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Proton catalyzed hydrolytic deamination of cytosine: a computational study

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Abstract

Two pathways involving proton catalyzed hydrolytic deamination of cytosine (to uracil) are investigated at the PCM-corrected B3LYP/6-311G(d,p) level of theory, in the presence of an additional catalyzing water molecule. It is concluded that the pathway involving initial protonation at nitrogen in position 3 of the ring, followed by water addition at C4 and proton transfer to the amino group, is a likely route to hydrolytic deamination. The rate determining step is the addition of water to the cytosine, with a calculated free energy barrier in aqueous solution of ΔG ≠=140 kJ/mol. The current mechanism provides a lower barrier to deamination than previous work based on OH − catalyzed reactions, and lies closer to the experimental barrier derived from rate constants (E a = 117  ±  4 kJ/mol).

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Authors and Affiliations

  1. Laboratoire “Lésions des Acides Nucléiques”, DRFMC/SCIB, UMR-E 3 (CEA/UJF), CEA-Grenoble, 17 avenue des Martyrs, 38054, Grenoble Cedex 9, France

    V. Labet, A. Grand, C. Morell & J. Cadet

  2. Department of Natural Sciences and Örebro Life Science Center, Örebro University, 701 82, Örebro, Sweden

    L. A. Eriksson

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  1. V. Labet
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  2. A. Grand
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  3. C. Morell
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  4. J. Cadet
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  5. L. A. Eriksson
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Correspondence to L. A. Eriksson.

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Dedicated to Professor Nino Russo on the occasion of his 60th birthday.

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Labet, V., Grand, A., Morell, C. et al. Proton catalyzed hydrolytic deamination of cytosine: a computational study. Theor Chem Account 120, 429–435 (2008). https://doi.org/10.1007/s00214-008-0418-7

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  • DOI: https://doi.org/10.1007/s00214-008-0418-7

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