Proton catalyzed hydrolytic deamination of cytosine: a computational study
Résumé
Two pathways involving proton catalyzed hydr-olytic 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 G = =140 kJ/mol. The current mechanism provides a lower barrier to deamina-tion 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). Keywords Cytosine · Hydrolytic deamination · B3LYP · Mutation · DNA Dedicated to Professor Nino Russo on the occasion of his 60th birthday. Electronic supplementary material The online version of this article (