[4] Role of iron in oxygen radical reactions

The discovery of the enzymatic production of the superoxide (O2·-) radical and of the presence of superoxide dismutase (SOD) enzymes in aerobic cells led directly to the proposal that O2·- is a major factor in oxygen toxicity and that SOD constitutes an important defense against it. Systems generating the O2·- radical have been shown to have a number of damaging effects, some of which are summarized. The superoxide radical itself in organic solvents is a powerful base and nucleophile, which may have relevance to reactions taking place within the interior of cell membranes. In many cases, damage is decreased by addition not only of SOD but also of catalase, and it was proposed that O2·- and H2O2 can combine together directly to generate the highly reactive hydroxyl radical, OH·. Indeed, damage is often decreased by the scavengers of this radical, such as mannitol, sodium formate, and thiourea. In such experiments, a range of scavengers should be used and it ought to be possible to correlate the degree of protection that they offer with the known rate constants for reaction of the scavengers with OH·. Several authors proposed that the salts of transition metals could catalyze the generation of hydroxyl radical, although most direct evidence for this has come from work with iron salts.