Revised Manuscript Received October 27, 1989 abstract: Superoxide dismutase (SOD) is an enzyme that detoxifiessuperoxide (Of), a potentially toxic oxygen-derived species. Attempts to increase intracellular concentrations of SOD by direct application are complicated because SOD, being a relatively large molecule, does not readily cross cell membranes. We have identified a set of stable nitroxidesthat possess SOD-like activity, have the advantage of being low molecular weight, membrane permeable, and metal independent, and at pH 7.0 have reaction rate constants with Of ranging from 1.1 X 103 to 1.3 X 106 M_1 s" 1. These SOD mimics protect mammalian cells from damage induced by hypoxanthine/xanthine oxidase and H202, although they exhibit no catalase-like activity.

In addition, the nitroxide SOD mimics rapidly oxidize DNA-Fe11***** and thus may interrupt the Fenton reaction and prevent formation of deleterious OH radicals and/or higher oxidation states of metal ions. Whether by SOD-like activityand/or interception of an electron from redox-active metal ions they protect cells from oxidative stress andmay have use in basic and applied biological studies.