X.; Tsai, I.-A.; Sabu, S.; Han, C.-C.; Lee, Y. T.; Chang, H.-C.; Tu, S.-Y.; Kung, A. H.; Wu, C.-C. Progressive Stabilization of Zwitterionic Structures in [H(Ser)2-8]+ Studied by Infrared Photodissociation Spectroscopy. Angew. Chem. Int. Ed. 2006, 45, 4130–4134.CrossRefGoogle Scholar
  43. 43.
    Koch, K. J.; Gozzo, F. C.; Zhang, D.; Eberlin, M. N.; Cooks, R. G. Serine octamer metaclusters: Formation, Structure Elucidation, and Implications for Homochiral Polymerization. Chem. Commun. 2001, 1854–1855.Google Scholar
  44. 44.
    Koch, K. J.; Gozzo, F. C.; Nanita, S. C.; Takats, Z.; Eberlin, M. N.; Cooks, R. G. Chiral Transmission between Amino Acids: Chirally-Selective Amino Acid Substitution in the Serine Octamer as a Possible Step in Homochirogenesis. Angew. Chem. Int. Ed. 2002, 41, 1721–1724.CrossRefGoogle Scholar
  45. 45.
    Schalley, C. A.; Weis, P. Unusually Stable Magic Number Clusters of Serine with a Surprising Preference for Homochirality. Int. J. Mass Spectrom. 2002, 221, 9–19.CrossRefGoogle Scholar
  46. 46.
    Takats, Z.; Nanita, S. C.; Cooks, R. G. Serine Octamer Reactions: Indicators of Prebiotic Relevance. Angew. Chem. Int. Ed. 2003, 42, 3521–3523.CrossRefGoogle Scholar
  47. 47.
    Takats, Z.; Nanita, S. C.; Schlosser, G.; Vekey, K.; Cooks, R. G. Atmospheric Pressure Gas-Phase H/D Exchange of Serine Octamers. Anal. Chem. 2003, 75, 6147–6154.CrossRefGoogle Scholar
  48. 48.
    Ustyuzhanin, P.; Ustyuzhanin, J.; Lifshitz, C. An Electrospray Ionization-Flow Tube Study of H/D Eexchange in Protonated Serine. Int. J. Mass Spectrom. 2003, 223–224, 491–498.CrossRefGoogle Scholar
  49. 49.
    Geller, O.; Lifshitz, C. An Electrospray Ionization-Flow Tube Study of H/D Exchange in the Protonated Serine Dimer and Protonated Serine Dipeptide. Int. J. Mass Spectrom. 2003, 227, 77–85.CrossRefGoogle Scholar
  50. 50.
    Julian, R. R.; Myung, S.; Clemmer, D. E. Proceedings of the 52nd ASMS Conference on Mass Spectrometry and Allied Topics; Nashville, TN, May 2004.Google Scholar
  51. 51.
    Julian, R. R.; Myung, S.; Clemmer, D. E. Spontaneous Anti-Resolution in Heterochiral Clusters of Serine. J. Am. Chem. Soc. 2004, 126, 4110–4111.CrossRefGoogle Scholar
  52. 52.
    Takats, Z.; Cooks, R. G. Thermal Formation of Serine Octamer Ions. Chem. Commun. 2004, 444–445.Google Scholar
  53. 53.
    Nanita, S. C.; Takats, Z.; Cooks, R. G. Proceedings of the 52nd ASMS Conference on Mass Spectrometry and Allied Topics; Nashville, TN, May 2004.Google Scholar
  54. 54.
    Nanita, S. C.; Takats, Z.; Myung, S.; Clemmer, D. E.; Cooks, R. G. Chiral Enrichment of Serine Via Formation, Dissociation, and Soft-Landing of Octameric Cluster Ions. J. Am. Soc. Mass Spectrom. 2004, 15, 1360–1365.CrossRefGoogle Scholar
  55. 55.
    Hwang, H. Y.; Lin, C.; Oh, H.; Breuker, K.; Carpenter, B. K.; McLafferty, F. W. Proceedings of the 52nd ASMS Conference on Mass Spectrometry and Allied Topics; Nashville, TN, May 2004.Google Scholar
  56. 56.
    Hvelplund, P.; Rangama, J.; Liu, B.; Nielsen, A. B.; Nielsen, S. B.; Tomita, S. Proceedings of the 52nd ASMS Conference on Mass Spectrometry and Allied Topics; Nashville, TN, May 2004.Google Scholar
  57. 57.
    O’Hair, R. A. J.; Gronert, S.; Fagin, A. Proceedings of the 52nd ASMS Conference on Mass Spectrometry and Allied Topics; Nashville, TN, May 2004.Google Scholar
  58. 58.
    Mazurek, U.; Reuben, B. G.; McFarland, M. A.; Marshall, A. G.; Lifshitz, C. Proceedings of the 52nd ASMS Conference on Mass Spectrometry and Allied Topics; Nashville, TN, May 2004.Google Scholar
  59. 59.
    Gronert, S.; O’Hair, R. A. J.; Fagin, A. E. Ion/Molecule Reactions of the Protonated Serine Octamer. Chem. Commun. 2004, 1944–1945.Google Scholar
  60. 60.
    Mazurek, U.; McFarland, M. A.; Marshall, A. G.; Lifshitz, C. Isolation of Isomers Based on Hydrogen/Deuterium Exchange in the Gas Phase. Eur. J. Mass Spectrom. 2004, 10, 755–758.CrossRefGoogle Scholar
  61. 61.
    Mazurek, U.; Geller, O.; Lifshitz, C.; McFarland, M. A.; Marshall, A. G.; Reuben, B. G. Protonated Serine Octamer Cluster: Structure Elucidation by Gas-Phase H/D Exchange Reactions. J. Phys. Chem. A. 2005, 109, 2107–2112.CrossRefGoogle Scholar
  62. 62.
    Nanita, S. C.; Cooks, R. G. Negatively-Charged Halide Adducts of Homochiral Serine Octamers. J. Phys. Chem. B. 2005, 109, 4748–4753.CrossRefGoogle Scholar
  63. 63.
    Nanita, S. C.; Cooks, R. G. Serine Octamers: Cluster Formation, Reactions, and Implications for Biomolecule Homochirality. Angew. Chem. Int. Ed. 2006, 45, 554–569.CrossRefGoogle Scholar
  64. 64.
    Wong, S. S.; Röllgen, F. W. The Effect of a Glycerol Matrix on the Cluster Ion Formation from Salts in Secondary Ion Mass Spectrometry. Int. J. Mass Spectrom. Ion Processes. 1986, 70, 135–144.CrossRefGoogle Scholar
  65. 65.
    Myung, S.; Fioroni, M.; Julian, R. R.; Koeniger, S. L.; Baik, M.-H.; Clemmer, D. E. Chirally Directed Formation of Nanometer-Scale Proline Clusters. J. Am. Chem. Soc. 2006, 128, 10833–10839.CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2007

Authors and Affiliations

  • Sergio C. Nanita
    • 1
  • Ewa Sokol
    • 1
  • R. Graham Cooks
    • 1
  1. 1.Department of ChemistryPurdue UniversityWest LafayetteUSA
  2. 2.DuPont Crop ProtectionStine-Haskell Research CenterNewarkUSA

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