Mechanism of nitric oxide induced deamination of cytosine

作者：Labet Vanessa; Grand Andre; Morell Christophe; Cadet Jean; Eriksson Leif A^*

来源：Physical Chemistry Chemical Physics, 2009, 11(14): 2379-2386.

DOI：10.1039/b818669c

A five-step mechanism is proposed for the NO(center dot)-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(center dot) 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.

• 出版日期2009
• 单位中国地震局