Biologically active metal-independent superoxide dismutase mimics

Biochemistry. 1990 Mar 20;29(11):2802-7. doi: 10.1021/bi00463a024.


Superoxide dismutase (SOD) is an enzyme that detoxifies superoxide (O2.-), 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 nitroxides that 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 O2.- ranging from 1.1 x 10(3) to 1.3 x 10(6) M-1 s-1. These SOD mimics protect mammalian cells from damage induced by hypoxanthine/xanthine oxidase and H2O2, although they exhibit no catalase-like activity. In addition, the nitroxide SOD mimics rapidly oxidize DNA-FeII 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 activity and/or interception of an electron from redox-active metal ions they protect cells from oxidative stress and may have use in basic and applied biological studies.

MeSH terms

  • Animals
  • Cells, Cultured
  • Chemical Phenomena
  • Chemistry
  • Cricetinae
  • Cytochrome c Group / metabolism
  • DNA / metabolism
  • Electron Spin Resonance Spectroscopy
  • Ferrous Compounds / metabolism
  • Nitrogen Oxides / metabolism
  • Oxazoles
  • Oxidation-Reduction
  • Superoxide Dismutase* / genetics


  • Cytochrome c Group
  • Ferrous Compounds
  • Nitrogen Oxides
  • Oxazoles
  • oxazolidine
  • DNA
  • Superoxide Dismutase