Influence of hydrogen bonds on the reaction of guanine and hydroxyl radical: DFT calculations in C(H+)GC motif

Abstract

A comprehensive theoretical investigation was performed to illuminate the influence of hydrogen bonds (H-bonds) on the obscure reaction of a hydroxyl radical (HO˙) and guanine (G) by selecting the building block of parallel triplex DNA, C(H⁺)GC, as the model. By mapping the energy profiles for addition and hydrogen abstraction reactions, the favorable pathway is predicted. The results reveal that in the C(H⁺)GC context, barrierless hydrogen abstraction from N2 of G leading to a neutral radical G(N2–H)˙ appears to become significant, but electrophilic attack by HO˙ on C8 of G resulting in 8-oxoG is the most thermodynamically favorable course. This shows a strong structural dependence due to the context constrained by the H-bond, which is dramatically different from the situation in unencumbered G. More interestingly, it proves that the stability order of resulting adduct radicals is not altered by H-bonding, but the activity for possible sites of the hydroxylation reaction changes. The significant influence of the H-bond on elementary reactions involved in the reaction is emphasized in the C(H⁺)GC context but is not restricted to the H-abstraction reaction. It is greatly anticipated that the present study could provide thoughtful insights into the vague hydroxyl radical-induced oxidation chemistry.