Catalytic involvement of CO2 in the mutagenesis caused by reactions of ONOO(-) with guanine

The catalytic role of CO2 in reactions of ONOO- with guanine, leading to the formation of the mutagenic species 8-oxoguanine (8-oxoG) and 8-nitroguanine anion (8-nitroG-), was investigated by considering the reactions of nitrosoperoxycarbonate anion (ONOOCO2-), an adduct of ONOO- and CO2, with guanine at the B3LYP/6-31G** and B3LYP/AUG-cc-pVDZ levels of density functional theory in gas phase. In order to study bulk solvent effect, single-point energy calculations in aqueous media were carried out for all the species occurring in the reactions at the B3LYP/AUG-cc-pVDZ level of theory, by use of the polarizable continuum model (PCM). Vibrational frequency analysis was performed, and zero-point-energy (ZPE)-corrected total energies and Gibbs free energy changes at 298.15 K were obtained. The genuineness of the calculated transition states was confirmed by visually examining the vibrational modes and also by intrinsic reaction coordinate (IRC) calculations. The reaction between ONOOCO2- and guanine occurring through four different mechanisms leads to the formation of 8-oxoG or its anion, while the reaction between the same two species occurring through a different scheme leads to the formation of 8-nitroG-. It has been shown that the presence of a water molecule along with ONOOCO2- would not affect the reaction mechanisms significantly. Structures of the reactant complexes, product complexes and barrier energies involved in the reactions reveal that CO2 acts as a catalyst for the reaction between ONOO- and guanine. The cause of the catalytic action of CO2 is mainly due to intermediacy of the CO3 radical anion and NO2 radical into which ONOOCO2- is fragmented while reacting with guanine. The relative stabilities of the different product complexes suggest that the mutation caused by ONOO- in the presence of CO2 would mainly involve 8-oxoG.