Advertisement

Journal of The American Society for Mass Spectrometry

, Volume 29, Issue 9, pp 1835–1847 | Cite as

Structural Investigation of the Hormone Melatonin and Its Alkali and Alkaline Earth Metal Complexes in the Gas Phase

  • Satrajit Chakrabarty
  • Matthew J. DiTucci
  • Giel Berden
  • Jos Oomens
  • Evan R. Williams
Focus: Application of Photons and Radicals for MS: Research Article

Abstract

Gas phase infrared dissociation spectra of the radical cation, deprotonated and protonated forms of the hormone melatonin, and its complexes with alkali (Li+, Na+, and K+) and alkaline earth metal ions (Mg2+, Ca2+, and Sr2+) are measured in the spectral range 800–1800 cm−1. Minimum energy geometries calculated at the B3LYP/LACVP++** level are used to assign structural motifs to absorption bands in the experimental spectra. The melatonin anion is deprotonated at the indole-N. The indole-C linking the amide chain is the most favored protonation site. Comparisons between the experimental and calculated spectra for alkali and alkaline earth metal ion complexes reveal that the metal ions interact similarly with the amide and methoxy oxygen atoms. The amide I band undergoes a red shift with increasing charge density of the metal ion and the amide II band shows a concomitant blue shift. Another binding motif in which the metal ions interact with the amide-O and the π-electron cloud of the aromatic group is identified but is higher in energy by at least 18 kJ/mol. Melatonin is deprotonated at the amide-N with Mg2+ and the metal ion coordinates to the amide-N and an indole-C or the methoxy-O. These results provide information about the intrinsic binding of metal ions to melatonin and combined with future studies on solvated melatonin-metal ion complexes may help elucidate the solvent effects on metal ion binding in solution and the biochemistry of melatonin. These results also serve as benchmarks for future theoretical studies on melatonin-metal ion interactions.

Graphical Abstract

Keywords

Melatonin-metal ion interaction Ion spectroscopy Free electron laser Infrared spectroscopy Infrared multiphoton dissociation 

Notes

Acknowledgements

This material is based upon work supported by the National Science Foundation Division of Chemistry under grant number CHE-1609866 and the Swiss National Science Foundation under grant number P2BSP2_148624. We gratefully acknowledge the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) for the support of the FELIX Laboratory. We thank Prof. Ryan R. Julian for useful discussions and his innovative contributions to studies of ion-photon interactions.

Supplementary material

13361_2018_2020_MOESM1_ESM.docx (24 kb)
ESM 1 (DOCX 24 kb)

References

  1. 1.
    Sugden, D.: Melatonin biosynthesis in the mammalian pineal-gland. Experientia. 45, 922–932 (1989)CrossRefGoogle Scholar
  2. 2.
    Hardeland, R., Pandi-Perumal, S.R., Cardinali, D.P.: Melatonin. Int. J. Biochem. Cell Biol. 38, 313–316 (2006)CrossRefGoogle Scholar
  3. 3.
    Cassone, V.M.: Melatonin's role in vertebrate circadian rhythms. Chronobiol. Int. 15, 457–473 (1998)CrossRefGoogle Scholar
  4. 4.
    Simko, F., Paulis, L.: Melatonin as a potential antihypertensive treatment. J. Pineal Res. 42, 319–322 (2007)CrossRefGoogle Scholar
  5. 5.
    Cardinali, D.P., Srinivasan, V., Brzezinski, A., Brown, G.M.: Melatonin and its analogs in insomnia and depression. J. Pineal Res. 52, 365–375 (2012)CrossRefGoogle Scholar
  6. 6.
    Zang, L.Y., Cosma, G., Gardner, H., Vallyathan, V.: Scavenging of reactive oxygen species by melatonin. Biochim. Biophys. Acta. 1425, 469–477 (1998)CrossRefGoogle Scholar
  7. 7.
    Reiter, R.J., Robinson, J.: Melatonin: Your Body’s Natural Wonder Drug. Bantam Books, New York (1995)Google Scholar
  8. 8.
    Romero, A., Ramos, E., de Los Rios, C., Egea, J., del Pino, J., Reiter, R.J.: A review of metal-catalyzed molecular damage: protection by melatonin. J. Pineal Res. 56, 343–370 (2014)CrossRefGoogle Scholar
  9. 9.
    Lahiri, D.K., Chen, D., Lahiri, P., Rogers, J.T., Greig, N.H., Bondy, S.: Melatonin, metals, and gene expression: implications in aging and neurodegenerative disorders. Ann. N. Y. Acad. Sci. 1035, 216–230 (2004)CrossRefGoogle Scholar
  10. 10.
    Kabuto, H., Yokoi, I., Ogawa, N.: Melatonin inhibits iron-induced epileptic discharges in rats by suppressing peroxidation. Epilepsia. 39, 237–243 (1998)CrossRefGoogle Scholar
  11. 11.
    Lin, A.M., Ho, L.T.: Melatonin suppresses iron-induced neurodegeneration in rat brain. Free Radic. Biol. Med. 28, 904–911 (2000)CrossRefGoogle Scholar
  12. 12.
    Limson, J., Nyokong, T., Daya, S.: The interaction of melatonin and its precursors with aluminium, cadmium, copper, iron, lead, and zinc: an adsorptive voltammetric study. J. Pineal Res. 24, 15–21 (1998)CrossRefGoogle Scholar
  13. 13.
    Lack, B., Daya, S., Nyokong, T.: Interaction of serotonin and melatonin with sodium, potassium, calcium, lithium and aluminium. J. Pineal Res. 31, 102–108 (2001)CrossRefGoogle Scholar
  14. 14.
    Mocchegiani, E., Santarelli, L., Tibaldi, A., Muzzioli, M., Bulian, D., Cipriano, K., Olivieri, F., Fabris, N.: Presence of links between zinc and melatonin during the circadian cycle in old mice: effects on thymic endocrine activity and on the survival. J. Neuroimmunol. 86, 111–122 (1998)CrossRefGoogle Scholar
  15. 15.
    Prell, J.S., Demireva, M., Oomens, J., 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)CrossRefGoogle Scholar
  16. 16.
    Dunbar, R.C., Oomens, J., Berden, G., Lau, J.K., Verkerk, U.H., Hopkinson, A.C., Siu, K.W.: Metal ion complexes with HisGly: comparison with PhePhe and PheGly. J. Phys. Chem. A. 117, 5335–5343 (2013)CrossRefGoogle Scholar
  17. 17.
    Dunbar, R.C., Berden, G., Martens, J.K., Oomens, J.: Divalent metal-ion complexes with dipeptide ligands having Phe and His side-chain anchors: effects of sequence, metal ion, and anchor. J. Phys. Chem. A. 119, 9901–9909 (2015)CrossRefGoogle Scholar
  18. 18.
    Bush, M.F., Oomens, J., Saykally, R.J., Williams, E.R.: Alkali metal ion binding to glutamine and glutamine derivatives investigated by infrared action spectroscopy and theory. J. Phys. Chem. A. 112, 8578–8584 (2008)CrossRefGoogle Scholar
  19. 19.
    Dunbar, R.C., Berden, G., Oomens, J.: How does a small peptide choose how to bind a metal ion? IRMPD and computational survey of CS versus Iminol binding preferences. Int. J. Mass Spectrom. 354, 356–364 (2013)CrossRefGoogle Scholar
  20. 20.
    Ruan, C.H., Yang, Z.B., Hallowita, N., Rodgers, M.T.: Cation-pi interactions with a model for the side chain of tryptophan: structures and absolute binding energies of alkali metal cation-indole complexes. J. Phys. Chem. A. 109, 11539–11550 (2005)CrossRefGoogle Scholar
  21. 21.
    Florio, G.M., Christie, R.A., Jordan, K.D., Zwier, T.S.: Conformational preferences of jet-cooled melatonin: probing trans- and cis-amide regions of the potential energy surface. J. Am. Chem. Soc. 124, 10236–10247 (2002)CrossRefGoogle Scholar
  22. 22.
    Yi, J.T., Brand, C., Wollenhaupt, M., Pratt, D.W., Leo Meerts, W., Schmitt, M.: Rotationally resolved electronic spectroscopy of biomolecules in the gas phase. Melatonin. J. Mol. Spectrosc. 268, 115–122 (2011)CrossRefGoogle Scholar
  23. 23.
    Bayari, S., Ide, S.: Fourier transform infrared spectra and molecular structure of 5-methoxytryptamine, N-acetyl-5-methoxytryptamine and N-phenylsulfonamide-5-methoxytryptamine. Spectrochim. Acta A Mol. Biomol. Spectrosc. 59, 1255–1263 (2003)CrossRefGoogle Scholar
  24. 24.
    Singh, G., Abbas, J.M., Dogra, S.D., Sachdeva, R., Rai, B., Tripathi, S.K., Prakash, S., Sathe, V., Saini, G.S.: Vibrational and electronic spectroscopic studies of melatonin. Spectrochim. Acta A Mol. Biomol. Spectrosc. 118, 73–81 (2014)CrossRefGoogle Scholar
  25. 25.
    Stein, S.E.: Infrared Spectra in NIST Chemistry WebBook. In: Mallard, W.G., Linstrom, P.J. (eds.) NIST Standard Reference Database Number 69. National Institute of Standards and Technology, Gaithersburg, 20899.  https://doi.org/10.18434/T4D303, (retrieved March 18, 2018)
  26. 26.
    Dunbar, R.C., Steill, J.D., Oomens, J.: Conformations and vibrational spectroscopy of metal-ion/polylalanine complexes. Int. J. Mass Spectrom. 297, 107–115 (2010)CrossRefGoogle Scholar
  27. 27.
    Bongiorno, D., Ceraulo, L., Camarda, L., Ciofalo, M., Ferrugia, M., Indelicato, S., Mele, A., Liveri, V.T.: Gas-phase ion chemistry of protonated melatonin. Eur J Mass Spectrom (Chichester, Eng). 15, 199–208 (2009)CrossRefGoogle Scholar
  28. 28.
    Valle, J.J., Eyler, J.R., Oomens, J., Moore, D.T., van der Meer, A.F.G., von Helden, G., Meijer, G., Hendrickson, C.L., Marshall, A.G., Blakney, G.T.: Free electron laser-Fourier transform ion cyclotron resonance mass spectrometry facility for obtaining infrared multiphoton dissociation spectra of gaseous ions. Rev. Sci. Instrum. 76, 023103-1–023103-7 (2005)Google Scholar
  29. 29.
    Shao, Y.H., Gan, Z.T., Epifanovsky, E., Gilbert, A.T.B., Wormit, M., Kussmann, J., Lange, A.W., Behn, A., Deng, J., Feng, X.T., Ghosh, D., Goldey, M., Horn, P.R., Jacobson, L.D., Kaliman, I., Khaliullin, R.Z., Kus, T., Landau, A., Liu, J., Proynov, E.I., Rhee, Y.M., Richard, R.M., Rohrdanz, M.A., Steele, R.P., Sundstrom, E.J., Woodcock, H.L., Zimmerman, P.M., Zuev, D., Albrecht, B., Alguire, E., Austin, B., Beran, G. J.O., Bernard, Y.A., Berquist, E., Brandhorst, K., Bravaya, K.B., Brown, S.T., Casanova, D., Chang, C.M., Chen, Y.Q., Chien, S.H., Closser, K.D., Crittenden, D.L., Diedenhofen, M., DiStasio, R.A., Do, H., Dutoi, A.D., Edgar, R.G., Fatehi, S., Fusti-Molnar, L., Ghysels, A., Golubeva-Zadorozhnaya, A., Gomes, J., Hanson-Heine, M.W.D., Harbach, P.H.P., Hauser, A.W., Hohenstein, E.G., Holden, Z.C., Jagau, T.C., Ji, H.J., Kaduk, B., Khistyaev, K., Kim, J., Kim, J., King, R.A., Klunzinger, P., Kosenkov, D., Kowalczyk, T., Krauter, C.M., Lao, K.U., Laurent, A.D., Lawler, K.V., Levchenko, S.V., Lin, C.Y., Liu, F., Livshits, E., Lochan, R.C., Luenser, A., Manohar, P., Manzer, S.F., Mao, S.P., Mardirossian, N., Marenich, A.V., Maurer, S.A., Mayhall, N.J., Neuscamman, E., Oana, C.M., Olivares-Amaya, R., O’Neill, D.P., Parkhill, J.A., Perrine, T.M., Peverati, R., Prociuk, A., Rehn, D.R., Rosta, E., Russ, N.J., Sharada, S.M., Sharma, S., Small, D.W., Sodt, A., Stein, T., Stuck, D., Su, Y.C., Thom, A.J.W., Tsuchimochi, T., Vanovschi, V., Vogt, L., Vydrov, O., Wang, T., Watson, M. A., Wenzel, J., White, A., Williams, C.F., Yang, J., Yeganeh, S., Yost, S.R., You, Z.Q., Zhang, I.Y., Zhang, X., Zhao, Y., Brooks, B.R., Chan, G.K.L., Chipman, D.M., Cramer, C.J., Goddard, W.A., Gordon, M.S., Hehre, W.J., Klamt, A., Schaefer, H.F., Schmidt, M.W., Sherrill, C.D., Truhlar, D.G., Warshel, A., Xu, X., Aspuru-Guzik, A., Baer, R., Bell, A.T., Besley, N.A., Chai, J.D., Dreuw, A., Dunietz, B.D., Furlani, T.R., Gwaltney, S.R., Hsu, C.P., Jung, Y.S., Kong, J., Lambrecht, D.S., Liang, W.Z., Ochsenfeld, C., Rassolov, V.A., Slipchenko, L.V., Subotnik, J.E., Van Voorhis, T., Herbert, J.M., Krylov, A.I., Gill, P.M.W., Head-Gordon, M: Advances in molecular quantum chemistry contained in the Q-Chem 4 program package. Mol. Phys. 113, 184–215 (2015)Google Scholar
  30. 30.
    Polfer, N.C., Oomens, J.: Vibrational spectroscopy of bare and solvated ionic complexes of biological relevance. Mass Spectrom. Rev. 28, 468–494 (2009)CrossRefGoogle Scholar
  31. 31.
    Mostad, A., Romming, C.: The crystal and molecular structure of N-acetyl-5-methoxy-tryptamine (melatonin). Acta Chem. Scand. B. 28, 564–572 (1974)CrossRefGoogle Scholar
  32. 32.
    Wakahara, A., Fujiwara, T., Tomita, K.: The crystal and molecular structure of melatonin, N-acetyl-5-methoxytryptamine. Chem. Lett. 1, 1139–1142 (1972)CrossRefGoogle Scholar
  33. 33.
    Mayne, L.C., Hudson, B.: Resonance Raman-spectroscopy of N-methylacetamide—overtones and combinations of the C-N stretch (amide-Ii') and effect of solvation on the C=O stretch (amide-I) intensity. J. Phys. Chem. 95, 2962–2967 (1991)CrossRefGoogle Scholar
  34. 34.
    Carr, J.K., Zabuga, A.V., Roy, S., Rizzo, T.R., Skinner, J.L.: Assessment of amide I spectroscopic maps for a gas-phase peptide using IR-UV double-resonance spectroscopy and density functional theory calculations. J. Chem. Phys. 140, 224111-1–224111-9 (2014)Google Scholar
  35. 35.
    Dunbar, R.C., Steill, J.D., Polfer, N.C., Berden, G., Oomens, J.: Peptide bond tautomerization induced by divalent metal ions: characterization of the iminol configuration. Angew. Chem. 51, 4591–4593 (2012)CrossRefGoogle Scholar
  36. 36.
    Dunbar, R.C., Polfer, N.C., Berden, G., Oomens, J.: Metal ion binding to peptides: oxygen or nitrogen sites? Int. J. Mass Spectrom. 330, 71–77 (2012)CrossRefGoogle Scholar
  37. 37.
    Voronina, L., Rizzo, T.R.: Spectroscopic studies of kinetically trapped conformations in the gas phase: the case of triply protonated bradykinin. Phys. Chem. Chem. Phys. 17, 25828–25836 (2015)CrossRefGoogle Scholar
  38. 38.
    Bush, M.F., O'Brien, J.T., Prell, J.S., Saykally, R.J., Williams, E.R.: Infrared spectroscopy of cationized arginine in the gas phase: direct evidence for the transition from nonzwitterionic to zwitterionic structure. J. Am. Chem. Soc. 129, 1612–1622 (2007)CrossRefGoogle Scholar
  39. 39.
    Bush, M.F., Prell, J.S., Saykally, R.J., Williams, E.R.: One water molecule stabilizes the cationized arginine zwitterion. J. Am. Chem. Soc. 129, 13544–13553 (2007)CrossRefGoogle Scholar
  40. 40.
    Kamariotis, A., Boyarkin, O.V., Mercier, S.R., Beck, R.D., Bush, M.F., Williams, E.R., Rizzo, T.R.: Infrared spectroscopy of hydrated amino acids in the gas phase: protonated and lithiated valine. J. Am. Chem. Soc. 128, 905–916 (2006)CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2018

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of CaliforniaBerkeleyUSA
  2. 2.Laboratory of Physical ChemistryZurichSwitzerland
  3. 3.Institute for Molecules and Materials, FELIX LaboratoryRadboud University NijmegenNijmegenThe Netherlands
  4. 4.Van’t Hoff Institute for Molecular SciencesUniversity of AmsterdamAmsterdamThe Netherlands

Personalised recommendations