A Perspective on Free Radical Autoxidation: The Physical Organic Chemistry of Polyunsaturated Fatty Acid and Sterol Peroxidation

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 result of an oxidative stress. Cyclic peroindes, 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 extratheinnodynamic probes applied to the study of mechanism. A radical. clock permits the determination of free, radical.. propagation rate constants, and 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 the focus of a current research theme in the author's laboratory.