N.R. Jena - Mechanisms of Formation of 8-Oxoguanine Due To Reactions of One and Two OH• Radicals and the H2O2 Molecule with Guanine: A Quantum Computational Study

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      Publication Details (including relevant citation   information):

      J. Phys. Chem. B, 2005, 109, 14205.

      Abstract:

      Mechanisms of formation of the mutagenic product 8-oxoguanine   (8OG) due to reactions of guanine with two separate   OH radicals and with H2O2 were   investigated at the B3LYP/6-31G**, B3LYP/6-311++G**, and   B3LYP/AUG-cc-pVDZ levels of theory. Single point energy   calculations were carried out with the MP2/AUG-cc-pVDZ method   employing the optimized geometries at the B3LYP/AUG-cc-pVDZ   level. Solvent effect was treated using the PCM and IEF-PCM   models. Reactions of two separate OH radicals and   H2O2 with the C2 position of   5-methylimidazole (5MI) were investigated taking 5MI as a model   to study reactions at the C8 position of guanine. The addition   reaction of an OH radical at the C8 position of   guanine is found to be nearly barrierless while the corresponding   adduct is quite stable. The reaction of a second OH  radical at the C8 position of guanine leading to the formation of   8OG complexed with a water molecule can take place according to   two different mechanisms, involving two steps each. According to   one mechanism, at the first step, 8-hydroxyguanine (8OHG)   complexed with a water molecule is formed ,while at the second   step, 8OHG is tautomerized to 8OG. In the other mechanism, at the   first step, an intermediate complexed (IC) with a water molecule   is formed, the five-membered ring of which is open, while at the   second step, the five-membered ring is closed and a hydrogen   bonded complex of 8OG with a water molecule is formed. The   reaction of H2O2 with guanine leading to   the formation of 8OG complexed with a water molecule can also   take place in accordance with two different mechanisms having two   steps each. At the first step of one mechanism,   H2O2 is dissociated into two OH  groups that react with guanine to form the same IC as that formed   in the reaction with two separate OH radicals, and   the subsequent step of this mechanism is also the same as that of   the reaction of guanine with two separate OH  radicals. At the first step of the other mechanism of the   reaction of guanine with H2O2, the latter   molecule is dissociated into a hydrogen atom and an   OOH group which become bonded to the N7 and C8 atoms   of guanine, respectively. At the second step of this mechanism,   the OOH group is dissociated into an oxygen atom and   an OH group, the former becomes bonded to the C8 atom   of guanine while the latter abstracts the H8 atom bonded to C8,   thus producing 8OG complexed with a water molecule. Solvent   effects of the aqueous medium on certain reaction barriers and   released energies are appreciable. 5MI works as a satisfactory   model for a qualitative study of the reactions of two separate   OH radicals or H2O2 occurring   at the C8 position of guanine.

      Address (URL): http://pubs.acs.org/doi/abs/10.1021/jp050646j