DESCRIPTION: This is a competitive renewal of R01 GM38401-24 to continue Dr. Scheidt's long standing leadership role in the synthesis and characterization of new metalloporphyrin compounds. The work emphasizes, but is not limited to, the iron porphyrinate compounds and their derivatives. Most of the classes of compounds that are proposed for study are related to the goal of developing a detailed understanding of hemoproteins and the chemistry of their prosthetic groups. A second major area of focus is on the class of porphyrinate derivatives which are related to the prosthetic groups central to photosynthetic reactions. The primary method to be employed is three-dimensional X-ray crystal structure determination, with the goal of defining the molecular structures and various detailed functional aspects of metalloporphyrin stereochemistry. Through an extensive list of world-class collaborators, other methodologies to be applied to this quest include the characterization of magnetic properties by bulk temperature-dependent susceptibility and electron paramagnetic resonance (EPR) measurements, Mossbauer spectroscopy, vibrational and UV-vis-NIR spectroscopy, electrochemical properties, and molecular mechanics calculations. The overall stated research objectives are to achieve a synergistic understanding of the structural and physical properties of metalloporphyrins, particularly as these relationships pertain to an understanding of hemoprotein-based biological processes. The general paths include establishing possible stereochemical features of a metalloporphyrin group in its biological environment and modeling specific prosthetic group behavior of selected hemoproteins through theoretical calculations. 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 by nature by using the same fundamental iron protoporphyrin IX prosthetic group. Iron porphyrinates to be studied include synthetic analogs of bis(istidine)-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 pi-radical spin-coupling is significant. These species are important to understanding catalytically important intermediates of high-valent hemoprotein systems such as the catalases, peroxidases, and cytochromes P-450. Other systems with electronic coupling interactions to be explored include systems with the coupled metal ion separated in well-defined ways through bridging ligands or porphyrin-porphyrin pi-pi interaction.