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

Abstract

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.

Surface ligand controls silver ion release of nanosilver and its antibacterial activity against <em>Escherichia coli</em>

“…The level of MDA production in each exposure group was quantified according to the specific absorbance of adducts at 532 nm. 22 8-Oxoguanine determination using liquid chromatography-mass spectrometry/mass spectrometry (lc-Ms/Ms)…”

“…The peroxidation of lipid by active free oxidative radicals could produce oxidized products of aldehydes, such as MDA and 4-hydroxyl nonenal (4-NHE), resulting in the loss of cell membrane integrity and even damage on cell structure. 22,40 MDA, as a common biomarker, was quantitatively measured in E. coli treated with Cit@AgNPs and Ag + to evaluate the potential lipid peroxidation. The results in Figure 5A show that Cit@AgNPs and Ag + treatments slightly increase MDA levels in E. coli, indicating the existence of lipid peroxidation due to oxidative damage.…”

Unusual Kinetic Isotope Effects of Deuterium Reinforced Polyunsaturated Fatty Acids in Tocopherol-Mediated Free Radical Chain Oxidations

“…The bis-allylic methylene group of polyunsaturated lipids is particularly vulnerable to radical attack, [13][14][15] and a recent strategy to diminish lipid peroxidation in vivo is based on deuterium substitution at the reactive center. 16 Incubation of yeast with small amounts of 11,11-D 2 linoleic acid (11,11-D 2 -Lin), for example, increases the resistance of yeast to oxidative stress, 17 and the same isotopically reinforced fatty acid diminishes neurodegeneration in a mouse model of Parkinson's disease.…”

Chemistry of Lipid Peroxidation Products and Their Use as Biomarkers in Early Detection of Diseases

“…reported that 7-dehydrocholesterol is the most oxidizable lipid molecule, and that the consequences of its extreme reactivity on human health should be clarified 20,21 .…”