Problems in Bioinorganic and Oxygen Atom Transfer Chemistry

Harvard University, Cambridge MA

Investigators

Abstract

This award by the Inorganic, Bioinorganic and Organometallic Chemistry program supports research by Prof. Richard H. Holm of Harvard University focused on molybdenum/tungsten hydroxylases and oxotransferases. The catalytic centers contain mononuclear Mo or W atoms bound to one or two pterin-dithiolene ligands (often called molybdopterin). The experimental approach involves the synthesis of low molecular weight representations or analogs of the catalytic sites of enzymes, which are fully characterized before being studied in reactivity investigations. The natural ligand is represented by a synthetic dithiolene, which functions as an ene-1,2-dithiolate when bound to molybdenum or tungsten and closely simulates the electronic environment engendered by the pterin-dithiolene. Through analog systems, the project examines reactions of the enzymes nitrate reductase, formate dehydrogenase, arsenite oxidase, acetylene hydratase, sulfite oxidase, and aldehyde oxidase, among others. This involves the synthesis of new active site analogs in oxidized and reduced states, including uncommon monodithiolene complexes, and kinetics determinations with attendant evaluation of rate constants and activation parameters. Kinetic and other information is used to deduce probable mechanisms for the reactions investigated. Also under investigation are the synthesis and oxo transfer reactivity of the non-physiological metals niobium, tantalum, and rhenium in their higher oxidation states. The essential components of enzymes involved in global carbon, nitrogen, and sulfur cycles and catalyzing the transfer of a single oxygen atom will be studied through analog complexes. Some of these enzymes, such as the sulfite and xanthine oxidases, occur in humans; and their malfunction leads to significant health risks. Graduate and postdoctoral students will be trained in synthesis, characterization and mechanism and in regard to the interrelationships between model and biological systems.