Theoretical Study of Intermediates in the Urate Oxidase Reaction

The energetics of the urate oxidase reaction has been studied employing HF, MP2, and DFT calculations. Gas-phase energies of possible urate oxidase reaction intermediates were calculated; radical species and dehydrourate had high relative energies while 5-hydroperoxy isourate was stable in the gas phase. Significant stabilization of the initial radical pair relative to reactants occurred in an aqueous environment, suggesting that oxidation of urate in water proceeds via a single-electron transfer pathway. The possibility of enzyme catalysis through proton abstraction from urate has been investigated by comparing the calculated properties of uric acid, urate monoanion, and urate dianion. Results indicate that ionization of uric acid is accompanied by polarization of the central carbon–carbon double bond and weaker binding of valence electrons.