Theoretical Study of Guanine Oxidation Catalyzed by a Ruthenium Complex with an Oxygen Molecule

The oxidation of an aromatic ring in guanosine monophosphate by a Ru^II–aqua complex, [Ru^II(OH₂)(η⁵-C₅Me₅)(bpy)]⁺ (bpy = 2,2′-bipyridine), using O₂ gases in an aqueous solution has been reported (Takenaka et al. Chem. Asian J. 2018, 13, 3480–3184). However, its mechanism has not been sufficiently clarified to facilitate the design of optimal catalysts. To clarify the mechanism of aerobic oxidation catalyzed by Ru complexes, we employed density functional theory (DFT) calculations to analyze the oxidation of 9-methyl guanine, as a model of the substrate. Although the ligand–exchange reaction between the H₂O and O₂ molecules yielded a more stable Ru^IV–peroxo complex, [Ru^IV(η²-O₂)(η⁵-C₅Me₅)(bpy)]⁺, subsequent reactions were initiated by a Ru^III–superoxo complex, [Ru^III(η¹-O₂^•–)(η⁵-C₅Me₅)(bpy)]⁺. We confirmed the plausible path for the homolytic cleavage of the O–O bond in [Ru^III(η¹-O₂^•–)(η⁵-C₅Me₅)(bpy)]⁺ to form a Ru^IV–oxo complex, [Ru^IV(O)(η⁵-C₅Me₅)(bpy)]⁺, with the activation free energy (ΔG_a) of 12.2 kcal/mol. The subsequent oxidation of the substrate by [Ru^IV(O)(η⁵-C₅Me₅)(bpy)]⁺ facilitated the formation of an arenium-like intermediate to form the product compounds, where the energy in the transition state corresponding to the oxidation of the substrate is 21.5 kcal/mol. An additional reaction path for the oxidation of the substrate by [Ru^III(η¹-O₂^•–)(η⁵-C₅Me₅)(bpy)]⁺ must exceed the high energy in the transition state (31.7 kcal/mol), indicating that [Ru^IV(O)(η⁵-C₅Me₅)(bpy)]⁺ catalyzed the oxidation of the substrate as reactive species. Conversely, the Cp*-ligand oxidation, which induced catalyst degradation, requires ΔG_a of 21.4 kcal/mol to exceed the transition state. Overall, our DFT study offers insight into the reaction mechanism of aerobic oxidation involving inert chemical bonds, facilitating the design of appropriate catalysts for the reaction.