MODELS FOR CYTOCHROME P-450 HYDROXYLASES

这项研究是针对功能类似物的 酶家族细胞色素P-450。 这些混合功能的加氧酶 参与甾醇的生物合成和代谢， 解毒和生物活性的异生物质的有毒和 致癌产品。 本研究旨在提供 氧活化机制的分子背景， 转移，和自杀抑制期间的功能， 酶P-450。 新型金属卟啉化合物的合成与研究 作为各种有机底物氧化的催化剂。 P-450反应循环中间阶段的类似物 将被分离，表征，然后反应化学将 被研究。 这项工作将集中在特殊作用的半胱氨酸硫醇 配体和活化剂在异裂还原裂解 在P-450反应循环期间的分子氧。 各种电化学 技术与黄素介质将被用来模拟这两个 P-450反应中的关键单电子转移步骤 顺序 电化学、动力学测量、合成 有机和无机化学以及一系列光谱学 技术（1H NMR，IR，拉曼，MCD，穆斯堡尔，X-射线衍射 和EXAFS）将用于分子仿生研究。 亚铁血红素中心铁原子的钌类似物将被 在P-450化学的背景下制备和研究。

This research is directed towards functional analogues of the enzyme family cytochromes P-450. These mixed-function oxygenases are involved in sterol biosynthesis and metabolism, in drug detoxification, and in bioactivation of xenobiotics to toxic and carcinogenic products. The present studies are intended to provide a molecular background for the mechanisms of oxygen activation and transfer, and of suicide inhibition during the function of the enzymes P-450. Novel metalloporphyrin compounds will by synthesized and examined as catalysts for the oxygenation of various organic substrates. Analogues of ,he intermediate stages in the P-450 reaction cycle will be isolated, characterized, and then reaction chemistry will be studied. This work will focus on the special role of the cysteine mercaptide ligand and of activators in the heterolytic reductive cleavage of dioxygen during the P-450 reaction cycle. Various electrochemical techniques with flavin mediators will be used to mimic the two critical single-electron transfer steps in the P-450 reaction sequence. Electrochemistry, kinetics measurements, synthetic organic and inorganic chemistry and a range of spectroscopic techniques (1H NMR, IR, Raman, MCD, Mossbauer, X-ray diffraction and EXAFS) will be used in this molecular biomimetic research. Ruthenium analogues of the iron atoms in heme centers will be prepared and studied in the context of P-450 chemistry.