Attacking mechanism of hydroxyl radical to DNA base-pair: density functional study in vacuum and in water

Abstract

Recently, the influence of radiation on human body has been recognized as a serious problem. In particular, highly reactive hydroxyl radicals *OH produced by the radiation react with DNA, resulting in a great damage on its structure and electronic properties. It is thus important to investigate the reaction mechanism of *OH to DNA for elucidating the initial damage in DNA induced by the radiation. In the present study, we search for transition states (TS) of the reaction between G-C/A-T base-pair and [Formula: see text] in vacuum and in water, by the density functional theory (DFT) calculations. At first, we obtain the stable structures for the dehydrogenated G-C and A-T, in which the hydrogen atom of NH2 group of G or A base is abstracted by [Formula: see text]. From the structures of the dehydrogenated as well as the natural base-pairs, the TS between these structures is searched for and the activation free energy (AFE) is estimated for the reaction. In vacuum, AFEs for the G-C and A-T are almost the same each other, while the stabilization energy by the reaction for G-C is about 4.9 kcal/mol larger than that for A-T, indicating that the population of the dehydrogenated G-C is remarkably larger than that of the dehydrogenated A-T in vacuum. On the other hand, in water approximated by the continuum solvation model, the AFE for A-T is 2.6 kcal/mol smaller than that for G-C, indicating that the reaction dehydrogenated by [Formula: see text] occurs more frequently for the solvated A-T base-pair than G-C.

DFT study on the attacking mechanisms of H and OH radicals to G-C and A-T base pairs in water

“…As a result, the AE and AFE are expected to be lowered significantly by the effect of solvation. Similar results were observed for the A-T + OH radical in our previous DFT study [17].…”

“…In the present study, SFE is defined as the difference in free energies for the reactant and the product structures, while AFE is defined as the difference in free energies for the reactant and the TS structures. The above mentioned process of DFT calculations is the same as that for the base pair + OH radical complexes [17].…”

“…From the comparison of the total energies evaluated for the optimized structures, the most stable structure of a base pair + H radical was determined. The same DFT calculations were carried out for a base pair + OH radical, as described in our previous papers [16,17]. …”

“…In the present study, to highlight the difference in the mechanism of the attacking reaction between OH and H radicals to DNA base pairs, we search for the transition states of the attacking mechanism between G-C or A-T and the radicals in water, using the same DFT calculations as in our previous study [17]. The tautomeric reactions of the base pairs attacked by OH or H radical are also investigated by the DFT method, in order to elucidate the effect of the radicals on the probability of the tautomeric reactions.…”

“…It was thus predicted that the OH radical can produce the isomerization of G and A bases, leading to spontaneous mutations in the DNA base sequence. In addition, to reveal the probability of the OH radical attacking reaction to G-C and A-T base pairs, we searched for the transition state (TS) of the reaction in vacuum and in water [17], using the DFT calculations. The results elucidated that the solvation around the base pair stabilizes the dehydrogenated structure of the base pair significantly, leading to an acceleration of the attacking reaction by the OH radical to the A-T base pair in water.…”