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 RuII–aqua complex, [RuII(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 RuIV–peroxo complex, [RuIV(η2-O2)(η5-C5Me5)(bpy)]+, subsequent reactions were initiated by a RuIII–superoxo complex, [RuIII(η1-O2•–)(η5-C5Me5)(bpy)]+. We confirmed the plausible path for the homolytic cleavage of the O–O bond in [RuIII(η1-O2•–)(η5-C5Me5)(bpy)]+ to form a RuIV–oxo complex, [RuIV(O)(η5-C5Me5)(bpy)]+, with the activation free energy (ΔGa) of 12.2 kcal/mol. The subsequent oxidation of the substrate by [RuIV(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 [RuIII(η1-O2•–)(η5-C5Me5)(bpy)]+ must exceed the high energy in the transition state (31.7 kcal/mol), indicating that [RuIV(O)(η5-C5Me5)(bpy)]+ catalyzed the oxidation of the substrate as reactive species. Conversely, the Cp*-ligand oxidation, which induced catalyst degradation, requires ΔGa 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.