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

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 (Ecol) 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 Ecol and becomes negligible at high Ecol due to short complex lifetimes. The dominant product channel is H/D exchange that appears to be complex-mediated at low Ecol, but switches to a direct mechanism and accompanies keto–enol isomerization of the guanine moiety when Ecol 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 Ecol = 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.