MECHANISTIC PROBES FOR ENZYME-CATALYZED OXIDATIONS

酶氧化自由基中间体的机制探针将是 开发并应用于酶的氧化反应， 化学模拟物 一类新的酶的碳自由基探针 烃的氧化是基于芳基的开环 取代的环丙基原基;这些预期是 超敏感探针 开环反应的动力学和机理 将在本报告中研究探针可能形成的自由基。 P.I.的实验室，也将通过酶模拟物氧化探针。 的 探针及其可能的氧化产物将提供给 研究单加氧酶的合作小组，包括 来自微生物的可溶性非血红素甲烷单加氧酶， 微粒体细胞色素P-450依赖性单加氧酶。 的组合 模拟和酶的研究，预计将导致一个清晰的描绘， 各种酶催化烃氧化反应的共同点 涉及到分子氧。 氮自由基反应动力学规模类似于目前 碳自由基的存在将得到发展。 中性和带电 氮自由基将由美国国家原子能机构开发的前体产生， P.L.的基团，反应动力学将由直接 （激光闪光）和间接（竞争）方法。 的动力学尺度 氮自由基反应预计是重要的机制， 酶对胺氧化作用的研究。 这些研究最终可能 导致新的单胺氧化酶抑制剂用于治疗 抑郁症和帕金森病。

Mechanistic probes for radical intermediates in enzyme oxidations will be developed and applied in oxidation reactions by enzymes and their simple chemical mimics. A new class of carbon radical probes for enzyme oxidations of hydrocarbons are based on the ring opening of aryl substituted cyclopropylcarbinyl radicals; these are expected to be hypersensitive probes. The kinetics and mechanisms of ring openings of the radicals that could be formed from the probes will be studied in the P.I.'s laboratory as will oxidations of the probes by enzyme mimics. The probes and their possible oxidation products will be supplied to collaborating groups for studies with monooxygenase enzymes including soluble non-heme methane monooxygenases from microorganisms and microsomal cytochrome P-450 dependent monooxygenases. The combination of mimic and enzyme studies is expected to result in a clear delineation of the common aspects of the various enzyme catalyzed hydrocarbon oxidations that involve dioxygen. A nitrogen radical reaction kinetic scale similar to that which currently exists for carbon radicals will be developed. Neutral and charged nitrogen radicals will be produced from precursors developed by the P.l.'s group, and the kinetics of reactions will be determined by direct (laser flash) and indirect (competition) methods. The kinetic scale of nitrogen radical reactions is expected to be important for mechanistic studies of amine oxidations by enzymes. Such studies might ultimately result in new monoamine oxidase inhibitors for the treatment of depression and Parkinsons disease.