Theoretical Studies of Effect of Hydrogen Bond on Reaction of Hydroxyl Radicals and Guanine

Hydroxyl radical ((OH)-O-center dot) is a representative reactive oxygen species (ROS) with high oxidation potential, and could lead to the indiscriminate chemical modification on DNA causing oxidative damage. Interestingly, it has documented that the reaction of (OH)-O-center dot and guanine (G) reveals hydrogen bond-dependent fashion. Due to the highly specific binding of triplex forming oligonucleotide (TFO) to target duplex DNA leading to various surroundings of G, it makes triplex DNA as a prototype model to be examined. Inspired by this, by selecting the building block of antiparallel triplex DNA-GGC motif as the substrate, a comprehensive theoretical investigation was performed to illuminate the influence of hydrogen bond on the obscure reaction of (OH)-O-center dot and G by structural analysis, HOMO calculation and mapping the energy profiles for both addition and hydrogen abstraction reactions. Results reveal that the G located in TFO is more susceptible to the attack of (OH)-O-center dot. In GGC base pair, the neutral radical G(-H2)(center dot) could be formed by direct H-abstraction, where the participation of explicit water is adverse to H-abstraction from N2 of G. The electrophilic attack of (OH)-O-center dot to C8 of G resulting in 8-oxoG is the most favorable course due to the lowest energy barrier in comparison with H-abstraction pathway. And the stability of ion-pairs appears to significantly influence by hydrogen bond, which is less stable than the hydroxylated radicals different with free G. These results show clearly that the hydrogen bonds guide the reaction flux of (OH)-O-center dot and G.