The synthesis and characterization of a variety of new metalloporphyrin compounds is proposed. The work will emphasize, but will not be limited to, iron porphyrinate derivatives. Most classes of compounds proposed for study are related to hemoprotein derivatives, which carry out a wide range of biological functions including oxygen utilization and transport, electron transport, drug metabolism and other enzymatic processes. Another class of derivatives are related to species of photosynthetic reactions. The methods of three-dimensional X-ray crystal structure determination will be applied to define molecular structures and various detailed aspects of metalloporphyrin stereochemistry. Other methodologies to be applied, as appropriate, include characterization of magnetic properties by bulk temperature-dependent susceptibility and electron paramagnetic resonance (EPR) measurements, Mossbauer, vibrational and UV-vis spectroscopy, and electrochemical properties. The research objectives, stated in the broadest terms, are to achieve a synthesis of the structural and physical properties of metalloporphyrins, particularly as these relationships pertain to an understanding of hemoprotein-based biological processes. In part, this will be accomplished by establishing possible stereochemical features of a metalloporphyrin group and its biological environment and to model specific prosthetic group behavior of selected hemoproteins. Such studies are expected to provide understanding of how protein structures could modulate metalloporphyrin geometry and how a wide variety of biological processes can be carried out with the same fundamental iron protoporphyrin IX unit. Iron porphyrinates to be studied include synthetic analogues of bis(histidine)-ligated cytochromes b and c to examine how features such as axial ligand orientation affect their electronic structure and oxidation-reduction properties. Another significant research objective is the exploration of electronic interactions in metalloporphyrins; detailed studies will examine coupling in systems with potential intra- and/or intermolecular pathways. Included in such studies are species with oxidized or reduced porphyrin cores in which eta-radical spin-coupling is significant. These species are important to understanding catalytically important intermediates of high-valent hemoprotein systems such as catalases and peroxidases. Other systems with electronic coupling interactions to be explored include systems with the coupled metal ions separated in well-defined ways (bridging ligands or electrostatic interactions).
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