Oxidation of guanine in DNA yields the nucleobase damage product 8-oxoguanine (8-oxoG), whose further oxidation gives other more stable products. In the present study, the mechanism for the deamination of 8-oxoG with H(2)O, 2H(2)O, H(2)O/OH(-), and 2H(2)O/OH(-) and for protonated 8-oxoG (8-oxoGH(+)) with H(2)O has been investigated using ab initio calculations. All structures were optimized at RHF/6-31G(d), MP2/6-31G(d), and B3LYP with the 6-31G(d), 6-31+G(d), 6-31G(d,p), 6-31+G(d,p), and 6-31++G(d.p) basis sets. Energies were determined at the G3MP2 level of theory, and solvent calculations were performed using both the polarizable continuum model (PCM) and the solvation model on density (SMD). Intrinsic reaction coordinate calculations were performed to characterize the transition states on the potential energy surface. Thermodynamic properties (ΔE, ΔH, and ΔG), activation energies, enthalpies, and Gibbs free energies of activation were also calculated for each reaction investigated. All pathways yield an initial tetrahedral intermediate and, in the final step, an intermediate that dissociates to products via a 1,3-proton shift. At the G3MP2 level of theory, deamination with H(2)O/OH(-) was found to have an overall activation energy of 187, 176, and 156 kJ mol(-1) for the gas phase, PCM, and SMD, respectively, which are ∼50 kJ mol(-1) lower than with H(2)O only. These barriers can be compared to those for the reaction of 8-oxoGH(+) with H(2)O of 248 kJ mol(-1) in the gas phase and 238 kJ mol(-1) in aqueous solution (PCM). The lowest overall activation energies (G3MP2) are for the deamination of 8-oxoG with 2H(2)O/OH(-), 134 kJ mol(-1) in the gas phase and 129 kJ mol(-1) with PCM.
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