Reactions of water with radical cations of guanine, 9-methylguanine, 2′-deoxyguanosine and guanosine: keto–enol isomerization, C8-hydroxylation, and effects of N9-substitution

Abstract

The reactions of D₂O with radical cations of guanine (9HG˙⁺), 9-methylguanine (9MG˙⁺), 2′-deoxyguanosine (dGuo˙⁺) and guanosine (Guo˙⁺) were studied in the gas phase, including measurements of reaction cross sections over a center-of-mass collision energy (E_col) range from 0.1 to 2.0 eV and computation of reaction pathways at DLPNO-CCSD(T)/aug-cc-pVTZ//ωB97XD/6-31+G(d,p). Reaction efficiencies of all radical cations are well below unity (∼2% of collision rate), despite there being exoergic pathways. For each reactant ion, the energetically most favorable product channel corresponds to the formation of water complexes; however, this channel accounts for only 5% of the total cross section at the lowest E_col and becomes negligible at high E_col due to short complex lifetimes. The dominant product channel is H/D exchange that appears to be complex-mediated at low E_col, but switches to a direct mechanism and accompanies keto–enol isomerization of the guanine moiety when E_col increases. C8-hydroxylation, a minor yet the most biologically important channel, was observed for 9HG˙⁺; and its mechanism was elucidated in the presence of single and double water molecules, of which the second water eliminates the barrier for C8-addition via a proton shuttle mechanism. All reactions show strong dependence on radical structures, with overall reactivity being 9HG˙⁺ ≫ 9MG˙⁺ > dGuo˙⁺ ≈ Guo˙⁺. The reaction dynamics of 9HG˙⁺ and 9MG˙⁺ with water were simulated at E_col = 0.1 eV using ωB97XD/6-31+G(d), to reveal complex formation at the early stage of the reaction and the effects of N9-substitution. Trajectory results suggest that the lack of a W9 complex (water bonded to N9–H) is responsible for the reduced reactivity of N9-substituted radical cations; but the relatively long-lived W16 complexes (water bonded to N1–H and C6–O) of dGuo˙⁺ and Guo˙⁺ may enhance keto–enol isomerization.