Abstract
High power femtosecond laser pulses have unique properties that could lead to their application as ionization or activation sources in mass spectrometry. By concentrating many photons into pulse lengths approaching the timescales associated with atomic motion, very strong electric field strengths are generated, which can efficiently ionize and fragment molecules without the need for resonant absorption. However, the complex interaction between these pulses and biomolecular species is not well understood. To address this issue, we have studied the interaction of intense, femtosecond pulses with a number of amino acids and small peptides. Unlike previous studies, we have used neutral forms of these molecular targets, which allowed us to investigate dissociation of radical cations without the spectra being complicated by the action of mobile protons. We found fragmentation was dominated by fast, radical-initiated dissociation close to the charge site generated by the initial ionization or from subsequent ultrafast migration of this charge. Fragments with lower yields, which are useful for structural determinations, were also observed and attributed to radical migration caused by hydrogen atom transfer within the molecule.
Similar content being viewed by others
References
Brodbelt, J.S.: Shedding light on the frontier of photodissociation. J. Am. Soc. Mass Spectrom. 22, 197–206 (2011)
Kelly, O., Duffy, M.J., King, R.B., Belshaw, L., Williams, I.D., Sa, J., Calvert, C.R., Greenwood, J.B.: Femtosecond lasers for mass spectrometry: proposed application to catalytic hydrogenation of butadiene. Analyst 137, 64–69 (2012)
Peng, J., Puskas, N., Corkum, P.B., Rayner, D.M., Loboda, A.V.: High-pressure gas phase femtosecond laser ionization mass spectrometry. Anal. Chem. 84, 5633–5640 (2012)
Chang, Y.-C., Imasaka, T.: Simple pretreatment procedure combined with gas chromatography/multiphoton ionization/mass spectrometry for the analysis of dioxins in soil samples obtained after the Tohoku earthquake. Anal. Chem. 85, 349–354 (2013)
Watanabe-Ezoe, Y., Li, X., Imasaka, T., Uchimura, T., Imasaka, T.: Gas chromatography/femtosecond multiphoton ionization/time-of-flight mass spectrometry of dioxins. Anal. Chem. 82, 6519–6525 (2010)
Sleno, L., Volmer, D.A.: Ion activation methods for tandem mass spectrometry. J. Mass Spectrom. 39, 1091–1112 (2004)
Kalcic, C.L., Gunaratne, T., Jones, A.D., Dantus, M., Reid, G.E.: Femtosecond laser-induced ionization/ dissociation of protonated peptides. J. Am. Chem. Soc. 131, 940–942 (2009)
Zhu, X., Kalcic, C.L., Winkler, N., Lozovoy, V.V., Dantus, M.: Applications of femtochemistry to proteomic and metabolomic analysis. J. Phys. Chem. A 114, 10380–10387 (2010)
Brixner, T., Gerber, G.: Quantum control of gas-phase and liquid-phase femtochemistry. ChemPhysChem 4, 418–443 (2003)
Lozovoy, V.V., Zhu, X., Gunaratne, T.C., Harris, D.A., Dantus, M.: Control of molecular fragmentation using shaped femtosecond pulses. J. Phys. Chem. A 112, 3789–3812 (2008)
Laarmann, T., Shchatsinin, I., Singh, P., Zhavoronkov, N., Schulz, C.P., Hertel, I.V.: Femtosecond pulse shaping as analytic tool in mass spectrometry of complex polyatomic systems. J. Phys. B At. Mol. Opt. Phys. 41, 074005 (2008)
Zhang, X.S., Schneider, E., Taft, G., Kapteyn, H., Murnane, M., Backus, S.: Multi-microjoule, MHz repetition rate Ti:sapphire ultrafast regenerative amplifier system. Opt. Express 20, 7015–7021 (2012)
Lezius, M., Blanchet, V., Ivanov, M.Y., Stolow, A.: Polyatomic molecules in strong laser fields: nonadiabatic multielectron dynamics. J. Chem. Phys. 117, 1575–1588 (2002)
Markevitch, A.N., Romanov, D.A., Smith, S.M., Schlegel, H.B., Ivanov, M.Y., Levis, R.J.: Sequential nonadiabatic excitation of large molecules and ions driven by strong laser fields. Phys. Rev. A 69, 013401 (2004)
Dundas, D.: Multielectron effects in high harmonic generation in N2 and benzene: simulation using a non-adiabatic quantum molecular dynamics approach for laser-molecule interactions. J. Chem. Phys. 136, 194303 (2012)
Kalcic, C.L., Reid, G.E., Lozovoy, V.V., Dantus, M.: Mechanism elucidation for nonstochastic femtosecond laser-induced ionization/dissociation: from amino acids to peptides. J. Phys. Chem. A 116, 2764–2774 (2012)
Smith, S.A., Kalcic, C.L., Safran, K.A., Stemmer, P.M., Dantus, M., Reid, G.E.: Enhanced characterization of singly protonated phosphopeptide ions by femtosecond laser-induced ionization/dissociation tandem mass spectrometry (fs-LID-MS/MS). J. Am. Soc. Mass Spectrom. 21, 2031–2040 (2010)
Weinkauf, R., Aicher, P., Wesley, G., Grotemeyer, J., Schlag, E.W.: Femtosecond versus nanosecond multiphoton ionization and dissociation of large molecules. J. Phys. Chem. 98, 8381–8391 (1994)
Weinkauf, R., Schanen, P., Yang, D., Soukoura, S., Schlag, E.W.: Elementary processes in peptides: electron mobility and dissociation in peptide cations in the gas phase. J. Phys. Chem. 99, 11255–11265 (1995)
Weinkauf, R., Schanen, P., Metsala, A., Schlag, E.W., Bürgle, M., Kessler, H.: Highly efficient charge transfer in peptide cations in the gas phase: threshold effects and mechanism. J. Phys. Chem. 100, 18567–18585 (1996)
Vorsa, V., Kono, T., Willey, K.F., Winograd, N.: Femtosecond photoionization of ion beam desorbed aliphatic and aromatic amino acids: fragmentation via α-cleavage reactions. J. Phys. Chem. B 103, 7889–7895 (1999)
Cui, W., Hu, Y., Lifshitz, C.: Time resolved photodissociation of small peptide ions. Eur. Phys. J. D 20, 565–571 (2002)
Tembreull, R., Lubman, D.M.: Resonant two-photon ionization of small peptides using pulsed laser desorption in supersonic beam mass spectrometry. Anal. Chem. 59, 1003–1006 (1987)
Lockyer, N., Vickerman, J.C.: Multiphoton ionization mass spectrometry of small biomolecules with nanosecond and femtosecond laser pulses. Int. J. Mass Spectrom. 176, 77–86 (1998)
Lockyer, N., Vickerman, J.C.: Single photon and femtosecond multiphoton ionization of the dipeptide valyl-valine. Int. J. Mass Spectrom. 197, 197–209 (2000)
Willingham, D., Kucher, A., Winograd, N.: Strong-field ionization of sputtered molecules for biomolecular imaging. Chem. Phys. Lett. 468, 264–269 (2009)
Grégoire, G., Dedonder-Lardeux, C., Jouvet, C., Desfrancois, C., Fayeton, J.A.: Ultrafast excited state dynamics in protonated GWG and GYG tripeptides. Phys. Chem. Chem. Phys. 9, 78–82 (2007)
Pérot, M., Lucas, B., Barat, M., Fayeton, J.A., Jouvet, C.: Mechanisms of UV photodissociation of small protonated peptides. J. Phys. Chem. A 114, 3147–3156 (2010)
Kelly, O., Calvert, C.R., Greenwood, J.B., Zettergren, H., Nielsen, S.B., Wyer, J.A.: Effects of charge location on the absorptions and lifetimes of protonated tyrosine peptides in vacuo. J. Phys. Chem. A 116, 1701–1709 (2012)
Posthumus, J.H.: The dynamics of small molecules in intense laser fields. Rep. Prog. Phys. 67, 623–665 (2004)
Calvert, C.R., Bryan, W.A., Newell, W.R., Williams, I.D.: Time-resolved studies of ultrafast wavepacket dynamics in hydrogen molecules. Phys. Rep. 491, 1–28 (2010)
Keldysh, L.V.: Ionization in the field of a strong electromagnetic wave. Sov. Phys. - JETP 20, 1307–1314 (1965)
DeWitt, M.J., Levis, R.J.: Observing the transition from a multiphoton-dominated to a field-mediated ionization process for polyatomic molecules in intense laser fields. Phys. Rev. Lett. 81, 5101–5104 (1998)
DeWitt, M.J., Levis, R.J.: Calculating the Keldysh adiabaticity parameter for atomic, diatomic, and polyatomic molecules. J. Chem. Phys. 108, 7739–7742 (1998)
Hankin, S.M., Villeneuve, D.M., Corkum, P.B., Rayner, D.M.: Nonlinear ionization of organic molecules in high intensity laser fields. Phys. Rev. Lett. 84, 5082–5085 (2000)
Muth-Böhm, J., Becker, A., Faisal, F.H.M.: Suppressed molecular ionization for a class of diatomics in intense femtosecond laser fields. Phys. Rev. Lett. 85, 2280–2283 (2000)
Boguslavskiy, A.E., Mikosch, J., Gijsbertsen, A., Spanner, M., Patchkovskii, S., Gador, N., Vrakking, M.J.J., Stolow, A.: The multielectron ionization dynamics underlying attosecond strong-field spectroscopies. Science 335, 1336–1340 (2012)
Savitski, M.M., Nielsen, M.L., Zubarev, R.A.: Side-chain losses in electron capture dissociation to improve peptide identification. Anal. Chem. 79, 2296–2302 (2007)
van Grondelle, R., Novoderezhkin, V.I.: Quantum effects in photosynthesis. Procedia Chem. 3, 198–210 (2011)
Cordes, M., Giese, B.: Electron transfer in peptides and proteins. Chem. Soc. Rev. 38, 892–901 (2009)
Becker, D., Adhikary, A., Sevilla, M.D.: The Role of Charge and Spin Migration in DNA Radiation Damage. In: Chakraborty, T. (ed.) Charge Migration in DNA, pp. 139–175. New York, Springer (2007)
González-Magana, O., Reitsma, G., Bari, S., Hoekstra, R., Schlatöhlter, T.: Length effects in VUV photofragmentation of protonated peptides. Phys. Chem. Chem. Phys. 14, 4351–4354 (2012)
Lehr, L., Horneff, T., Weinkauf, R., Schlag, E.W.: Femtosecond dynamics after ionization: 2-phenylethyl-N,N-dimethylamine as a model system for non-resonant downhill charge transfer in peptides. J. Phys. Chem. A 109, 8074–8080 (2005)
Belshaw, L., Calegari, F., Duffy, M.J., Trabattoni, A., Poletto, L., Nisoli, M., Greenwood, J.B.: Observation of ultrafast charge migration in an amino acid. J. Phys. Chem. Lett. 3, 3751–3754 (2012)
Cederbaum, L.S., Zobeley, J.: Ultrafast charge migration by electron correlation. Chem. Phys. Lett. 307, 205–210 (1999)
Remacle, F., Levine, R.D.: An electronic time scale in chemistry. Proc. Natl. Acad. Sci. U. S. A. 103, 6793–6798 (2006)
Kuleff, A.I., Lünnemann, S., Cederbaum, L.S.: Electron-correlation-driven charge migration in oligopeptides. Chem. Phys. 414, 100–105 (2013)
Roepstorff, P., Fohlman, J.: Proposal for a common nomenclature for sequence ions in mass spectra of peptides. Biomed. Mass Spectrom. 11, 601 (1984)
Greenwood, J.B., Kelly, O., Calvert, C.R., Duffy, M.J., King, R.B., Belshaw, L., Graham, L., Alexander, J.D., Williams, I.D., Bryan, W.A., Turcu, I.C.E., Cacho, C.M., Springate, E.: A comb-sampling method for enhanced mass analysis in linear electrostatic ion traps. Rev. Sci. Instrum. 82, 043103 (2011)
Calvert, C.R., Belshaw, L., Duffy, M.J., Kelly, O., King, R.B., Smyth, A.G., Kelly, T.J., Costello, J.T., Timson, D.J., Bryan, W.A., Kierspel, T., Rice, P., Turcu, I.C.E., Cacho, C.M., Springate, E., Williams, I.D., Greenwood, J.B.: LIAD-fs Scheme for studies of ultrafast laser interactions with gas phase biomolecules. Phys. Chem. Chem. Phys. 14, 6289–6297 (2012)
Turcu, I.C.E., Springate, E., Froud, C.A., Cacho, C.M., Collier, J.L., Bryan, W.A., Nemeth, G.R.A.J., Marangos, J.P., Tisch, J.W.G., Torres, R., Siegel, T., Brugnera, L., Underwood, J.G., Procino, I., Newell, W.R., Altucci, C., Velotta, R., King, R.B., Alexander, J.D., Calvert, C.R., Kelly, O., Greenwood, J.B., Williams, I.D., Cavalleri, A., Petersen, J.C., Dean, N., Dhesi, S.S., Poletto, L., Villoresi, P., Frassetto, F., Bonora, S., Roper, M.D.: Ultrafast science and development at the Artemis facility. Proc. SPIE Int. Soc. Opt. Eng. 7469, 746902 (2009)
Schlag, E.W., Sheu, S.-Y., Yang, D.-H., Selzle, H.L., Lin, S.H.: Distal charge transport in peptides Angew. Chem. Int. Ed. 46, 3196–3210 (2007)
Stein, S.E.: “Mass Spectra”. In: Linstrom, P.J., Mallard, W.G. (eds.) NIST Chemistry WebBook, NIST Standard Reference Database Number 69. National Institute of Standards and Technology, Gaithersburg MD, 20899. Available at: http://webbook.nist.gov. Accessed: April 15, 2013
Wilson, K.R., Belau, L., Nicolas, C., Jimenez-Cruz, M., Leone, S.R., Ahmed, M.: Direct determination of the ionization energy of histidine with VUV synchrotron radiation. Int. J. Mass Spectrom. 249/250, 155–161 (2006)
Jochims, H.-W., Schwell, M., Chotin, J.-L., Clemino, M., Dulieu, F., Baumgärtel, H., Leach, S.: Photo-ion mass spectrometry of five amino acids in the 6–22 eV photon energy range. Chem. Phys. 298, 279–297 (2004)
Plekan, O., Feyer, V., Richter, R., Coreno, M., Prince, K.C.: Valence photoionization and photofragmentation of aromatic amino acids. Mol. Phys. 106, 1143–1153 (2008)
Peptide Fragmentation Modeller, Biological MS Data and Software Distribution Center, Pacific Northwest National Laboratory
Schlag, E.W., Selzle, H.L., Schanen, P., Weinkauf, R., Levine, R.D.: Dissociation kinetics of peptide ions. J. Phys. Chem. A 110, 8497–8500 (2006)
Horsch, P., Urbasch, G., Weitzel, K.-M.: Analysis of chirality by femtosecond laser ionization mass spectrometry. Chirality 24, 684–690 (2012)
Lux, C., Wollenhaupt, M., Bolze, T., Liang, Q., Köhler, J., Sarpe, C., Baumert, T.: Circular dichroism in the photoelectron angular distributions of camphor and fenchone from multiphoton ionization with femtosecond laser pulses. Angew. Chem. Int. Ed. 51, 5001–5005 (2012)
Acknowledgments
The authors acknowledge support for this work by the Leverhulme Trust, STFC through access to the Artemis Laser Facility, and EPSRC through the STFC Laser Loan Pool. C.R.C. acknowledges support from EPSRC through the Postdoctoral Fellowship Programme (grant number EP/H027319/1). L.B. and M.J.D. acknowledge the support of the Department of Employment and Learning, Northern Ireland. T.J.K. and J.T.C. acknowledge support from Science Foundation Ireland. The authors also acknowledge the technical assistance provided by Phil Rice at the Artemis Laser Facility.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Duffy, M.J., Kelly, O., Calvert, C.R. et al. Fragmentation of Neutral Amino Acids and Small Peptides by Intense, Femtosecond Laser Pulses. J. Am. Soc. Mass Spectrom. 24, 1366–1375 (2013). https://doi.org/10.1007/s13361-013-0653-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13361-013-0653-6