This award in the Inorganic, Bioinorganic, and Organometallic Chemistry program supports research in bioinorganic chemistry and in metal clusters by Dr. Richard H. Holm of the Chemistry Department, Harvard University. Four lines of investigation will be pursued. In the first topical area, accurate minimal synthetic representations of the catalytic sites of the enzymes dimethylsulfoxide reductase, nitrate reductase, and formate dehydrogenase will be examined. Pathways for enzymatic transformations and the factors contributing to the feasibility of these pathways will be explored. The second area of research involves biologically related nickel and iron chemistry pertinent to the enzyme hydrogenase. Tetracysteinyl cyclic peptides designed to stabilize the thiolate-bridged arrangement of the two metals will be prepared. The kinetics of dihydrogen uptake and evolution will be studied in the resulting model compounds. The third area includes synthesis of a peroxide-bridged heme-copper species and investigation of magnetic coupling between iron and copper, an imporant property of heme-copper oxidases. Interactions of porphyrin-containing iron-copper complexes with peroxide and the enzyme inhibitor cyanide will also be studied. Finally, mesoscale metal chalcogenide clusters will be synthesized and characterized. The clusters will contain rhenium and sulfur or selenium and will be linked by bridging interactions.
Metals play important roles in the activity of a wide range of enzymes, but factors controlling their activity are not entirely understood. Here compounds modeling a number of enzymes will be synthesized and the effect of structural and electronic changes on mode of action will be studied. One potential outcome is a molecular level description of the basis of cyanide toxicity in aerobic organisms. Graduate students involved in the investigation will learn a wide variety of advanced spectroscopic methods and will benefit from involvement in a program that includes collaborators at other institutions.
