A Functional Model for the Active Site of Cytochrome Oxidase Catalytically Reduces Oxygen to Water under Physiological Conditions

At physiological pH and potential, a synthetic model of the active site of the cytochrome c oxidase (CcO) enzyme catalyzes 4-electron oxygen reduction. This model is covalently attached to a self-assembled monolayer (SAM) on a gold electrode. The model has all the essential components of the CcO active site: an iron heme (" heme a3 ") with proximal imidazole ligand and a set of three distal imidazoles attached to copper (" Cu-b "). A phenol mimicking " tyrosine 244 " is attached to one of the distal imidazoles. All three redox-active components are required to minimize the production of partially reduced oxygen species during oxygen reduction. This functional model demonstrates how CcO itself can tolerate the NO hormone, known to diffuse through mitochondria. It is proposed that Cu-b delivers superoxide to Fe-bound NO in heme a3 to form peroxynitrite and nitrate, which then diffuse.