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Integration of High-Resolution Mass Spectrometry with Cryogenic Ion Vibrational Spectroscopy

  • Fabian S. Menges
  • Evan H. Perez
  • Sean C. Edington
  • Chinh H. Duong
  • Nan Yang
  • Mark A. JohnsonEmail author
Research Article

Abstract

We describe an instrumental configuration for the structural characterization of fragment ions generated by collisional dissociation of peptide ions in the typical MS2 scheme widely used for peptide sequencing. Structures are determined by comparing the vibrational band patterns displayed by cryogenically cooled ions with calculated spectra for candidate structural isomers. These spectra were obtained in a linear action mode by photodissociation of weakly bound D2 molecules. This is accomplished by interfacing a Thermo Fisher Scientific Orbitrap Velos Pro to a cryogenic, triple focusing time-of-flight photofragmentation mass spectrometer (the Yale TOF spectrometer). The interface involves replacement of the Orbitrap’s higher-energy collisional dissociation cell with a voltage-gated aperture that maintains the commercial instrument’s standard capabilities while enabling bidirectional transfer of ions between the high-resolution FT analyzer and external ion sources. The performance of this hybrid instrument is demonstrated by its application to the a1, y1 and z1 fragment ions generated by CID of a prototypical dipeptide precursor, protonated L-phenylalanyl-L-tyrosine (H+-Phe-Tyr-OH or FY-H+). The structure of the unusual z1 ion, nominally formed after NH3 is ejected from the protonated tyrosine (y1) product, is identified as the cyclopropane-based product is tentatively identified as a cyclopropane-based product.

Keywords

Cryogenic vibrational spectroscopy MS2 Peptide ion fragment structure Orbitrap High-resolution mass spectrometry 

Notes

Acknowledgements

MAJ thanks the Air Force Office of Scientific Research (AFOSR) under grants FA9550-17-1-0267 (DURIP) and FA9550-18-1-0213. CHD thanks the National Science Foundation Graduate Research Fellowship for funding under Grant No. DGE-1122492. FSM thanks Prof. David Russell and Michael Poltash (Texas A&M) for useful discussions about their adaptation of a Thermo Fisher Scientific Exactive Plus in combination with an external ion source and Henk Terink from Thermo Fisher Scientific for technical support. EHP thanks the support of the National Institute of Health for the stipend supported under the Biophysical Training Grant 2T32GM008283-31.

Supplementary material

13361_2019_2238_MOESM1_ESM.pdf (2.4 mb)
ESM 1 (PDF 2475 kb)

References

  1. 1.
    Wolk, A.B., Leavitt, C.M., Garand, E., Johnson, M.A.: Cryogenic ion chemistry and spectroscopy. Acc. Chem. Res. 47, 202–210 (2014)CrossRefGoogle Scholar
  2. 2.
    Kamrath, M.Z., Rizzo, T.R.: Combining ion mobility and cryogenic spectroscopy for structural and analytical studies of biomolecular ions. Acc. Chem. Res. 51, 1487–1495 (2018)CrossRefGoogle Scholar
  3. 3.
    Rizzo, T.R., Boyarkin, O.V.: Cryogenic methods for the spectroscopy of large, biomolecular ions. Gas-Phase Ir Spectroscopy and Structure of Biological Molecules Top. Curr. Chem, 364, 43-98 (2015)Google Scholar
  4. 4.
    Rizzo, T.R., Stearns, J.A., Boyarkin, O.V., et al.: Int. Rev. Phys. Chem. 28, 481–515 (2009)CrossRefGoogle Scholar
  5. 5.
    Boyarkin, O.V.: Cold ion spectroscopy for structural identifications of biomolecules. Int. Rev. Phys. Chem. 37, 559–606 (2018)CrossRefGoogle Scholar
  6. 6.
    Polfer, N.C., Paizs, B., Snoek, L.C., Compagnon, I., Suhai, S., Meijer, G., et al.: Infrared fingerprint spectroscopy and theoretical studies of potassium ion tagged amino acids and peptides in the gas phase. J. Am. Chem. Soc. 123, 8571 (2005)CrossRefGoogle Scholar
  7. 7.
    Roithová, J., Gray, A., Andris, E., Jašík, J., Gerlich, D.: Helium tagging infrared photodissociation spectroscopy of reactive ions. Acc. Chem. Res. 49, 223–230 (2016)CrossRefGoogle Scholar
  8. 8.
    Li, J.-W., Morita, M., Takahashi, K., Kuo, J.-L.: Features in vibrational spectra induced by Ar-tagging for H3O+Arm, m = 0–3. J. Phys. Chem. A. 119, 10887–10892 (2015)CrossRefGoogle Scholar
  9. 9.
    Brummer, M., Kaposta, C., Santambrogio, G., Asmis, K.R.: Formation and photodepletion of cluster ion-messenger atom complexes in a cold ion trap: infrared spectroscopy of VO+, VO2 +, and VO3. J. Chem. Phys. 119, 12700–12703 (2003)CrossRefGoogle Scholar
  10. 10.
    Duong, C.H., Yang, N., Kelleher, P.J., Johnson, M.A., DiRisio, R.J., McCoy, A.B., et al.: Tag-free and isotopomer-selective vibrational spectroscopy of the cryogenically cooled H9O4 + cation with two-color, IR-IR double-resonance photoexcitation: isolating the spectral signature of a single OH group in the hydronium ion core. J. Phys. Chem. A. 122, 9275–9284 (2018)CrossRefGoogle Scholar
  11. 11.
    Yang, N., Duong, C.H., Kelleher, P.J., Johnson, M.A., McCoy, A.B.: Isolation of site-specific anharmonicities of individual water molecules in the I¯·(H2O)2 complex using tag-free, Isotopomer Selective IR-IR Double Resonance. Chem. Phys. Lett. 690, 159–171 (2017)CrossRefGoogle Scholar
  12. 12.
    Heine, N., Yacovitch, T.I., Schubert, F., Brieger, C., Neumark, D.M., Asmis, K.R.: Infrared photodissociation spectroscopy of microhydrated nitrate-nitric acid clusters NO3¯(HNO3)m(H2O)n. J. Phys. Chem. A. 118, 7613–7622 (2014)CrossRefGoogle Scholar
  13. 13.
    Nagornova, N.S., Rizzo, T.R., Boyarkin, O.V.: Interplay of intra- and intermolecular H-bonding in a progressively solvated macrocyclic peptide. Science. 336, 320–323 (2012)CrossRefGoogle Scholar
  14. 14.
    Chakrabarty, S., Holz, M., Campbell, E.K., Banerjee, A., Gerlich, D., Maier, J.P.: A novel method to measure electronic spectra of cold molecular ions. J. Phys. Chem. Lett. 4, 4051–4054 (2013)CrossRefGoogle Scholar
  15. 15.
    Schmies, M., Patzer, A., Schutz, M., Miyazaki, M., Fujii, M., Dopfer, O.: Microsolvation of the acetanilide cation (AA+) in a nonpolar solvent: IR spectra of AA+-Ln clusters (L = He, Ar, N2; n <= 10). Phys. Chem. Chem. Phys. 16, 7980–7995 (2014)CrossRefGoogle Scholar
  16. 16.
    Liu, H.T., Ning, C.G., Huang, D.L., Wang, L.S.: Vibrational spectroscopy of the dehydrogenated uracil radical by autodetachment of dipole-bound excited states of cold anions. Angew. Chem. Int. Edit. 53, 2464–2468 (2014)CrossRefGoogle Scholar
  17. 17.
    Wolke, C.T., Fournier, J.A., Dzugan, L.C., Fagiani, M.R., Odbadrakh, T.T., Knorke, H., et al.: Spectroscopic snapshots of the proton-transfer mechanism in water. Science. 354, 1131–1135 (2016)CrossRefGoogle Scholar
  18. 18.
    Duffy, E.M., Voss, J.M., Garand, E.: Vibrational characterization of microsolvated electrocatalytic water oxidation intermediate: [Ru(tpy)(bpy)(OH)]2+(H2O)0-4. J. Phys. Chem. A. 121, 5468–5474 (2017)CrossRefGoogle Scholar
  19. 19.
    Redwine, J.G., Davis, Z.A., Burke, N.L., Oglesbee, R.A., McLuckey, S.A., Zwier, T.S.: A novel ion trap based tandem mass spectrometer for the spectroscopic study of cold gas phase polyatomic ions. Int. J. Mass Spectrom. 348, 9–14 (2013)CrossRefGoogle Scholar
  20. 20.
    Feraud, G., Dedonder, C., Jouvet, C., Inokuchi, Y., Haino, T., Sekiya, R., et al.: Development of ultraviolet-ultraviolet hole-burning spectroscopy for cold gas-phase ions. J. Phys. Chem. Lett. 5, 1236–1240 (2014)CrossRefGoogle Scholar
  21. 21.
    Svendsen, A., Lorenz, U.J., Boyarkin, O.V., Rizzo, T.R.: A new tandem mass spectrometer for photofragment spectroscopy of cold, Gas-Phase Molecular Ions. Rev. Sci. Instrum. 81, 073107 (2010)CrossRefGoogle Scholar
  22. 22.
    Heine, N., Asmis, K.R.: Cryogenic ion trap vibrational spectroscopy of hydrogen-bonded clusters relevant to atmospheric chemistry. Int. Rev. Phys. Chem. 34, 1–34 (2015)CrossRefGoogle Scholar
  23. 23.
    Kamrath, M.Z., Garand, E., Jordan, P.A., Leavitt, C.M., Wolk, A.B., Van Stipdonk, M.J., et al.: Vibrational characterization of simple peptides using cryogenic infrared photodissociation of H2-tagged, Mass-Selected Ions. J. Am. Chem. Soc. 133, 6440–6448 (2011)CrossRefGoogle Scholar
  24. 24.
    Marsh, B.M., Voss, J.M., Garand, E.: A dual cryogenic ion trap spectrometer for the formation and characterization of solvated ionic clusters. J. Chem. Phys. 143, 204201 (2015)CrossRefGoogle Scholar
  25. 25.
    Kopysov, V., Makarov, A., Boyarkin, O.V.: Colors for molecular masses: fusion of spectroscopy and mass spectrometry for identification of biomolecules. Anal. Chem. 87, 4607–4611 (2015)CrossRefGoogle Scholar
  26. 26.
    Poltash, M.L., McCabe, J.W., Shirzadeh, M., Laganowsky, A., Clowers, B.H., Russell, D.H.: Fourier transform-ion mobility-Orbitrap mass spectrometer: a next-generation instrument for native mass spectrometry. Anal. Chem. 90, 10472–10478 (2018)CrossRefGoogle Scholar
  27. 27.
    Reinhard, B.M., Lagutschenkov, A., Lemaire, J., Maitre, P., Boissel, P., Niedner-Schatteburg, G.: Reductive nitrile coupling in niobium-acetonitrile complexes probed by free electron laser IR multiphoton dissociation spectroscopy. J. Phys. Chem. A. 108, 3350–3355 (2004)CrossRefGoogle Scholar
  28. 28.
    James, P.: Protein identification in the post-genome era: the rapid rise of proteomics. Q. Rev. Biophys. 30, 279–331 (1997)CrossRefGoogle Scholar
  29. 29.
    Roepstorff, P., Fohlman, J.: Proposal for a common nomenclature for sequence ions in mass-spectra of peptides. Biomed. Mass Spectrom. 11, 601–601 (1984)CrossRefGoogle Scholar
  30. 30.
    Dettmer, K., Aronov, P.A., Hammock, B.D.: Mass spectrometry-based metabolomics. Mass Spectrom. Rev. 26, 51–78 (2007)CrossRefGoogle Scholar
  31. 31.
    Martens, J., Grzetic, J., Berden, G., Oomens, J.: Structural identification of electron transfer dissociation products in mass spectrometry using infrared ion spectroscopy. Nat. Commun. 7, 11754 (2016)CrossRefGoogle Scholar
  32. 32.
    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)CrossRefGoogle Scholar
  33. 33.
    Bythell, B.J., Dain, R.P., Curtice, S.S., Oomens, J., Steill, J.D., Groenewold, G.S., et al.: Structure of [M+H-H2O]+ from protonated tetraglycine revealed by tandem mass spectrometry and IRMPD spectroscopy. J. Phys. Chem. A. 114, 5076–5082 (2010)Google Scholar
  34. 34.
    Pittman, J.L., O'Connor, P.B.: A minimum thickness gate valve with integrated ion optics for mass spectrometry. J. Am. Soc. Mass Spectrom. 16, 441–445 (2005)CrossRefGoogle Scholar
  35. 35.
    Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., et al.: Gaussian 09, Revision D.01. (2009)Google Scholar
  36. 36.
    Stearns, J.A., Mercier, S., Seaiby, C., Guidi, M., Boyarkin, O.V., Rizzo, T.R.: Conformation-specific spectroscopy and photodissociation of cold, protonated tyrosine and phenylalanine. J. Am. Chem. Soc. 129, 11814–11820 (2007)CrossRefGoogle Scholar
  37. 37.
    Masellis, C., Khanal, N., Kamrath, M.Z., Clemmer, D.E., Rizzo, T.R.: Cryogenic vibrational spectroscopy provides unique fingerprints for glycan identification. J. Am. Soc. Mass Spectrom. 28, 2217–2222 (2017)CrossRefGoogle Scholar
  38. 38.
    Mucha, E., González Flórez, A.I., Marianski, M., Thomas, D.A., Hoffmann, W., Struwe, W.B., et al.: Glycan fingerprinting via cold-ion infrared spectroscopy. Angew. Chem. Int. Ed. 56, 11248–11251 (2017)CrossRefGoogle Scholar
  39. 39.
    Lioe, H., O'Hair, R.A.J.: Comparison of collision-induced dissociation and electron-induced dissociation of singly protonated aromatic amino acids, cystine and related simple peptides using a hybrid linear ion trap-FT-ICR mass spectrometer. Anal. Bioanal. Chem. 389, 1429–1437 (2007)CrossRefGoogle Scholar
  40. 40.
    Scott, N.E., Parker, B.L., Connolly, A.M., Paulech, J., Edwards, A.V.G., Crossett, B., et al.: Simultaneous glycan-peptide characterization using hydrophilic interaction chromatography and parallel fragmentation by CID, higher energy collisional dissociation, and electron transfer dissociation MS applied to the N-linked glycoproteome of campylobacter jejuni. Mol. Cell. Proteomics. 10, M000031–MMCP201 (2011)CrossRefGoogle Scholar
  41. 41.
    Falick, A.M., Hines, W.M., Medzihradszky, K.F., Baldwin, M.A., Gibson, B.W.: Low-mass ions produced from peptides by high-energy collision-induced dissociation in tandem mass-spectrometry. J. Am. Soc. Mass Spectrom. 4, 882–893 (1993)CrossRefGoogle Scholar
  42. 42.
    Dass, C.: Fundamentals of contemporary mass spectrometry. John Wiley & Sons (2007)Google Scholar

Copyright information

© American Society for Mass Spectrometry 2019

Authors and Affiliations

  1. 1.Department of ChemistryYale UniversityNew HavenUSA

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