Catalytic Effect of Aqueous Solution in Water-Assisted Proton-Transfer Mechanism of 8-Hydroxy Guanine Radical.

Water-assisted proton-transfer process is a key step in guanine damage reaction by hydroxyl radical in aqueous solution. In this article, we quantitatively determine the solvent effect in water-assisted proton-transfer mechanism of 8-hydroxy guanine radical using combined quantum mechanics and molecular mechanism with an explicit solvation model. Atomic-level reaction pathway was mapped, which shows a synchronized two-proton-transfer mechanism between the assistant water molecule and 8-hydroxy guanine radical. The transition-state dipole moment is the largest along the reaction pathway, which electrostatically stabilizes the proton-transfer transition-state complex. The free-energy reaction barrier for this water-assisted proton-transfer reaction was calculated at 19.2 kcal/mol with the density functional theory/M08-SO/cc-pVTZ+/molecular mechanics level of theory. The solvent effect not only has a big impact on geometries, but also dramatically changes the energetics along the reaction pathway. Among the solvent effect contributions to the transition state, the solvent energy contribution is -28.5 kcal/mol and the polarization effect contribution is 19.9 kcal/mol. In total, the solvent effect contributes -8.6 kcal/mol to the free-energy barrier height, which means that the presence of aqueous solution has a catalytic effect on the reaction mechanism and enhances the proton-transfer reactivity in aqueous solution.