The long term objective of the proposed research is the development of the fundamental coordination chemistry of copper ion as it pertains to the active site chemistry of proteins involved in O2-transport, O2- activation (e.g., monooxygenation, N-dealkylation) and O2-reduction. Through detailed studies of chemical model systems, a reasonable basis for hypothesis of biological structure and competency of intermediates can be made. There exists a paucity of information about Cu(I) coordination chemistry, and its reactions with O2/substrate. Our interests are in functional modeling, i.e., reactions of CuI/O2 and CuI/O2/substrate. The structures, spectroscopy and reactivity of possible intermediates such as Cu-O2-Cu, Cu-OOH, Cu-O-Cu and Cu-O are poorly understood. Systematic investigations using model compounds with varied, but known structure, ligation and associated CuII/CuI redox potential can lead to a better understanding of the biological transformations. The proposed research is divided into sub-projects, directed along various themes, questions, or chemical systems. We plan to study: (1) Cu-pterin interactions, to help elucidate the active site chemistry of Cu-phenylalanine hydroxylase. Chelating pterins will be used to study Cu/O2 reactions with reduced pterins and substrates. (2) Chemistry with tripodal tetradentate ligands, including dinucleating versions. Both Cu/O2 1:1 and 2:1 adducts should form and comparisons of structure, kinetics/thermodynamics and reactivity will provide fundamental information. (3) L2CuI/O2 + L' and LnCuI-X (X = CO, CN-, RNC, acetylene) chemistry with L as a biologically 'relevant' unidentate imidazole ligand. The latter compounds will help in developing spectroscopic probes for protein reduced Cu(I) ion. (4) The chemistry of side-on bound peroxo dinuclear complexes. Modified ligands will help probe structure and reactivity of these species, which are capable of effecting arene hydroxylation reactions. In addition to studies with 'endogenous' substrates, we will develop CuI/O2 chemistry using organic receptors for 'exogenous' substrates, such as cyclodextrins and those based on a diphenylglycoluril building block. (5) The chemistry of unsymmetrical dinuclear complexes will be developed. This is relevant to a number of Cu proteins, where one Cu ion (or cofactor) passes electrons to another which effects O2/substrate reactions. (6) Hydroperoxide-Cu interactions, which are involved in proteins such as dopamine b-hydroxylase and others. We will also investigate and compare structure, spectroscopy and reactivity of systems which are 'reductively activated', i.e., with Cu(I) complex reactions with ROOH. (7) Oxidative N-dealkylation chemistry using Cu-ligand systems observed to undergo such reactions; structures of intermediates and mechanism will be determined. (8) The chemistry of tri- and tetranuclear Cu complexes and their O2 reactions; Cu clusters occur in laccase & ascorbate oxidase and possibly in Cu methane monooxygenase. (9) O2-binding and reduction chemistry at porphyrin-Fe/Cu complexes, as structural/functional models for reactions occurring in cytochrome c oxidase.
Showing the most recent 10 out of 88 publications
