With this renewal award, the Organic and Macromolecular Chemistry Program continues its support of the work of Professor Ned A. Porter of the Department of Chemistry at Vanderbilt University in Nashville, TN. The research will extend the PI's investigations of the mechanism of oxidations in chemical and biochemical systems. In order to facilitate these mechanistic studies, a series of free radical clocks will be developed. These clocks will be used to measure the rates of reaction of peroxyl radicals with a variety of biologically relevant substrates. The technique will allow measurements over a wide range of rate constants. The chemistry of substituted pyridinols, a new class of antioxidants that appear to react with peroxyl radicals some 10 to 100 times faster than vitamin E, will be examined. A variety of these pyridinols will be evaluated as antioxidants in low-density lipoproteins, LDL, the peroxidation of which has been implicated the development of coronary artery disease. This research, which will involve students in a broadly interdisciplinary program, is expected to provide fundamental data that will contribute to our basic understanding of antioxidant chemistry and biology.