Department of Chemistry and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235, USA.
J Org Chem. 2013 Apr 19;78(8):3511-24. doi: 10.1021/jo4001433. Epub 2013 Apr 9.
This Perspective describes advances from the author's laboratory on the free radical reactions of organic compounds with molecular oxygen. Polyunsaturated fatty acids (PUFAs) and sterols are particularly prone to undergo radical chain oxidation, and evidence suggests that this process, known as lipid peroxidation, occurs in vivo under a variety of conditions that are the result of an oxidative stress. Cyclic peroxides, hydroperoxides, and epoxy alcohols are major products formed from peroxidation, and the basic mechanisms of product formation are now reasonably well understood. These mechanisms include reversible addition of oxygen to carbon radicals, rearrangement and cyclization of allyl and pentadienyl peroxyl radicals, and homolytic substitution of carbon radicals on the peroxide bond. A physical organic approach to the problem of free radicals in biology and medicine is highlighted in this Perspective with stereochemical, kinetic, and extrathermodynamic probes applied to the study of mechanism. A radical clock permits the determination of free radical propagation rate constants, and 7-dehydrocholesterol, the immediate biosynthetic precursor of cholesterol, is found by this clock to be one of the most oxidizable lipids known. The consequences of the extreme reactivity of 7-dehydrocholesterol on human health is the focus of a current research theme in the author's laboratory.
这篇观点文章描述了作者实验室在有机化合物与分子氧的自由基反应方面的进展。多不饱和脂肪酸（PUFAs）和固醇特别容易发生自由基链式氧化，有证据表明，这种过程被称为脂质过氧化，在体内多种条件下都会发生，这些条件是氧化应激的结果。过氧化物、氢过氧化物和环氧化醇是过氧化形成的主要产物，产物形成的基本机制现在已经相当清楚。这些机制包括碳自由基与氧的可逆加成、烯丙基和戊二烯基过氧自由基的重排和环化，以及过氧化物键上碳自由基的均裂取代。本文以立体化学、动力学和超热力学探针为例，突出了一种生物学和医学中自由基问题的物理有机方法来研究机制。自由基钟可以确定自由基传播速率常数，通过这种时钟发现，7-脱氢胆固醇是胆固醇的直接生物合成前体，是已知最易氧化的脂质之一。7-脱氢胆固醇的极端反应性对人类健康的影响是作者实验室当前研究主题的焦点。
