Tautomeric equilibria in 8-oxopurines: implications for mutagenicity.

Free-radical-induced DNA damage by ionizing radiation leads to a number of oxidized purines, of which 7H-8-oxoguanine (8OG) and 7H-8-oxoadenine (8OA) are predominant and known to cause an appreciable amount of cellular damage. A detailed quantum mechanical study at various levels of theory in both the gas phase and in an aqueous solution has been carried out in order to assess the tautomeric preferences of the bases. The calculated energies of various plausible tautomers suggest that at higher levels of ab initio theory with inclusion of electron correlation, the 8-keto-6-enolic form of 8-oxoguanine (8OG2) would predominate over the 6,8-diketo form (8OG1) in the gas phase whereas the 6-amino-8-keto form (8OA1) predominates over the other possible tautomers of 8-oxoadenine. Aqueous solvation, however, changes the gas-phase order for 8-oxoguanine, 8OG1 turning out to be the major tautomeric species in an aqueous medium. The estimated free energies of hydration by polarized continuum models are indicative that the mutagenically significant amounts of minor tautomeric forms of 8-oxoguanine and 8-oxoadenine exist in the aqueous phase and might be held responsible for inducing transversional as well as transitional mutations.