The proposed research seeks to elucidate the structure and function of iron-containing enzymes involved in a diverse range of biochemical reactions in the metabolism of nucleic acids, amino acids, fatty acids, biodegradation of aromatic compounds, and the biosynthesis of antibiotics. This research will be complemented by the study of high-valent synthetic complexes that can serve as structural or electronic models of the biological systems. The studies will focus on preparing and characterizing high-valent states of iron such as FeIV and FeV. It is also proposed to continue studies of yeast mitochondria, in particular of deletion mutants that produce aggregates of ferric iron which have been implicated in various neurodegenerative diseases. The experimental techniques employed are M""""""""ssbauer spectroscopy and electron paramagnetic resonance. The research plan also includes theoretical studies based on density functional theory calculations. Specifically the following systems will be studied: (1) Homoprotochatechuate 2,3 dioxygenase, three Rieske dioxygenases, and methane monooxygenase. (2) Synthetic mononuclear FeIV and FeV complexes as well as dinuclear FeIVFeIII, and FeIVFeIV complexes that can serve as structural and/or electronic models for the active sites of iron proteins. (3) Activators involving Fe-tetraamido macrocyclic ligands that have a demonstrated potential in green chemistry and have proven very potent in killing anthrax spores and eliminating pollutants from our water supply. (4) Intact mitochondria from S. cerevisiae, to identify conditions where the particular strength of M""""""""ssbauer spectroscopy can be employed to address important health problems.
Iron-containing enzymes involved in oxygen activation affect numerous chemical transformations in all biological systems. The proposed studies of these enzymes, coupled with investigations of novel synthetic complexes that mimic structural and functional features of the biological systems, will reveal how these important enzymes function. The research will be complemented by studies of a family of synthetic complexes that have proven to be effective in green chemistry and extremely potent in killing pathogens such as anthrax spores. ? ? ?
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