X-Ray and Chemical Studies of Metalloporphyrins

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The main focus of this proposal is to develop basic knowledge that relates the structural properties of metalloporphyrins to their physical properties, especially those of iron derivatives, and particularly as these pertain to an understanding of hemoprotein-based biological processes. The approach utilizes the determination of molecular structure, typically by X-ray diffraction, and relating detailed structural features to other measured properties, with a sufficient number of examples to ensure generality of the conclusions. Physical properties that were emphasized in previous work included unusual electronic structures, magnetic properties including spin state and spin-spin coupling and spectral properties including electron paramagnetic resonance (EPR) and M¿ssbauer spectroscopy that provided fundamental information that are useful for both low-molecular weight species and hemoproteins. We are now extending this approach to Nuclear Resonance Vibrational Spectroscopy (NRVS), a synchrotron radiation-based method used to measure the vibrational spectrum of iron compounds that are at the center of many biomolecules. NRVS is both more selective and more comprehensive than Raman or IR spectroscopy, allowing for the detection of modes not visible by other methods. Most compounds to be studied are related to hemoprotein derivatives that carry out a wide range of biological functions including oxygen utilization, storage and transport, gas-based signaling, electron transport, drug metabolism, and other enzymatic processes. We are using and developing NRVS to understand the detailed nature of the vibrational modes of heme complexes. These vibrational measurements can provide unique information because oriented single crystal measurements can be referenced to detailed molecular structure features. In our initial work, we emphasized the identification of the out-of-plane iron--ligand vibrations that are vital to an understanding of both the nature of the Fe-imidazole bond in hemes and the association/dissociation of small gaseous ligands to the iron center. Iron porphyrinates to be studied include a number of six-coordinate derivatives, [Fe(por)(XO)(Im)] (XO = O2, CO, NO), in order to examine changes in the Fe--Im vibrations as the opposite ligand is changed, important for understanding issues in hemoglobin oxygen-binding cooperativity and gas-based signaling. Dysfunction of such signaling contributes to many disease states from neurodegeneration, stroke, hypertension, and gastrointestinal diseases to erectile dysfunction and heart disease. We now propose to extend our experiments to oriented single-crystal measurements in a novel, complex fashion. In this experiment, we will examine the anisotropy of the in-plane vibrational spectrum as a function of molecular features; both theoretical predictions and experiment deviations suggest that novel information that pertains to understanding bonding features and calculations can be obtained. Temperature-dependent NRVS measurements will be made on selected systems to further explore the dynamical issues of these molecules including both nitric oxide and dioxygen systems. The effect of pressure will be investigated through the measurement of the NRVS spectrum at pressures up to about 8 GPa. Whenever possible, these measurements will be made on an oriented crystal specimen.