MODES OF OXYGEN ACTIVATION BY CYTOCHROME P-450

哺乳动物肝脏完成的生物羟化过程 微粒体细胞色素P-450将被仔细研究。总体目标将是 为了确定氧的活化和插入的详细机制 底物。细胞色素P-450催化两种氧活化模式， 一种利用NADPH/O2，另一种利用有机过氧化氢。特定的 目的是确定活性氧中间体的化学特性。 在这两种模式中，建立两者之间的机制关系。一种新的 机械论的提议，即准芬顿机制，将在这里得到检验 项目。更长期的目标包括开发一种预测模型 外源物质的氧化和血红素-氧化学的一般理论。 纯化、均一的细胞色素P-450将被制备和使用。最基本的 实验方法将推论的化学特性 活性氧因其对选定底物的行为而产生。该方法 将是物理有机化学和具体的实验将寻求 确定自由基的存在，内部氢同位素的选择性， 立体化学，以及活性氧的化学特性。

The process of biological hydroxylation as accomplished by mammalian liver microsomal cytochrome P-450 will be scrutinized. The general objective will be to determine the detailed mechanism of oxygen activation and insertion into substrate. Two modes of oxygen activation are catalyzed by cytochrome P-450, one utilizing NADPH/O2 and the other utilizing organic hydroperoxides. Specific aims are to determine chemical identities for the activated oxygen intermediates in both modes and to establish the mechanistic relation between the two. A new mechanistic proposal, the quasi-Fenton mechanism, will be tested in this project. Longer range goals include the development of a predictive model for the oxidation of xenobiotics and a general theory of heme-oxygen chemistry. Purified, homogeneous cytochrome P-450 will be prepared and used. The basic experimental methods will be the inference of chemical characteristics of the activated oxygen from its behavior toward selected substrates. The approach will be that of physical organic chemistry and specific experiments will seek to determine the presence of radicals, internal hydrogen isotope selectivity, stereochemistry, and the chemical characteristics of the activated oxygen.