The catalysis of multi-electron redox reactions is a fundamental problem that has been solved in certain biological systems through the agency of multimetallic enzymes (cytochrome c oxidase, laccase, and nitrogenase). The detailed mechanisms by which these metalloenzymes function are still obscure. Our research is directed towards the synthesis of functional biomimetic catalysts for the electrochemical reduction of dioxygen to water (a 4e- process), nitrogen to ammonia (a 6e- process), and the oxidation of hydrogen (a 2e- process). Recently we have developed several functional models for the active site in cytochrome c oxidase. These complexes reduce O2 by 4e- at pH. Our complex that is structurally closest to "the real thing," is the best catalyst. By studying the electrocatalytic reduction of dioxgen in lipid layers under conditions of slow electron delivery, we have shown that Cub and an appended tyrosine (Try-244) is necessary to afford selective 4e reduction of dioxygen at physiological potentials. By using our functional model we are exploring the action of hydrogen sulfide interacting with cytochrome c oxidase. Hydrogen sulfide can produce a state of hibernation in animals, probably by its interaction with cytochrome c oxidase. Understanding this process could lead to drugs that induce hypoxia and may have many medical applications.

(1) "Role of a Distal Pocket in the Catalytic O2 Reduction by Cytochrome c Oxidase Models Immobilized on Interdigitated Array Electrodes," J.P. Collman; R.A. Decreau; H. Lin; A. Hosseini; Y. Yang; A. Dey; T.A. Eberspacher, Proc. Natl. Acad. Sci. U.S A, Early Edition, (2009).

(2) "Catalytic Reduction of O2 by Cytochrome c Using a Synthetic Model of Cytochrome c Oxidase," J.P. Collman; S. Ghosh; A. Dey; R.A. Decreau; Y. Yang, J. Am. Chem. Soc.., 131, 5034-5035 (2009).

(3) "A Functional Nitric Oxide Reductase Model," J.P. Collman; Y. Yang; A. Dey; R.A. Decreau; S. Ghosh; T. Otah; E.I. Solomon, Proc. Natl. Acad. Sci. U. S. A., 105, 15660-15665 (2008).

(4) "Functional Biomimetic Models for the Active Site in the Respiratory Enzyme Cytochrome c oxidase," J.P. Collman; R.A. Decréau, Chem. Comm, 5065-5076 (2008).

(5) "Interaction of nitric oxide with a functional model of cytochrome c oxidase," J.P. Collman; A. Dey; R.A. Decreau; Y. Yang; A. Hosseini; E.I. Solomon; T.A. Eberspacher, Proc. Natl. Acad. Sci. U. S. A, 155, 9892-9896 (2008).

(6) "Single-Turnover Reaction in a Cytochrome c Oxidase Model Bearing a Tyr244 Mimic," R.A. Decréau; J.P. Collman; Y. Yan; J. Yoon; E.I. Solomon., J. Am. Chem. Soc., 129, 5794 - 5795 (2007).

(7) "A Cytochrome c Oxidase Model Catalyzes Oxygen to Water Reduction Under Rate-Limiting Electron Flux," J.P. Collman; N.K. Devaraj; R.A. Decréau; Y. Yang; Y. Yan; W.Ebina; T.A. Eberspacher; C.E.D. Chidsey, Science, 315, 1565-1568 (2007).

(8) "Active-Site Models of Bacterial Nitric Oxide Reductase Featuring Tris-Histidyl and Glutamic Acid Mimics: Influence of a Carboxylate Ligand on FeB Binding and the Heme Fe/FeB Redox Potential," J.P. Collman; Y. Yan; J. Lei; P.H. Dinolfo, Inorganic Chemistry, 45, 7581-7583 (2006).

(9) "Single-turnover intermolecular reaction between a FeIII-superoxide-CuI cytochrome c oxidase model and exogeneous Tyr244 mimics," J.P. Collman; R.A. Decreau; C. Sunderland,J. Chem. Comm., 3894-3896 (2006).