Skip to main content
SpringerLink
Log in

Structures of a n * Ions Derived from Protonated Pentaglycine and Pentaalanine: Results from IRMPD Spectroscopy and DFT Calculations

  • Research Article
  • Published:
Journal of The American Society for Mass Spectrometry

Abstract

Infrared multiple-photon dissociation (IRMPD) spectroscopy and DFT calculations have been used to probe the most stable structures of a 3 * and a 4 * ions derived from both protonated pentaglycine (denoted G5) and pentaalanine (A5). The a 3 * and a 4 * ions derived from protonated A5 feature a CHR=N-CHR’- group at the N-terminus and an oxazolone ring at the C-terminus, as proposed previously [J. Am. Soc. Mass Spectrom. 19, 1788–1798 (2008)]. The isomeric a 4 * ion derived from A5 with a 3,5-dihydro-4H-imidazol-4-one ring structure was calculated to have a slightly better energy than the oxazolone, but the barrier to its formation is higher and there was no evidence of this ion in the IRMPD spectrum. By contrast, the a 4 * and [a 4 – H2O]+ (denoted a 4 0) ions from G5 gave strikingly similar IRMPD spectra and both have the 3,5-dihydro-4H-imidazol-4-one ring structure similar to that recently reported for the [GGGG + H – H2O]+ ion [Int. J. Mass Spectrom. 316–318, 268–272 (2012)]. In the absence of a solvent molecule, the pathway to the oxazolone is calculated to be lower than those to thermodynamically more stable products, the a 4 0 and the a 4 * with the 3,5-dihydro-4H-imidazol-4-one ring structure. Incorporation of one water molecule is sufficient to reduce the barrier to formation of the a 4 0 of G5 to below that for formation of the oxazolone. On the equivalent potential energy surface for protonated A5 the barrier to formation of the a 4 0 ion is 12.3 kcal mol–1 higher than that for oxazolone formation and the a 4 0 ion is not observed experimentally.

ᅟ

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Scheme 2
Scheme 3

Similar content being viewed by others

References

  1. Mann, M., Hendrickson, R.C., Pandey, A.: Analysis of proteins and proteomes by mass spectrometry. Annu. Rev. Biochem. 70, 437–473 (2001)

    Google Scholar 

  2. Aebersold, R., Goodlett, D.R.: Mass spectrometry in proteomics. Chem. Rev. 101, 269–295 (2001)

    Article  CAS  Google Scholar 

  3. Savitski, M.M., Kjeldsen, F., Nielsen, M.L., Garbuzynskiy, S.O., Galzitskaya, O.V., Surin, A.K., Zubarev, R.A.: Backbone carbonyl group basicities are related to gas-phase fragmentation of peptides and protein folding. Angew. Chem., Int. Ed. 46, 1481–1484 (2007)

    Article  CAS  Google Scholar 

  4. Yalcin, T., Khouw, K., Csizmadia, I.G., Peterson, M.R., Harrison, A.G.: Why are b ions stable species in peptide spectra? J. Am. Soc. Mass Spectrom. 6, 1165–1174 (1995)

    Article  CAS  Google Scholar 

  5. Paizs, B., Suhai, S.: Fragmentation pathways of protonated peptides. Mass Spectrom. Rev. 24, 508–548 (2005)

    Article  CAS  Google Scholar 

  6. Harrison, A.G.: To b or not to b: the ongoing saga of peptide b ions. Mass Spectrom. Rev. 28, 640–654 (2009)

    Article  CAS  Google Scholar 

  7. Polfer, N.C., Oomens, J., Suhai, S., Paizs, B.: Spectroscopic and theoretical evidence for oxazolone ring formation in collison-induced dissociation of peptides. J. Am. Chem. Soc. 127, 17154–17155 (2005)

    Article  CAS  Google Scholar 

  8. Chen, X.A., Steill, J.D., Oomens, J., Polfer, N.C.: Oxazolone versus macrocycle structures for leu-enkephalin b2–b4: insights from infrared multiple-photon dissociation spectroscopy and gas-phase hydrogen/deuterium exchange. J. Am. Soc. Mass Spectrom. 21, 1313–1321 (2010)

    Article  CAS  Google Scholar 

  9. Polfer, N.C., Oomens, J., Suhai, S., Paizs, B.: Infrared spectroscopy and theoretical studies on gas-phase protonated leu-enkephalin and its fragments: direct experimental evidence for the mobile proton. J. Am. Chem. Soc. 129, 5887–5897 (2007)

    Article  CAS  Google Scholar 

  10. Chen, X., Yu, L., Steill, J.D., Oomens, J., Polfer, N.C.: Effect of peptide fragment size on the propensity of cyclization in collision-induced dissociation: oligoglycine b2–b8. J. Am. Chem. Soc. 131, 18272–18282 (2009)

    Article  CAS  Google Scholar 

  11. Erlekam, U., Bythell, B.J., Scuderi, D., Van Stipdonk, M., Paizs, B., Maitre, P.: Infrared spectroscopy of fragments of protonated peptides: direct evidence for macrocyclic structures of b5 ions. J. Am. Chem. Soc. 131, 11503–11508 (2009)

    Article  CAS  Google Scholar 

  12. Saminathan, I.S., Wang, X.S., Guo, Y.Z., Krakovska, O., Voisin, S., Hopkinson, A.C., Siu, K.W.M.: The extent and effects of peptide sequence scrambling via formation of macrocyclic b ions in model proteins. J. Am. Soc. Mass Spectrom. 21, 2085–2094 (2010)

    Article  CAS  Google Scholar 

  13. Golobrodko, A., Gorshko, M., Good, D., Zubarev, R.: Sequence scrambling in shotgun proteomics is negligible. J. Am. Soc. Mass Spectrom. 22, 1121–1124 (2011)

    Article  Google Scholar 

  14. Yu, L., Tan, Y.L., Tsai, Y., Goodlett, D.R., Polfer, N.C.: On the relevance of peptide sequence permutations in shotgun proteomics studies. J. Proteome Res. 10, 2409–2416 (2011)

    Article  CAS  Google Scholar 

  15. Yoon, S.H., Chamot-Rooke, J., Perkins, B.R., Hilderbrand, A.E., Poutsma, J.C., Wysocki, V.H.: IRMPD spectroscopy shows that AGG forms an oxazolone b 2 + ion. J. Am. Chem. Soc. 130, 17644–17645 (2008)

    Article  CAS  Google Scholar 

  16. Oomens, J., Young, S., Molesworth, S., Van Stipdonk, M.: Spectroscopic evidence for an oxazolone structure of the b 2 fragment ion from protonated trialanine. J. Am. Soc. Mass Spectrom. 20, 334–339 (2009)

    Article  CAS  Google Scholar 

  17. Yalcin, T., Harrison, A.G.: Ion chemistry of protonated lysine derivatives. J. Mass Spectrom. 31, 1237–1243 (1996)

    Article  CAS  Google Scholar 

  18. Farrugia, J.M., Taverner, T., O’Hair, R.A.J.: Side-chain involvement in the fragmentation reactions of protonated methyl esters of histidine and its peptides. Int. J. Mass Spectrom. 209, 99–112 (2001)

    Article  CAS  Google Scholar 

  19. Tsaprailis, G., Nair, H., Zhong, W., Kuppannan, K., Futrell, J.H., Wysocki, V.H.: A mechanistic investigation of the enhanced cleavage at histidine in the gas-phase dissociation of protonated peptides. Anal. Chem. 76, 2083–2094 (2004)

    Article  CAS  Google Scholar 

  20. Bythell, B.J., Csonka, I.P., Suhai, S., Barofsky, D.F., Paizs, B.: Gas-phase structure and fragmentation pathways of singly protonated peptides with N-terminal arginine. J. Phys. Chem. B 114, 15092–15105 (2010)

    Article  CAS  Google Scholar 

  21. Paizs, B., Szlávik, Z., Lendvay, G., Vékey, K., Suhai, S.: Formation of a 2 + ions of protonated peptides. An ab initio study. Rapid Commun. Mass Spectrom. 14, 746–755 (2000)

    Article  CAS  Google Scholar 

  22. Vachet, R.W., Ray, K.L., Glish, G.L.: Origin of product ions in the MS/MS spectra of peptides in a quadrupole ion trap. J. Am. Soc. Mass Spectrom. 9, 341–344 (1998)

    Article  CAS  Google Scholar 

  23. Ambihapathy, K., Yalcin, T., Leung, H.-W., Harrison, A.G.: Pathways to immonium ions in the fragmentation of protonated peptides. J. Mass Spectrom. 32, 209–215 (1997)

    Article  CAS  Google Scholar 

  24. El Aribi, H., Rodriquez, C.F., Almeida, D.R.P., Ling, Y., Mak, W.W.-N., Hopkinson, A.C., Siu, K.W.M.: Elucidation of fragmentation mechanisms of protonated peptide ions and their products: a case study on glycylglycylglycine using density functional theory and threshold collision-induced dissociation. J. Am. Chem. Soc. 125, 9229–9236 (2003)

    Article  Google Scholar 

  25. Verkerk, U.H., Siu, C.-K., Steill, J.D., Aribi, H.E., Zhao, J., Rodriquez, C.F., Oomens, J., Hopkinson, A.C., Siu, K.W.M.: a2 ion derived from triglycine: an N1-protonated 4-imidazolidinone. J. Phys. Chem. Lett. 1, 868–872 (2010)

    Article  CAS  Google Scholar 

  26. Bythell, B.J., Maitre, P., Paizs, B.: Cyclization and rearrangement reactions of a n fragment ions of protonated peptides. J. Am. Chem. Soc. 132, 14766–14779 (2010)

    Article  CAS  Google Scholar 

  27. Verkerk, U.H., Zhao, J., Lau, K.-C., Lam, T.-W., Hao, Q., Steill, J.D., Siu, C.-K., Oomens, J., Hopkinson, A.C., Siu, K.W.M.: Structures of the a 2 ions of Ala-Ala-Ala and Phe-Phe-Phe. Int. J. Mass Spectrom. 330/332, 254–261 (2012)

    Article  Google Scholar 

  28. Bythell, B.J., Hernandez, O., Steinmetz, V., Paizs, B., Maitre, P.: Tyrosine side-chain catalyzed proton transfer in the YG a 2 ion revealed by theory and IR spectroscopy in the ‘fingerprint’ and X-H (X = C, N, O) stretching regions. Int. J. Mass Spectrom. 316/318, 227–234 (2012)

    Article  Google Scholar 

  29. Yalcin, T., Csizmadia, I.G., Peterson, M.R., Harrison, A.G.: The structure and fragmentation of b n (n > 3) ions in peptide spectra. J. Am. Soc. Mass Spectrom. 7, 233–242 (1996)

    Article  CAS  Google Scholar 

  30. Harrison, A.G., Young, A.B.: Fragmentation of protonated oligoalanines: amide bond cleavage and beyond. J. Am. Soc. Mass Spectrom. 15, 1810–1819 (2004)

    Article  CAS  Google Scholar 

  31. Allen, J.M., Racine, A.H., Berman, A.M., Johnson, J.S., Bythell, B.J., Paizs, B., Glish, G.L.: Why are a 3 ions rarely observed? J. Am. Soc. Mass Spectrom. 19, 1764–1770 (2008)

    Article  CAS  Google Scholar 

  32. Vachet, R.W., Bishop, B.M., Erickson, B.W., Glish, G.L.: Novel peptide dissociation: gas-phase intramolecular rearrangement of internal amino acid residues. J. Am. Chem. Soc. 119, 5481–5488 (1997)

    Article  CAS  Google Scholar 

  33. Cooper, T., Talaty, E., Grove, J., Stipdonk, M., Suhai, S., Paizs, B.: Isotope labeling and theoretical study of the formation of a 3 * ions from protonated tetraglycine. J. Am. Soc. Mass Spectrom. 17, 1654–1664 (2006)

    Article  CAS  Google Scholar 

  34. Bythell, B.J., Molesworth, S., Osburn, S., Cooper, T., Paizs, B., Van Stipdonk, M.: Structure and reactivity of a n and a n * peptide fragments investigated using isotope labeling, tandem mass spectrometry, and density functional theory calculations. J. Am. Soc. Mass Spectrom. 19, 1788–1798 (2008)

    Article  CAS  Google Scholar 

  35. Polfer, N.C., Oomens, J.: Reaction products in mass spectrometry elucidated with infrared spectroscopy. Phys. Chem. Chem. Phys. 9, 3804–3817 (2007)

    Article  CAS  Google Scholar 

  36. Marshall, A.G., Wang, T.C.L., Ricca, T.L.: Tailored excitation for Fourier-transform ion-cyclotron resonance mass spectrometry. J. Am. Chem. Soc. 107, 7893–7897 (1985)

    Article  CAS  Google Scholar 

  37. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R., Montgomery, Jr., J. A., 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., Bakken, V., 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., and Pople, J. A., Gaussian, Inc., Wallingford CT.: Gaussian 03, revision D.01. Gaussian Inc., Wallingford CT (2004)

  38. Becke, A.D.: Density functional theory thermochemistry. III. The role of exact exchange. J. Chem. Phys. 98, 5648–5652 (1993)

    Article  CAS  Google Scholar 

  39. Becke, A.D.: A new mixing of Hartree-Fock and local density functional theories. J. Chem. Phys. 98, 1372–1377 (1993)

    Article  CAS  Google Scholar 

  40. Lee, C.T., Yang, W.T., Parr, R.G.: Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys. Rev. B: Condens. Matter 37, 785–789 (1998)

    Article  Google Scholar 

  41. Hehre, W.J., Ditchfield, R., Pople, J.A.: Self-consistent molecular orbital methods: XII. Further extension of Gaussian basis sets for use in molecular orbital studies of organic molecules. J. Chem. Phys. 56, 2257–2261 (1972)

    Article  CAS  Google Scholar 

  42. Hariharan, P.C., Pople, J.A.: The effect of d-functions on molecular orbital energies for hydrocarbons. Chem. Phys. Lett. 16, 217–219 (1972)

    Article  CAS  Google Scholar 

  43. Chandrasekhar, J., Andrade, J.G., Schleyer, P.R.: Efficient and accurate calculation of anion proton affinities. J. Am. Chem. Soc. 103, 5609–5612 (1981)

    Article  CAS  Google Scholar 

  44. Gonzalez, C., Schlegel, H.B.: An improved algorithm for reaction path following. J. Chem. Phys. 90, 2154–2161 (1989)

    Article  CAS  Google Scholar 

  45. Steill, J., Zhao, J., Siu, C.-K., Ke, Y., Verkerk, U.H., Oomens, J., Dunbar, R.C., Hopkinson, A.C., Siu, K.W.M.: Structure of the observable histidine radical cation in the gas phase: a captodative α-radical ion. Angew. Chem. 47, 9666–9668 (2008)

    Article  Google Scholar 

  46. Prell, J.S., Chang, T.M., Biles, J.A., Berden, G., Oomens, J., Williams, E.R.: Isomer population analysis of gaseous ions from infrared multiple photon dissociation kinetics. J. Phys. Chem. A 115, 2745–2751 (2011)

    Article  CAS  Google Scholar 

  47. Verkerk, U.H., Zhao, J., Van Stipdonk, M.J., Bythell, B.J., Oomens, J., Hopkinson, A.C., Siu, K.W.M.: Structure of the [M + H – H2O]+ ion from tetraglycine: a revisit by means of density functional theory and isotope labeling. J. Phys. Chem. A 115, 6683–6687 (2011)

    Article  CAS  Google Scholar 

  48. Lau, J.K.-C., Zhao, J., Siu, K.W.M., Hopkinson, A.C.: Elimination of water from the backbone of protonated tetraglycine. Inter. J. Mass Spectrom 316-318, 268–272 (2012)

    Article  CAS  Google Scholar 

  49. Prell, J.S., O’Brien, J.T., Steill, J.D., Oomens, J., Williams, E.R.: Structures of protonated dipeptides: the role of arginine in stabilizing salt bridges. J. Am. Chem. Soc. 131, 11442–11449 (2009)

    Article  CAS  Google Scholar 

  50. Forbes, M.W., Bush, M.F., Polfer, N.C., Oomens, J., Dunbar, R.C., Williams, E.R., Jockusch, R.A.: Infrared spectroscopy of arginine cation complexes: direct observation of gas-phase zwitterions. J. Phys. Chem. A 111, 11759–11770 (2007)

    Article  CAS  Google Scholar 

  51. O’Brien, J.T., Prell, J.S., Steill, J.D., Oomens, J., Williams, E.R.: Interactions of mono- and divalent metal ions with aspartic and glutamic acid investigated with IR photodissociation spectroscopy and theory. J. Phys. Chem. A 112, 10823–10830 (2008)

    Article  Google Scholar 

  52. Prell, J.S., Demireva, M., Williams, E.R.: Role of sequence in salt-bridge formation for alkali metal cationized GlyArg and ArgGly investigated with IRMPD spectroscopy and theory. J. Am. Chem. Soc. 131, 1232–1242 (2009)

    Article  CAS  Google Scholar 

  53. Polfer, N.C., Oomens, J., Dunbar, R.C.: Alkali metal complexes of the dipeptides PheAla and AlaPhe: IRMPD Spectroscopy. Chem. Phys. Chem. 9, 579–589 (2008)

    Article  CAS  Google Scholar 

  54. Paizs, B., Bythell, B.J., Maitre, P.: Rearrangement pathways of the a 4 ion of protonated YGGFL characterized by ir spectroscopy and modeling. J. Am. Soc. Mass Spectrom. 23, 664–675 (2012)

    Article  CAS  Google Scholar 

  55. Bender, M.L.: Oxygen exchange as evidence for the existence of an intermediate in ester hydrolysis. J. Am. Chem. Soc. 73, 1626–1629 (1951)

    Article  CAS  Google Scholar 

  56. Bender, M.L.: Intermediates in the reactions of carboxylic acid derivatives. II. Infrared absorption spectra as evidence for the formation of addition compounds of carboxylic acid derivatives. J. Am. Chem. Soc. 75, 5986–5990 (1953)

    Article  CAS  Google Scholar 

  57. Dsouza, V.T., Bender, M.L.: Miniature organic models of enzymes. Acc. Chem. Res. 20, 146–152 (1987)

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors acknowledge support for this study by the Natural Sciences and Engineering Research Council (NSERC) of Canada and made possible by the facilities of the Shared Hierarchical Academic Research Computing Network (http://www.sharcnet.ca) and the High Performance Computing Virtual Laboratory (http://www.hpcvl.org). Skillful assistance of the FELIX staff is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Department of Chemistry and Centre for Research in Mass Spectrometry, York University, Toronto, ON, M3J 1P3, Canada

    Junfang Zhao, Justin Kai-Chi Lau, Udo H. Verkerk, K. W. Michael Siu & Alan C. Hopkinson

  2. FOM Institute for Plasma Physics, University of Amsterdam, 3430 BE Nieuwegein, 1018WV, Amsterdam, The Netherlands

    Josipa Grzetic & Jos Oomens

Authors
  1. Junfang Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Justin Kai-Chi Lau
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Josipa Grzetic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Udo H. Verkerk
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jos Oomens
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K. W. Michael Siu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alan C. Hopkinson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alan C. Hopkinson.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

Schematic diagrams showing the formation of VII from XVII, the displacement of NH3 from the C-terminal protonated imine-amide by water creating the COOH group prior to formation of the five-membered ring, , the fragmentation of structures VII and VIII, the % parent ion depletion for Figures 1, 3, 4, 5 and 6, the CID spectrum of a 4 ion derived from G 5 , structure V diastereomer formation, the full reference for Gaussian 03, Revision D, and total energies and Cartesian coordinates of the optimized structures at the B3LYP/6-311++G(d,p) level of theory. (PDF 554 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhao, J., Lau, J.KC., Grzetic, J. et al. Structures of a n * Ions Derived from Protonated Pentaglycine and Pentaalanine: Results from IRMPD Spectroscopy and DFT Calculations. J. Am. Soc. Mass Spectrom. 24, 1957–1968 (2013). https://doi.org/10.1007/s13361-013-0728-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13361-013-0728-4

Key words

Search

Navigation