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Density Functional Theory Study of Hypoxanthine Tautomerism in Both the Isolated State and a Modeled-Ideal Aqueous Solution at Several Heterocyclic Protonation Levels

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Abstract

In order to advance the knowledge of prototropic tautomerism from the physicochemical point of view, the purine derivative hypoxanthine has been selected and studied. The overall purpose has been to explore thermodynamic aspects of the heterocycle tautomerism under the influence of both its protonation level and the surrounding dielectric constant. A Density Functional Theory study (at the B3LYP/6-31++G** level) was performed, in which the energetic and thermodynamic stabilities, the electric dipole moment values, the tautomeric equilibrium constants and the tautomeric populations were obtained for several hypoxanthine tautomers under systematically modified heterocyclic protonation levels, considering both isolated and ideal aqueous solution states. Among the interesting results obtained are changes in the tautomeric populations for several heterocyclic protonation states and with the increase of the dielectric constant. Several of the predictions made for an aqueous solution show good agreement with recently reported experimental conclusions. Also, the ionizable groups that contribute to the different hypoxanthine ionization steps in the main tautomers have been established. These and other related results are presented and discussed. Finally, the confidence developed in the predicted tautomeric populations in a modeled-ideal aqueous solution allows us to propose that the methodology applied here can be used for the study of prototropic tautomerism in heterocycles belonging to this class, particularly when the experimental work is challenging in both performance and physicochemical data analysis.

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References

  1. Costas, M.E., Acevedo-Chávez, R.: Density functional study of neutral hypoxanthine tautomeric forms. J. Phys. Chem. A 101, 8309–8318 (1997)

    Article  CAS  Google Scholar 

  2. Lin, J., Yu, C., Peng, S., Akiyama, I., Li, K., Lee, L.K., LeBreton, P.R.: Ultraviolet photoelectron studies of the ground-state electronic structure and gas-phase tautomerism of hypoxanthine and guanine. J. Phys. Chem. 84, 1006–1012 (1980)

    Article  CAS  Google Scholar 

  3. Sheina, G.G., Stepanian, S.G., Rádchenko, E.D., Blagoi, Yu.P.: IR-Spectra of guanine and hypoxanthine isolated molecules. J. Mol. Struct., Theochem 158, 275–292 (1987)

    CAS  Google Scholar 

  4. Shukla, M.K., Leszczynski, J.: Theoretical study of proton transfer in hypoxanthine tautomers: Effects of hydration. J. Phys. Chem. A 104, 3021–3027 (2000)

    Article  CAS  Google Scholar 

  5. Ramaekers, R., Maes, G., Adamowicz, L., Dkhissi, A.: Matrix-isolation FT-IR study and theoretical calculations of the vibrational, tautomeric and H-bonding properties of hypoxanthine. J. Mol. Struct., Theochem 560, 205–221 (2001)

    CAS  Google Scholar 

  6. Ramaekers, R., Dkhissi, A., Adamowicz, L., Maes, G.: Matrix-isolation FT-IR study and theoretical calculations of the hydrogen-bond interaction of hypoxanthine with H2O. J. Phys. Chem. A 106, 4502–4512 (2002)

    Article  CAS  Google Scholar 

  7. Gerega, A., Lapinski, L., Nowak, M.J., Rostkowska, H.: UV-induced oxo → hydroxy unimolecular proton-transfer reactions in hypoxanthine. J. Phys. Chem. A 110, 10236–10244 (2006)

    Article  CAS  Google Scholar 

  8. Lichtenberg, D., Bergmann, F., Neiman, Z.: New observations on tautomerism and ionization processes in hypoxanthines and 6-thiopurines. Isr. J. Chem. 10, 805–817 (1972)

    CAS  Google Scholar 

  9. Twanmoh, L.M., Wood, H.B. Jr., Driscoll, J.S.: NMR spectral characteristics of N–H protons in purine derivatives. J. Heterocycl. Chem. 10, 187–190 (1973)

    Article  CAS  Google Scholar 

  10. Chenon, M.T., Pugmire, R.J., Grant, D.M., Panzica, R.P., Townsend, L.B.: C-13 magnetic-resonance. 26. Quantitative-determination of tautomeric populations of certain purines. J. Am. Chem. Soc. 97, 4636–4642 (1975)

    Article  CAS  Google Scholar 

  11. Ulichy, J., Ghomi, M., Tomkova, A., Miskovsky, P., Turpin, P.Y., Chinsky, L.: Vibrational analysis and molecular-force field of hypoxanthine as determined from ultraviolet resonance Raman-spectra of native and deuterated species. Eur. Biophys. J. 23, 115–123 (1994)

    Google Scholar 

  12. Chowdhury, J., Mukherjee, K.M., Misra, T.N.: A pH dependent surface-enhanced Raman scattering study of hypoxanthine. J. Raman Spectrosc. 31, 427–431 (2000)

    Article  CAS  Google Scholar 

  13. Lusty, J.R. (ed.): CRC Handbook of Nucleobase Complexes, vol. I. CRC Press, Boca Raton (1990)

    Google Scholar 

  14. Tauler, R., Cid, J.F., Casassas, E.: Potentiometric and H-1-NMR study of the interaction of hypoxanthine and inosine with H+, Cu(II), and Zn(II). J. Inorg. Biochem. 39, 277–285 (1990)

    Article  CAS  Google Scholar 

  15. San Román-Zimbrón, M.L., Costas, M.E., Acevedo-Chávez, R.: Neutral hypoxanthine in aqueous solution: quantum chemical and Monte Carlo studies. J. Mol. Struct., Theochem 711, 83–94 (2004), and references therein

    Article  Google Scholar 

  16. Hernández, B., Luque, F.J., Orozco, M.: Tautomerism of xanthine oxidase substrates hypoxanthine and allopurinol. J. Org. Chem. 61, 5964–5971 (1996)

    Article  Google Scholar 

  17. Civcir, P.: AM1 and PM3 study of tautomerism of hypoxanthine in the gas and aqueous phases. Struct. Chem. 12, 15–21 (2001)

    Article  CAS  Google Scholar 

  18. Costas, M.E., Acevedo-Chávez, R.: Density functional study of the monocationic hypoxanthine tautomeric forms. J. Mol. Struct., Theochem 489, 73–85 (1999)

    Article  CAS  Google Scholar 

  19. Costas, M.E., Acevedo-Chávez, R.: Density functional study of the dicationic hypoxanthine tautomeric forms. J. Mol. Struct., Theochem 468, 39–50 (1999)

    Article  CAS  Google Scholar 

  20. Acevedo-Chávez, R., Costas, M.E.: Purine derivative hypoxanthine physicochemical and chemical behavior. The density functional point of view. Recent Res. Devel. Phys. Chem. 3, 23–52 (1999)

    Google Scholar 

  21. Costas, M.E., Acevedo-Chávez, R.: Density functional study of the three-protonated hypoxanthine3+ isomeric forms. J. Mol. Struct., Theochem 532, 143–156 (2000)

    Article  CAS  Google Scholar 

  22. Costas, M.E., Acevedo-Chávez, R.: Density functional study of the anionic hypoxanthine tautomeric forms. J. Mol. Struct., Theochem 499, 71–84 (2000)

    Article  CAS  Google Scholar 

  23. Woolley, E.M., Wilton, R.W., Hepler, L.G.: Thermodynamics of proton dissociations from imidazolium ion, 6-uracilcarboxylic acid, and protonated hypoxanthine in aqueous solution. Can. J. Chem. 48, 3249–3252 (1970)

    Article  CAS  Google Scholar 

  24. Benoit, R.L., Fréchette, M.: Protonation of hypoxanthine, guanine, xanthine, and caffeine. Can. J. Chem. 63, 3053–3056 (1985)

    Article  CAS  Google Scholar 

  25. Fernández-Quejo, M., de la Fuente, M., Navarro, R.: Theoretical calculations and vibrational study of hypoxanthine in aqueous solution. J. Mol. Struct. 744–747, 749–757 (2005)

    Article  Google Scholar 

  26. Gogia, S., Jain, A., Puranik, M.: Structures, ionization equilibria, and tautomerism of 6-oxopurines in solution. J. Phys. Chem. B 113, 15101–15118 (2009)

    Article  CAS  Google Scholar 

  27. Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Zakrzewski, V.G., Montgomery, J.A. Jr., Stratmann, R.E., Burant, J.C., Dapprich, S., Millam, J.M., Daniels, A.D., Kudin, K.N., Strain, M.C., Farkas, O., Tomasi, J., Barone, V., Cossi, M., Cammi, R., Mennucci, B., Pomelli, C., Adamo, C., Clifford, S., Ochterski, J., Petersson, G.A., Ayala, P.Y., Cui, Q., Morokuma, K., Malick, D.K., Rabuck, A.D., Raghavachari, K., Foresman, J.B., Cioslowski, J., Ortiz, J.V., Baboul, A.G., Stefanov, B.B., Liu, G., Liashenko, A., Piskorz, P., Komaromi, I., Gomperts, R., 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., Andres, J.L., Gonzalez, C., Head-Gordon Replogle, E.S., Pople, J.A.: Gaussian98, Revisión A.7. Gaussian, Inc., Pittsburgh, PA (1998)

  28. Martínez-Ríos, F.: Molecular simulation of neutral hypoxanthine in aqueous solution with a polarizable model. M.Sc. thesis, Facultad de Química, Universidad Nacional Autónoma de México, México (2011)

  29. Martell, A.E., Motekaitis, R.J.: Determination and Use of Stability Constants, 2nd edn. Wiley-VCH, New York (1992)

    Google Scholar 

  30. Jang, Y.H., Goddard, W.A. III, Noyes, K.T., Sowers, L.C., Hwang, S., Chung, D.S.: pKa values of guanine in water: Density functional theory calculations combined with Poisson–Boltzmann continuum-solvation model. J. Phys. Chem. B 107, 344–357 (2003)

    Article  CAS  Google Scholar 

  31. Shugar, D., Psoda, A.: Biophysics of nucleic acids. In: Saenger, W. (ed.): Landholt–Bornstein New Series VII/Id, pp. 308–348. Springer, Berlin (1990)

    Google Scholar 

  32. Hanus, M., Ryjáček, F., Kabeláč, M., Kubař, T., Bogdan, T.V., Trygubenko, S.A., Hobza, P.: Correlated ab initio study of nucleic acid bases and their tautomers in the gas phase, in a microhydrated environment and in aqueous solution. Guanine: surprising stabilization of rare tautomers in aqueous solution. J. Am. Chem. Soc. 125, 7678–7688 (2003)

    Article  CAS  Google Scholar 

  33. Shukla, M.K., Mishra, S.K., Kumar, A., Mishra, P.C.: An ab initio study of excited states of guanine in the gas phase and aqueous media: Electronic transitions and mechanism of spectral oscillations. J. Comput. Chem. 21, 826–846 (2000)

    Article  CAS  Google Scholar 

  34. Kushwaha, P.S., Kumar, A., Mishra, P.C.: Electronic transitions of guanine tautomers, their stacked dimers, trimers and sodium complexes. Spectrochim. Acta, Part A, Mol. Biomol. Spectrosc. 60, 719–728 (2004)

    Article  CAS  Google Scholar 

  35. Pugmire, R.J., Grant, D.M.: C-13 magnetic resonance. 19. Benzimidazole, purine, and their anionic and cationic species. J. Am. Chem. Soc. 93, 1880–1887 (1971)

    Article  Google Scholar 

  36. Schumacher, M., Günther, H.: C-13, H-1 Spin spin coupling. 9. Purine. J. Am. Chem. Soc. 104, 4167–4173 (1982)

    Article  CAS  Google Scholar 

  37. Gonnella, N.C., Roberts, J.D.: Studies of the tautomerism of purine and the protonation of purine and its 7-methyl and 9-methyl derivatives by N-15 nuclear magnetic-resonance spectroscopy. J. Am. Chem. Soc. 104, 3162–3164 (1982)

    Article  CAS  Google Scholar 

  38. Gonnella, N.C., Nakanishi, H., Holtwick, J.B., Horowitz, D.S., Kanamori, K., Leonard, N.J., Roberts, J.D.: Studies of tautomers and protonation of adenine and its derivatives by N-15 nuclear magnetic-resonance spectroscopy. J. Am. Chem. Soc. 105, 2050–2055 (1983)

    Article  CAS  Google Scholar 

  39. Laxer, A., Major, D.T., Gottlieb, H.E., Fischer, B.: (N-15(5))-labeled adenine derivatives: Synthesis and studies of tautomerism by N-15 NMR spectroscopy and theoretical calculations. J. Org. Chem. 66, 5463–5481 (2001), and references therein

    Article  CAS  Google Scholar 

  40. Hanus, M., Kabeláč, M., Rejnek, J., Ryjáček, F., Hobza, P.: Correlated ab initio study of nucleic acid bases and their tautomers in the gas phase, in a microhydrated environment, and in aqueous solution. Part 3. Adenine. J. Phys. Chem. B 108, 2087–2097 (2004)

    Article  CAS  Google Scholar 

  41. Dybiec, K., Molchanov, S., Gryff-Keller, A.: Structure of neutral molecules and monoanions of selected oxopurines in aqueous solutions as studied by NMR spectroscopy and theoretical calculations. J. Phys. Chem. A 115, 2057–2064 (2011)

    Article  CAS  Google Scholar 

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Acknowledgements

The authors are indebted to the Dirección General de Asuntos del Personal Académico-Universidad Nacional Autónoma de México (IN101208) for financial support.

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  1. Departamento de Fisicoquímica, Facultad de Química, Universidad Nacional Autónoma de México, Cd. Universitaria, C.P. 04510, Mexico D.F., Mexico

    María Eugenia Costas & Rodolfo Acevedo-Chávez

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  1. María Eugenia Costas
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  2. Rodolfo Acevedo-Chávez
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Correspondence to María Eugenia Costas.

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Costas, M.E., Acevedo-Chávez, R. Density Functional Theory Study of Hypoxanthine Tautomerism in Both the Isolated State and a Modeled-Ideal Aqueous Solution at Several Heterocyclic Protonation Levels. J Solution Chem 41, 864–878 (2012). https://doi.org/10.1007/s10953-012-9834-3

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