DESCRIPTION (provided by applicant): Proteins that contain copper ions in their active sites represent a large and functionally significant class of metallobiomolecules that play important roles in a wide range of life processes. The functional diversity of copper proteins is matched by variability in active site geometric, electronic structural, and spectroscopic features. A molecular level understanding of structure/function relationships is desirable, but despite extensive research efforts many issues remain unresolved regarding the detailed mechanisms of action and underlying chemistry of copper protein active sites. The aim of the proposed research is to obtain essential chemical insights into copper protein structure and function and to develop novel and fundamentally significant copper chemistry through the synthetic modeling approach, wherein low molecular weight complexes designed to replicate metalloprotein active site properties are characterized and their reactivity studied. The specific aims of the proposed research are to: 1. Understand the interrelationships of the variable structures and redox behaviors of type 1 copper electron transfer sites found in numerous metalloproteins. Perturbations of copper-thiolate complex properties and electron transfer kinetics of ruthenium and/or rhenium/copper-thiolate assemblies will be examined. 2. Obtain fundamental insight into dioxygen activation by monocopper sites in biologically important proteins such as dopamine beta-monooxygenase and galactose oxidase through studies of the O2 reactivity of copper complexes of hindered bidentate N-donor ligands, phenolate chelates, and ligands with attached remote oxidants like those operative in catalysis by copper enzymes. 3. Investigate dioxgyen activation by the tricopper active sites of the ubiquitous and biologically significant multicopper oxidases by using a novel stepwise synthetic strategy involving the reaction of 1:1 Cu/O2 species with dicopper complexes. 4. Understand the underlying chemistry of the novel (mu-sulfido)tetracopper active site of nitrous oxide reductase, an important participant in the global nitrogen cycle. Parallel studies will be performed of various mono- and disulfido-bridged dicopper complexes and of specifically designed tetracopper clusters.