DFT study of adenine-uracil base pair damage by OH radical

The hydrogen abstraction and addition reactions of OH radical with A center dot U base pair have been explored by using density functional theory (DFT) both in gas phase and in aqueous solution. Solvent effects were taken into consideration by using the polarized continuum model. All the reaction pathways are exothermic in energy, and the compounds in aqueous phase are more favorable than those in gas phase. The relative free energies of adducts in the addition reaction are lower than those obtained for products in hydrogen abstraction reaction. Among dehydrogenation reaction, the hydrogen abstractions from A(C2)center dot U and A(N6)center dot U sites are more favorable than those from A(C8)center dot U, A center dot U-C5, and A center dot U-C6 sites. In addition, hydroxylation at A(C8)center dot U, A center dot U-C5, and A center dot U-C6 sites are more probable than other investigated positions. The hydroxylation at A(H8)center dot U site is most favorable, and hydroxylation at A center dot U-C5 site is more preference than that at A center dot U-C6 site controlled by the kinetics factors. The data in both gas phase and water solution demonstrated that addition of OH radical to A center dot U-C5 and A center dot U-C6 sites are more thermodynamically and kinetically favorable than abstracting the hydrogen atom form A center dot U-C5 and A center dot U-C6 sites. The phenomena are in agreement with the experimental observations. Copyright (C) 2015 John Wiley & Sons, Ltd.