X-Ray and Chemical Studies of Metalloporphyrins

这项建议的主要重点是发展与结构属性有关的基本知识 金属卟啉对其物理性质的影响，特别是铁衍生物的物理性质，特别是作为 这些都涉及到对基于血红素蛋白的生物过程的理解。该方法利用 分子结构的测定，通常是用X射线衍射法，以及相关的详细结构 其他测量属性的特征，并提供足够数量的示例，以确保 结论。在以前的工作中强调的物理性质包括不寻常的电子 结构、包括自旋态和自旋-自旋耦合在内的磁性和光谱性质 包括电子顺磁共振(EPR)和穆斯堡尔谱学，提供了基本的 对低分子量物种和血红素蛋白都有用的信息。我们现在是 将这种方法扩展到同步加速器--核共振振动光谱(NRVS) 用基于辐射的方法测量位于中心的铁化合物的振动光谱 许多生物分子。NRVS比拉曼或IR更有选择性，也更全面 光谱学，允许检测其他方法不可见的模式。大多数化合物将是 所研究的是与执行广泛的生物功能的血球蛋白衍生物有关 包括氧气利用、储存和运输、基于气体的信号、电子传输、药物 新陈代谢和其他酶过程。我们正在使用和开发NRVS以了解 血红素络合物振动模式的详细性质。这些振动测量可以 提供独特的信息，因为定向单晶测量可以参考详细的 分子结构特征。在我们最初的工作中，我们强调了对飞机外的识别 铁--配体振动对理解铁-咪唑键的性质是至关重要的 血红素和小气态配体与铁中心的缔合/解离。卟啉铁酸盐可用于 包括一些六配位的衍生物，[Fe(POR)(XO)(Im)](XO=O2，CO，NO)，in 为了研究相反配体改变时Fe-Im振动的变化，对 了解血红蛋白氧结合协作性和基于气体的信号转导问题。功能障碍 神经退行性变、中风、高血压等多种疾病状态。 从胃肠疾病到勃起功能障碍和心脏病。我们现在提议延长我们的 以一种新颖、复杂的方式进行定向单晶测量的实验。在这个实验中，我们 将检查作为分子特征的函数的面内振动光谱的各向异性； 理论预测和实验偏差表明，与 了解键合特征和计算可以获得。与温度相关的NRVS 将在选定的系统上进行测量，以进一步探索这些系统的动力学问题 包括一氧化氮和氧气系统的分子。压力的影响将被调查 通过测量压力高达8 Gpa的NRVS谱。只要有可能， 这些测量将在定向晶体样品上进行。

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.