The biochemistry of manganese is important in many areas of metabolism and biological function. Manganese active sites involved in oxygen metabolism provide molecular mechanisms for defense against toxic oxygen metabolites (superoxide and peroxide) and thus have important clinical implications. The functions of these metalloenzyme active sites must be an expression of the special electronic structural features imposed on the complexes by the protein structure. By identifying the fundamental relations between electronic structure and reactivity, the origins of the chemistry of these highly evolved metal complexes will be revealed and important catalytic principles will be established. The research outlined in this proposal aims to contribute to this effort by developing spectroscopic and theoretical insights into the inorganic functional groups of manganese metalloenzymes. These functional groups represent essential aspects of the structure of the active site metal complex that defines its chemistry. We will explore the Mn-OH functional group in Mn superoxide dismutase, the mu-bridging oxo functional group in Mn catalase, investigate the nature of the reactive intermediates in the chemistry of the Mn complex of bleomycin, an antitumor antibiotic, and the structure and interaction of the multinuclear Mn cluster forming the oxygen evolving complex of photosynthesis. These studies will make use of a combination of powerful spectroscopic approaches including UV-visible-near IR optical absorption, circular dichroism (CD), low temperature, variable field magnetic circular dichroism (MCD) and low temperature electron paramagnetic resonance spectroscopies. The information contained in the spectra will be developed from a theoretical analysis of the electronic structures of Mn complexes. These studies on biological Mn complexes will be complemented by experimental and theoretical studies on structurally defined inorganic Mn complexes, providing essential calibration. This research is expected to contribute significantly to understanding the fundamental aspects of Mn metabolism through these and other studies aimed at exploring the diversity of Mn biomolecules and metalloregulatory functions of Mn in gene expression.
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