A major objective of the proposed research is to synthesize and study ligand-bridged binuclear metal complexes that are designed to be useful analogs of selected metalloprotein core structures. Particular emphasis will be placed on imidazolate-bridged copper, zinc, and manganese systems since recent X-ray structural work on bovine superoxide dismutase (SOD) revealed that an imidazole group from histidine serves to bridge Cu(II) and Zn(II) in this enzyme. In addition, studies of sulfur-bridged complexes of iron, cobalt, nickel, and copper will be carried out, since thiolato-bridged chromophores of this kind are thought to comprise the important functional units at the active sites of a number of metalloproteins. The reactions of these ligand-bridged complexes with small molecule substrates such as superoxide ion (O2), carbon monoxide, nitric oxide, sulfur dioxide, nitrosonium cation, and alkyl isocyanides will be monitored. The molecule structures of selected ligand-bridged complexes will be determined by X-ray crystallography. The effects of ligand structure and the choice of metal ion on the chemical reactivity, redox, and electron transport properties of imidazolate-and thiolate-bridged complexes will be investigated using electrochemical and spectroscopic methods. Features of the enzyme mechanism of SOD will be evaluated using tritium exchange labelling techniques and through chemical studies in aprotic solvents. Fundamental knowledge of the mechanism of action of superoxide dismutase will complement recent biological work that has established its role in defending against pulmonary oxygen toxicity, paraquat toxicity, and chronic granulomatous disease.