title: Mechanism of nitric oxide induced deamination of cytosine.
abstract: A five-step mechanism is proposed for the NO -induced deamination of cytosine. It has been investigated using DFT calculations, including both explicit water molecules and a bulk solvent model to mimic an aqueous environment. According to this mechanism, cytosine first undergoes tautomerization with the assistance of a water molecule from the bulk. A NO(+) cation produced by the autooxidation of NO is subsequently added to the exocyclic imino group of the cytosine imine tautomer. The resulting adduct is able to undergo a tautomerization step with the participation of a water molecule to produce a cytosine in which a -N(2)OH group is attached to carbon C4. Protonation of the oxygen of the latter gives a water molecule which dissociates instantaneously, leading to a pyrimidinic diazonium cation. This constitutes the rate-determining step of the mechanism with an activation free energy of 92.6 kJ mol(-1). The last step, which is highly exergonic, represents the driving force of the reaction. It is the substitution of the -N(2)(+) terminal group by a water molecule which simultaneously allows the transfer of one of the two hydrogens to the bulk. Thus, the two products of the reaction consist of a nitrogen molecule and the enol tautomer of uracil in equilibrium with the keto form.
authors.affiliation: Laboratoire des Lésions des Acides Nucléiques, INAC/SCIB-UMR-E no. 3 CEA/UJF, CEA Grenoble, F-38054, Grenoble, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Labet
authors.forename: André
authors.initials: A
authors.lastname: Grand
authors.forename: Christophe
authors.initials: C
authors.lastname: Morell
authors.forename: Jean
authors.initials: J
authors.lastname: Cadet
authors.forename: Leif A
authors.initials: LA
authors.lastname: Eriksson