This application seeks continued support for an established research program in bioinorganic chemistry directed at a detailed understanding of biologically relevant cluster clusters containing iron, sulfur, and molybdenum, vanadium, or nickel, various types of which are found at all levels of life. The field of this proposal is biomimetic inorganic chemistry, in which it is proposed to synthesize certain of the most complex metallocenters currently recognized in biology. These include the clusters found in nitrogenase and nickel-containing carbon monoxide dehydrogenase, which catalyse the reduction of dinitrogen to ammonia and the interconversion of carbon monoxide and carbon dioxide, respectively, and thus are major factors in the biological utilization of nitrogen, carbon, and oxygen. The main objectives are the P-cluster, molybenum- and vanadium-containing cofactors and the all-iron cofactor of nitrogenase, and the nickel- iron-sulfur catalytic center of carbon monoxide dehydrogenase. Original methods for the synthesis of these entities are proposed using cluster self-assembly, fragment condensation, and core rearrangement. New cluster species prepared in this work will be subjected to detailed physicochemical characterization and reactivity investigations with appropriate substrates. One premise of this work is that the step-by-step formation of these biological clusters implicates reactivity properties intrinsic to the reactants themselves. The research is intended to contribute to the broad and developing area of biosynthesis of metallocenters by showing what synthetic routes are actually feasible for cluster construction in the absence, and possibly in the presence, of proteins. The synthesis of accurate analogues thus may contribute to an understanding of the biosynthesis of native clusters, for which reaction pathways are slowly emerging but molecular steps are unknown.
The proposed research seeks chemical reactions potentially similar to those in living cells that form metal-sulfur-containing molecules of importance to life processes and public health. These processes include the formation of ammonia from atmospheric nitrogen, affording the nitrogen utilized in the formation of DNA and numerous other molecules of life, and of carbon monoxide from carbon dioxide in a process that helps maintain ambient carbon monoxide below toxic levels. The molecules to be prepared should contribute to an understanding of how nature9s catalysts for these processes area formed naturally.
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