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Research |
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William A. Pryor, Ph. D. Louisiana State University - Biodynamics Institute |
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Organic Free Radical Research: Professor Pryor is a pioneer in the field of free radical research. His articles on the oxidation of hydrocarbons, on the reactions of sulfur compounds, on free radical initiators, and on vinyl polymerization are classical studies of the mechanisms of organic reactions. Professor Pryor's research group has supplied a significant portion of the quantitative data available on the reactions of radicals with hydrogen donors in solution. Pryor has reported rate patterns, analysis of polar, structural, and thermodynamic effects, and the detailed mechanistic analyses of the reactions of many radicals, including the hydrogen atom, methyl and phenyl radicals, substituted aryl radicals such as the para-nitrophenyl radical, and the thiyl radical. Professor Pryor's group was the first to study the kinetics of the reactions of hydrogen atoms in solution using hydrogen atoms produced by chemical rather than radiolytic methods. Pryor’s study of hydrogen atom transfer from thiols to radicals lead to a publication that remains the simplest experimental demonstration of the Westheimer effect (which explains why the maximum kinetic isotope effect is observed in the most symmetrical atom transfer reaction). That paper has been designated a Citation Classic by the Institute for Scientific Information (ISI) using computer-based citation analysis. In the 1960's, Dr. Pryor used a comparison of displacement reactions of ions with those of radicals on peroxides and disulfides. This research, which was the subject of a two-page news article in Chemical Engineering News, showed for the first time that radicals perform a “backside”, Walden inversion-like displacement reaction. This research still represents the best evidence for a Walden Inversion mechanism in displacement reactions by radicals. The polar rate effects observed in the reactions of neutral free radicals is a subject of longstanding interest to radical chemists. Pryor's conviction that fundamental insights into the causes of these polar effects can be obtained by an examination of Hammett equation correlations led his group to study and report many such systems. Pryor's group was the first to report positive Hammett rho values for the reactions of radicals, a finding that has considerable significance in interpretations of polar effects on radical reactions. His group also published methods for analyzing how free radical initiators decompose, including the use of viscosity effects on the rates of initiator decompositions to estimate the amount of cage return that initiators undergo. (Cage return is a process that limits initiator efficiency.) Free Radical Bio-Organic Research: Following the discovery of the enzyme superoxide dismutase in the mid 1960's, Dr. Pryor became the first free radical chemist to apply mechanistic insights from organic free radical chemistry to the study of radical reactions in a biological context. Dr. Pryor has a long-standing interest in the oxidants and toxins in smog (ozone, nitric oxide, nitrogen dioxide, peroxynitrites and peroxynitrates, and fine particulate matter). The Pryor group has published research on the reactive species in smog, including free radicals, that enter the air/lung interface to produce pathophysiological effects. Many sophisticated groups had been studying gas-phase smog chemistry, and an even greater number had been studying the effects of smog or individual smog constituents on animals. But no group had undertaken modeling the lung/air interface from the viewpoint of a chemist and attempting to describe the details of the reactions of species like ozone and the nitrogen oxides as they moved across this air/tissue barrier. Antioxidants: Dr. Pryor is an expert on the use of the antioxidant vitamins in human health. He was an organizer and speaker at the International Conference on vitamin E in 1982 [published as Vitamin E, Lubin & Machlin, editors, by the New York Academy of Sciences (NYAS) in 1982] as well as in 1989 [Vitamin E, Diplock, Machlin, Packer & Pryor, editors, NYAS, 1982]. He also was the organizer of the international conference on smoking and nutrition [Tobacco Smoking and Nutrition; Influence of Nutrition on Tobacco-Associated Health Risks, Diana & Pryor, editors, NYAS, 1993]. He was an organizer and chair of the international meeting on "Antioxidant Vitamins and $-Carotene in Disease Prevention" [published as a special issue of: Am. J. Clinical Nutrition, volume 53S, 1991]. Dr. Pryor was a member of the NIH Workshop on "Antioxidants in the Prevention of Human Atherosclerosis" [published in: Circulation 85: pages 2337-2344, 1992]. Dr. Pryor wrote the Commentary to the Food and Drug Administration on Vitamin Intake and the Risk of Cancer [US Government Printing Office, Dockets Branch, HFA-305, 1992]. He was a participant in the first FASEB “Controversy in Science” lectures in Washington D.C. in April 1996, where he and Harvard’s Dr. Meir Stampfer debated the wisdom of making a public health recommendation now on vitamin E. In June 1999, he wrote and submitted the vitamin industry’s Commentary for the Food and Drug Administration entitled: Vitamin E and Heart Disease, and in December 1999 he wrote the industry’s FDA Commentary entitled Antioxidant Vitamins and Cancer. Dr. Pryor’s research on smog and the oxidative stress it produces have led to some noteworthy contributions. For example, over the past decade he has provided a totally new insight into ozone’s toxicity. Ozone is ranked by the World Health Organization as the most important pollutant world-wide, and Dr. Pryor has been studying the mechanisms by which ozone produces its well-known inflammatory effects in the lung. Dr. Pryor showed that ozone was so reactive that it could not penetrate far enough into cells to directly cause the effects attributed to it. Instead, ozone reacts with the first reactive species that it contacts when it first enters the lung, and Dr. Pryor showed that these reactive species are unsaturated fatty acids that are present in the lung epithelial cell lining fluid (ELF). Thus, ozone reacts with unsaturated lipids in the ELF to produce lipid ozonation products (LOP), and it is these LOP that act as biological signal transduction species and relay the inflammatory and ancillary effects of ozone into deeper tissue strata than ozone itself can reach. This cascade theory of ozone toxicity is now well established. Dr. Pryor’s group has isolated LOP from pulmonary lavage of both rats and human volunteers exposed to ozone. No study of ozone can now be done without recognizing the importance of these LOP transduction species and considering their effects. In 1975, Dr. Pryor’s showed that the autoxidation of polyunsaturated fatty acids (PUFA) produces the important signaling molecules called prostaglandins (PG), but that this autoxidation leads to PG isomers with different (“unnatural”) stereochemistry from the PG produced by our PG-synthesizing enzymes. He predicted these iso-PG compounds would have biological activity in a paper became an ISI Citation Classic and is one of the 400 all-time most cited papers in the life sciences, as ranked by the Council of Biology Editors. In the past decade, a number of groups have demonstrated that iso-PG indeed are produced in animals and humans, and that several iso-PG compounds have very potent biological properties. Oxidative Stress Status (OSS) Measurement: Dr. Pryor has pioneered in the field of biomarkers for oxidative stress, a field he calls oxidative stress status (OSS) measurement. This field has great promise: if OSS could be measured in humans by reliable and inexpensive tests, then increases in OSS could be used to predict the onset of diseases such as cancer that put an oxidative burden on particular organs or on the entire organism. The OSS field currently is under intense development, with over a dozen firms marketing kits that measure OSS using blood, urine, or tissue samples. In 1982, Dr. Pryor showed that nitric oxide (NO) itself does not react with thiols to form nitrosothiols (RS-N=O); however, he showed that in the presence of oxygen , NO and thiols do react to form S-nitrosothiols. This publication preceded the current intense interest in nitric oxide and the recent awarding of the Nobel Prize for the discovery that nitric oxide is produced in our cells and acts as a hormone. Pryor’s paper is highly cited, since many scientists believe that S-nitrosothiols act as NO-carriers in our blood; this makes it critical that we understand the mechanism of S-nitrosation. Dr. Pryor’s group showed that peroxynitrite (the combination product of superoxide and nitric oxide) can both nitrate and nitrosate nucleophiles such as phenols, thiols and amines. It is known that NO is produced by many cell types and acts as a hormone or messenger molecule. However, NO also can cause pathological effects and has been liked to cancer formation. Dr. Pryor’s research group has been the forefront of the research on the mechanisms by which NO can cause biological damage, emphasizing the reaction of NO with superoxide forming peroxynitrite which is responsible for some of the pathological effects of NO. Dr. Pryor’s interests in the effects of the antioxidant vitamins on human health have led to his organizing and/or chairing many national and international meetings in this area. For example, he was an organizer and chair for: the international meeting on "Antioxidant Vitamins and $-Carotene in Disease Prevention" [published as a special issue of: Am. J. Clinical Nutrition, volume 53S, 1991]. Dr. Pryor was a member of the NIH Workshop on "Antioxidants in the Prevention of Human Atherosclerosis" [published in: Circulation 85: pages 2337-2344, 1992]. Dr. Pryor wrote the 1992 Commentary to the Food and Drug Administration on The Association between Vitamin Intake and the Risk of Cancer [US Government Printing Office, Dockets Branch, HFA-305, 1992]. He also, as mentioned above, wrote two new Commentaries to the FDA on antioxidants and diseases. He has continued to speak at international symposia on health, including plenary lectures at the FASEB meetings in 1996 and 1998. Dr. Pryor was the organizer of the Summer Gordon Conference “Free Radicals” and more recently of the Winter Gordon Conference “Oxy-Radicals in Biology and Medicine” and has served as Chair of both conferences
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