MECHANISTIC PROBES FOR ENZYME-CATALYZED OXIDATIONS

酶氧化中自由基中间体的机械探针将是 酶及其简易氧化反应的开发和应用 化学模拟。一类新型的碳自由基酶探针 碳氢化合物的氧化是以芳基的开环为基础的 取代的环丙基卡宾基；这些预计是 超灵敏探头。圆柱体开环的动力学和机理 可能从探针中形成的自由基将在 P.I.S实验室将通过酶模拟氧化探针。 探头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 微生物来源的可溶性非血红素甲烷单加氧酶和 微体细胞色素P-450依赖的单加氧酶。这两种技术的结合 模拟和酶研究有望清楚地描绘出 各种酶催化的碳氢化合物氧化反应的共同点 这涉及到氧气。 一个与目前类似的氮自由基反应动力学标度 存在的碳基将被开发出来。中性和带电 氮自由基将从由 P.L.‘S组，反应动力学将用直接法测定 (激光闪光灯)和间接(竞争)方法。其动力学标度 氮自由基反应被认为是重要的机械性反应 酶催化胺氧化反应的研究。这样的研究最终可能会 结果发现新的单胺氧化酶抑制剂用于治疗糖尿病 抑郁症和帕金森氏症。

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.