Journal of The American Society for Mass Spectrometry

, Volume 29, Issue 9, pp 1791–1801 | Cite as

Radical Rearrangement Chemistry in Ultraviolet Photodissociation of Iodotyrosine Systems: Insights from Metastable Dissociation, Infrared Ion Spectroscopy, and Reaction Pathway Calculations

  • Karnamohit Ranka
  • Ning Zhao
  • Long Yu
  • John F. Stanton
  • Nicolas C. PolferEmail author
Focus: Application of Photons and Radicals for MS: Research Article


We report on the ultraviolet photodissociation (UVPD) chemistry of protonated tyrosine, iodotyrosine, and diiodotyrosine. Distonic loss of the iodine creates a high-energy radical at the aromatic ring that engages in hydrogen/proton rearrangement chemistry. Based on UVPD kinetics measurements, the appearance of this radical is coincident with the UV irradiation pulse (8 ns). Conversely, sequential UVPD product ions exhibit metastable decay on ca. 100 ns timescales. Infrared ion spectroscopy is capable of confirming putative structures of the rearrangement products as proton transfers from the imine and β-carbon hydrogens. Potential energy surfaces for the various reaction pathways indicate that the rearrangement chemistry is highly complex, compatible with a cascade of rearrangements, and that there is no preferred rearrangement pathway even in small molecular systems like these.

Graphical Abstract


UVPD Kinetics IRMPD spectroscopy DFT Metastable decay 


Funding Information

The project was financially supported by the United States National Science Foundation (NSF) under grant number CHE-1403262.

Supplementary material

13361_2018_1959_MOESM1_ESM.pdf (2.1 mb)
ESM 1 (PDF 2141 kb)


  1. 1.
    Turecek, F., Julian, R.R.: Peptide radicals and cation radicals in the gas phase. Chem. Rev. 113, 6691–6733 (2013)CrossRefPubMedGoogle Scholar
  2. 2.
    Zubarev, R.A., Kelleher, N.L., McLafferty, F.W.: Electron capture dissociation of multiply charged protein cations. A nonergodic process. J. Am. Chem. Soc. 120, 3265–3266 (1998)CrossRefGoogle Scholar
  3. 3.
    Mirgorodskaya, E., Roepstorff, P., Zubarev, R.A.: Localization of O-glycosylation sites in peptides by electron capture dissociation in a Fourier transform mass spectrometer. Anal. Chem. 71(20), 4431–4436 (1999)CrossRefPubMedGoogle Scholar
  4. 4.
    Syka, J.E.P., Coon, J.J., Schroeder, M.J., Shabanowitz, J., Hunt, D.F.: Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry. Proc. Natl. Acad. Sci. U. S. A. 101, 9528–9533 (2004)CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Mikesh, L., Ueberheide, B., Chi, A., Coon, J., Syka, J.E.P., Shabanowitz, J., Hunt, D.F.: The utility of ETD mass spectrometry in proteomic analysis. Biochim. Biophys. Acta - Prot. Proteom. 1764, 1811–1822 (2006)CrossRefGoogle Scholar
  6. 6.
    Robinson, M.R., Moore, K.L., Brodbelt, J.S.: Direct identification of tyrosine sulfation by using ultraviolet photodissociation mass spectrometry. J. Am. Soc. Mass Spectrom. 25, 1461–1471 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Parthasarathi, R., He, Y., Reilly, J., Raghavachari, K.: New insights into the vacuum UV photodissociation of peptides. J. Am. Chem. Soc. 132, 1606–1610 (2010)CrossRefPubMedGoogle Scholar
  8. 8.
    Ly, T., Julian, R.R.: Residue-specific radical-directed dissociation of whole proteins in the gas phase. J. Am. Chem. Soc. 130, 351–358 (2008)CrossRefPubMedGoogle Scholar
  9. 9.
    Ly, T., Julian, R.R.: Elucidating the tertiary structure of protein ions in vacuo with site specific photoinitiated radical reactions. J. Am. Chem. Soc. 132, 8602–8609 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Brodbelt, J.S.: Photodissociation mass spectrometry: new tools for characterization of biological molecules. Chem. Soc. Rev. 43, 2757–2783 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Fung, Y., Kjeldsen, F., Silivra, O., Chan, T., Zubarev, R.A.: Facile disulfide bond cleavage in gaseous peptide and protein cations by ultraviolet photodissociation at 157 nm. Angew. Chem. Int. Ed. Engl. 44, 6399–6403 (2005)CrossRefPubMedGoogle Scholar
  12. 12.
    Hunt, D.F., Shabanowitz, J., Yates John 3rd, R.: Peptide sequence analysis by laser photodissociation Fourier transform mass spectrometry. J. Chem. Soc. Chem. Commun. 8, 548–550 (1987)CrossRefGoogle Scholar
  13. 13.
    Williams, E.R., Furlong, J.J.P., McLafferty, F.W.: Efficiency of collisionally-activated dissociation and 193-nm photodissociation of peptide ions in Fourier transform mass spectrometry. J. Am. Soc. Mass Spectrom. 1, 288–294 (1990)CrossRefPubMedGoogle Scholar
  14. 14.
    Julian, R.R.: The mechanism behind top-down UVPD experiments: making sense of apparent contradictions. J. Am. Soc. Mass Spectrom. 28, 1823–1826 (2017)CrossRefPubMedCentralGoogle Scholar
  15. 15.
    Syrstad, E.A., Turecek, F.: Toward a general mechanism of electron capture dissociation. J. Am. Soc. Mass Spectrom. 16, 208–224 (2005)CrossRefPubMedGoogle Scholar
  16. 16.
    Sobczyk, M., Anusiewicz, W., Berdys-Kochanska, J., Sawicka, A., Skurski, P., Simons, J.: Coulomb-assisted dissociative electron attachment: application to a model peptide. J. Phys. Chem. A. 109, 250–258 (2005)CrossRefPubMedGoogle Scholar
  17. 17.
    Thoen, K.K., Perez, J., Ferra, J.J., Kenttamaa, H.I.: Synthesis of charged phenyl radicals and biradicals by laser photolysis in a Fourier transform ion cyclotron resonance mass spectrometer. J. Am. Soc. Mass Spectrom. 9, 1135–1140 (1998)CrossRefPubMedGoogle Scholar
  18. 18.
    Gauthier, J.W., Trautman, T.R., Jacobson, D.B.: Sustained off-resonance irradiation for collision-activated dissociation involving Fourier-transform mass-spectrometry—collision-activated dissociation technique that emulates infrared multiphoton dissociation. Anal. Chim. Acta. 246, 211–225 (1991)CrossRefGoogle Scholar
  19. 19.
    Chu, I.K., Rodriguez, C.F., Lau, T.C., Hopkinson, A., Siu, K.: Molecular radical cations of oligopeptides. J. Phys. Chem. B. 104, 3393–3397 (2000)CrossRefGoogle Scholar
  20. 20.
    Hao, G., Gross, S.: Electrospray tandem mass spectrometry analysis of S- and N-nitrosopeptides: facile loss of NO and radical-induced fragmentation. J. Am. Soc. Mass Spectrom. 17, 1725–1730 (2006)CrossRefPubMedGoogle Scholar
  21. 21.
    Gallardo, V.A., Jankiewicz, B.J., Vinueza, N.R., Nash, J.J., Kenttamaa, H.I.: Reactivity of a σ,σ,σ,σ-tetraradical: the 2,4,6-trihydropyridine radical cation. J. Am. Chem. Soc. 134, 1926–1929 (2012)CrossRefPubMedGoogle Scholar
  22. 22.
    Heidbrink, J.L., Ramirez-Arizmendi, L.E., Thoen, K.K., Guler, L., Kenttamaa, H.I.: Polar effects control hydrogen-abstraction reactions of charged, substituted phenyl radicals. J. Phys. Chem. A. 105, 7875–7884 (2001)CrossRefGoogle Scholar
  23. 23.
    Marconi, G.: Model for the photodissociation of aryl halides. J. Photochem. 11, 385–391 (1979)CrossRefGoogle Scholar
  24. 24.
    Polfer, N.: Infrared multiple photon dissociation spectroscopy of trapped ions. Chem. Soc. Rev. 40, 2211–2221 (2011)CrossRefPubMedGoogle Scholar
  25. 25.
    Antoine, R. and P. Dugourd, UV-visible activation of biomolecular ions. In: Polfer, N.C., Dugourd, P. (eds.) Laser Photodissociation and Spectroscopy of Mass-Separated Biomolecular Ions, pp. 93–116. Springer: Lect. Notes Chem., Vol. 83, (2013)Google Scholar
  26. 26.
    Lesslie, M., Lawler, J.T., Dang, A., Korn, J.A., Bim, D., Steinmetz, V., Maitre, P., Turecek, F., Ryzhov, V.: Cytosine radical cations: a gas-phase study combining IRMPD spectroscopy, UVPD spectroscopy, ion-molecule reactions, and theoretical calculations. Chem. Phys. Chem. 18, 1293–1301 (2017)CrossRefPubMedGoogle Scholar
  27. 27.
    Osburn, S., Berden, G., Oomens, J., Gulyuz, K., Polfer, N.C., O'Hair, R.A.J., Ryzhov, V.: Structure and reactivity of the glutathione radical cation: radical rearrangement from the cysteine sulfur to the glutamic acid alpha-carbon atom. Chem. Plus Chem. 78, 970–978 (2013)Google Scholar
  28. 28.
    Brunet, C., Antoine, R., Dugourd, P., Canon, F., Giuliani, A., Nahon, L.: Formation and fragmentation of radical peptide anions: insights from vacuum ultra violet spectroscopy. J. Am. Soc. Mass Spectrom. 23, 274–281 (2012)CrossRefPubMedGoogle Scholar
  29. 29.
    Kirk, B.B., Trevitt, A.J., Blanksby, S.J., Tao, Y.Q., Moore, B.N., Julian, R.R.: Ultraviolet action spectroscopy of iodine labeled peptides and proteins in the gas phase. J. Phys. Chem. A. 117, 1228–1232 (2013)CrossRefPubMedGoogle Scholar
  30. 30.
    Shaffer, S.A., Pepin, R., Turecek, F.: Combining UV photodissociation action spectroscopy with electron transfer dissociation for structure analysis of gas-phase peptide cation-radicals. J. Mass Spectrom. 50, 1438–1442 (2015)CrossRefPubMedGoogle Scholar
  31. 31.
    Bellina, B., Compagnon, I., Houver, S., Maitre, P., Allouche, A.R., Antoine, R., Dugourd, P.: Spectroscopic signatures of peptides containing tryptophan radical cations. Angew. Chem. Int. Ed. Engl. 50, 11430–11432 (2011)CrossRefPubMedGoogle Scholar
  32. 32.
    Gulyuz, K., Stedwell, C.N., Wang, D., Polfer, N.C.: Hybrid quadrupole mass filter/quadrupole ion trap/time-of-flight-mass spectrometer for infrared multiple photon dissociation spectroscopy of mass-selected ions. Rev. Sci. Instrum. 82, 054101 (2011)CrossRefPubMedGoogle Scholar
  33. 33.
    March, R., Londry, F., Alfred, R., Franklin, A., Todd, J.: Mass-selective isolation of ions stored in a quadrupole ion trap—a simulation study. Int. J. Mass Spectrom. Ion Proc. 112, 247–271 (1992)CrossRefGoogle Scholar
  34. 34.
    Polfer, N., Oomens, J.: Vibrational spectroscopy of bare and solvated ions of biological significance. Mass Spectrom. Rev. 28, 468–494 (2009)CrossRefPubMedGoogle Scholar
  35. 35.
    Fridgen, T.D.: Infrared consequence spectroscopy of gaseous protonated and metal ion cationized complexes. Mass Spectrom. Rev. 28, 586–607 (2009)CrossRefPubMedGoogle Scholar
  36. 36.
    Stephens, P.J., Devlin, F.J., Chabalowski, C.F., Frisch, M.J.: Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields: a comparison of local, nonlocal, and hybrid density functional. J. Phys. Chem. 98, 11623–11627 (1994)CrossRefGoogle Scholar
  37. 37.
    Stephens, P.J., Devlin, F.J., Ashvar, C.S., Chabalowski, C.F., Frisch, M.J.: Theoretical calculations of vibrational circular-dichroism spectra. Fara. Disc. 99, 103–119 (1994)CrossRefGoogle Scholar
  38. 38.
    McLean, A.D., Chandler, G.S.: Contracted Gaussian-basis sets for molecular calculations. 1. 2nd row atoms, Z=11–18. J. Chem. Phys. 72, 5639–5648 (1980)CrossRefGoogle Scholar
  39. 39.
    Krichnan, R., Binkley, J.S., Seeger, R., Pople, J.A.: Self-consistent molecular orbital methods. 20. basis set for correlated wave-functions. J. Chem. Phys. 72, 650–654 (1980)CrossRefGoogle Scholar
  40. 40.
    Valiev, M., Bylaska, E.J., Govind, N., Kowalski, K., Straatsma, T.P., Van Dam, H.J.J., Wang, D., Nieplocha, J., Apra, E., Windus, T.L., de Jong, W.A.: NWChem: a comprehensive and scalable open-source solution for large scale molecular simulations. Comp. Phys. Commun. 181, 1477–1489 (2010)CrossRefGoogle Scholar
  41. 41.
    Mino, W.K., Gulyuz, K., Wang, D., Stedwell, C.N., Polfer, N.: Gas-phase structure and dissociation chemistry of protonated tryptophan elucidated by infrared multiple-photon dissociation spectroscopy. J. Phys. Chem. Lett. 2, 299–304 (2011)CrossRefGoogle Scholar
  42. 42.
    Nicely, A.L., Miller, D.J., Lisy, J.M.: Charge and temperature dependence of biomolecule conformations: K+tryptamine-(H2O)n clusters. J. Am. Chem. Soc. 131, 6314–6315 (2009)CrossRefPubMedGoogle Scholar
  43. 43.
    El Aribi, H., Orlova, G., Hopkinson, A., Siu, K.: Gas-phase fragmentation reactions of protonated aromatic amino acids: concomitant and consecutive neutral eliminations and radical cation formations. J. Phys. Chem. A. 108, 3844–3853 (2004)CrossRefGoogle Scholar
  44. 44.
    Blanksby, S.J., Ellison, G.B.: Bond dissociation energies of organic molecules. Acc. Chem. Res. 36, 255–263 (2003)CrossRefPubMedGoogle Scholar
  45. 45.
    O'Hair, R.A.J., Broughton, P.S., Styles, M.L., Frink, B.T., Hadad, C.M.: The fragmentation pathways of protonated glycine: a computational study. J. Am. Soc. Mass Spectrom. 11, 687–696 (2000)CrossRefPubMedGoogle Scholar
  46. 46.
    Laskin, J., Futrell, J.H.: Surface-induced dissociation of peptide ions: kinetics and dynamics. J. Am. Soc. Mass Spectrom. 14, 1340–1347 (2003)CrossRefPubMedGoogle Scholar
  47. 47.
    Weickhardt, C., Lifshitz, C.: Determination of kinetic-energy release distributions by metastable peak shape-analysis in an ion-trap reflectron time-of-flight instrument. Eur. Mass Spectrom. 1, 223–228 (1995)CrossRefGoogle Scholar
  48. 48.
    Pepin, R., Layton, E.D., Liu, Y., Afonso, C., Turecek, F.: Where does the electron go? Stable and metastable peptide cation radicals formed by electron transfer. J. Am. Soc. Mass Spectrom. 28, 164–181 (2017)CrossRefPubMedGoogle Scholar
  49. 49.
    Cheng, P.Y., Zhong, D., Zewail, A.H.: Kinetic-energy, femtosecond resolved reaction dynamics. Modes of dissociation (in iodobenzene) from time-velocity correlations. Chem. Phys. Lett. 237, 399–405 (1995)CrossRefGoogle Scholar
  50. 50.
    Hansen, K., The evaporative ensemble, in Statistical Physics of Nanoparticles in the Gas Phase, Springer: Atomic, Optical, and Plasma Physics, 73, p. 113–146 (2013)Google Scholar
  51. 51.
    Merrick, J.P., Moran, D., Radom, L.: An evaluation of harmonic vibrational frequency scale factors. J. Phys. Chem. A. 111, 11683–11700 (2007)CrossRefPubMedGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2018

Authors and Affiliations

  • Karnamohit Ranka
    • 1
    • 2
  • Ning Zhao
    • 3
  • Long Yu
    • 3
  • John F. Stanton
    • 1
    • 2
  • Nicolas C. Polfer
    • 3
    Email author
  1. 1.Quantum Theory Project, Department of ChemistryUniversity of FloridaGainesvilleUSA
  2. 2.Quantum Theory Project, Department of PhysicsUniversity of FloridaGainesvilleUSA
  3. 3.Department of Chemistry and Center for Chemical PhysicsUniversity of FloridaGainesvilleUSA

Personalised recommendations