At present the consensus is that superoxide radicals have both beneficial and deleterious effects upon the living cell. The superoxide radical and its """"""""active oxygen"""""""" derivatives have been found to be by-products of pollutants (ozone and high energy ionizing radiation), of certain toxic compounds (paraquat), and are intermediates in a number of biochemical reactions. The oxidative attack of such agents upon biochemical systems can lead to many ill effects, among others, structural damage to biological membranes and disfunction of the living cell. Good progress has been made in reaction studies of superoxide radicals (HO2/02-), hydroxyl radicals (OH) and singlet molecular oxygen (1-0-2) with biological compounds/systems in isolation. However, the species responsible for the observed deleterious effects when both superoxide radicals and hydrogen peroxide are present in a biological system has/have not been characterized yet. While the Haber-Weiss reaction was shown to be too slow in absence of metal catalysts to generate the very reactive OH radical under physiological conditions, generation of singlet molecular oxygen by O2- disproportionation is now ruled out. Evidence is accumulating which implicates transition metal cations in the deleterious effects either as catalysts or superoxide radical complexes. We have studied some reactions of superoxide and perhydroxyl (HO2) radicals by the accurate and convenient techniques of pulse radiolysis and continuous-flow and stopped-flow radiolysis/vacuum-UV photolysis. We propose to combine these techniques and biochemistry to carry out the following research: a) Studies of HO2/02- and their transition metal complexes with compounds of biological interest (e.g., membrane components, enzymes, cofactors, etc.). b) Study the diffusion of HO2/02- and their metal complexes into/through simple bilayer membranes. c) elucidate some reaction steps in superoxide dismutase (CuSOD, MnSOD) catalyzed disproportionation of 02-. d) Studies of enzyme activated H02/02- reactions. e) Studies of the reactivity of H02/02- reactions. e) Studies of the reactivity of H02/02- with compounds of biological interest. All reactions will be investigated on a quantitative basis with complete product analysis, essential for mechanistic studies.
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