Electron-Induced Repair of 2'-Deoxyribose Sugar Radicals in DNA: A Density Functional Theory (DFT) Study.

In this work, we used ωB97XD density functional and 6-31++G** basis set to study the structure, electron affinity, populations via Boltzmann distribution, and one-electron reduction potentials (E°) of 2'-deoxyribose sugar radicals in aqueous phase by considering 2'-deoxyguanosine and 2'-deoxythymidine as a model of DNA. The calculation predicted the relative stability of sugar radicals in the order C4'• > C1'• > C5'• > C3'• > C2'•. The Boltzmann distribution populations based on the relative stability of the sugar radicals were not those found for ionizing radiation or OH-radical attack and are good evidence the kinetic mechanisms of the processes drive the products formed. The adiabatic electron affinities of these sugar radicals were in the range 2.6-3.3 eV which is higher than the canonical DNA bases. The sugar radicals reduction potentials (E°) without protonation (-1.8 to -1.2 V) were also significantly higher than the bases. Thus the sugar radicals will be far more readily reduced by solvated electrons than the DNA bases. In the aqueous phase, these one-electron reduced sugar radicals (anions) are protonated from solvent and thus are efficiently repaired via the "electron-induced proton transfer mechanism". The calculation shows that, in comparison to efficient repair of sugar radicals by the electron-induced proton transfer mechanism, the repair of the cyclopurine lesion, 5',8-cyclo-2'-dG, would involve a substantial barrier.