On the evolution of one-electron-oxidized deoxyguanosine in damaged DNA under physiological conditions: a DFT and ONIOM study on proton transfer and equilibrium.

Different deprotonation paths of the radical cation formed by one-electron oxidation of 2'-deoxyguanosine (2dG) sites in DNA have been studied using Density Functional Theory (M05-2X/6-31+G(d,p)) and ONIOM methodology (M05-2X/6-31+G(d,p):PM6) in conjunction with the SMD model to include the solvent effects. Models of increased complexity have been used ranging from the isolated nucleoside to a three unit double-stranded oligomer including the sugar units, the base pairing with cytidine, and the phosphate linkage. The reported results correspond to aqueous solution, at room temperature, and pH = 7.4. Under such conditions it was found that the proton transfer (PT) within the base pair is a minor path compared to the PT between the base pair and the surrounding water. It was also found that the deprotonation of ground-state 2dG˙(+) sites mainly yields C centered radicals in the sugar unit, with the largest populations corresponding to C4'˙ and C5'˙, followed by C3'˙. The different aspects of the presented theoretical study have been validated with experimental results.