Copper ions interact or react with molecular oxygen in many copper- containing enzymes. Dioxygen is reduced to water at the type 3 site in the multicopper """"""""blue"""""""" oxidases, O2 reacts reversibly with Cu(I) in hemocyanin, and dioxygen is required in hydroxylation reactions mediated by tyrosinase and dopamine beta-hydroxylaste. Cu-dioxygen adducts are also implicated in systems where DNA fragmentation occurs and associated with other abnormal biological conditions. To understand the nature of these biological processes, it is important to study well defined Cu-O2 complexes. These need to be examined in order to elucidate those factors governing their formation, structural types, spectral and physical characteristics and reactivity trends. We have recently discovered a number of Cu-dioxygen adducts; one of these is the first example in which the binding and oxidation state of coordinated dioxygen is confirmed by vibrational spectroscopy. The proposed studies will focus on the characterization of the properties and reactivity of discrete Cu-dioxygen complexes. Specifically, we will: 1) carry out structural determinations by x-ray crystallography and EXAFS spectroscopy. Other physical methods to be employed are IR, Raman, electronic (UV-Vis), NMR and EPR spectroscopy, and electrochemical technique. It is also important to deduce equilibrium binding constants and kinetics of reaction in order to relate the structure, stability and reactivity of Cu-O2 species. 2) determine the reactivity of Cu-dioxygen adducts. Reactions with reagents capable of distinguishing the nucleophilicity vs. electrophilicity, the redox characteristics (1 or 2-electron reagent) and structure of these compounds will be carried out. Phenols, catechols and other biomimetic substrates will also be reacted with the complexes in order to determine the nature of the products and to relate reactivity to variations in Cu-dioxygen type. 3) design, synthesize and characteristize new Cu-dioxygen complex systems in order to increase the thermal stability of the compounds and to develop biomimetic systems. These studies will include attaching complexes to polymer or ion-exchange support media, and using cyclodextrin derivitaves as binucleating ligands. The latter system (and others) will enable substrates to approach the Cu-dioxygen active center with increased affinity so as to increase the efficiency and selectivity of reaction.
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