Stilbazulenyl nitrone (STAZN): a nitronyl-substituted hydrocarbon with the potency of classical phenolic chain-breaking antioxidants

J Am Chem Soc. 2002 May 1;124(17):4678-84. doi: 10.1021/ja011507s.

Abstract

Stilbazulenyl nitrone (STAZN), 8, a nitronyl-substituted hydrocarbon, is a novel second-generation azulenyl nitrone with significantly enhanced potency as a chain-breaking antioxidant vs conventional alpha-phenyl nitrones previously investigated as antioxidant therapeutics. A convenient (1)H NMR-based assay for assessing the potency of chain-breaking antioxidants has shown that STAZN is ca. 300 times more potent in inhibiting the free radical-mediated aerobic peroxidation of cumene than is PBN and the experimental stroke drug NXY-059. Such levels of antioxidant efficacy are unprecedented among archetypal alpha-phenyl nitrone spin traps. Furthermore, STAZN outperforms such classical phenolic antioxidants as BHT and probucol and rivals the antioxidant potency of Vitamin E in a polar medium comprised of 80% cumene and 20% methanol. The Volodarskii electron-transfer mechanism involving the intermediacy of the STAZN radical cation has been implicated in attempts to ascertain the basis for the increased potency of STAZN over the three alpha-phenyl nitrones PBN, S-PBN, and NXY-059.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry*
  • Antioxidants / pharmacology
  • Benzene Derivatives / chemistry
  • Kinetics
  • Nitrogen Oxides / chemical synthesis*
  • Nitrogen Oxides / chemistry*
  • Nitrogen Oxides / pharmacology
  • Peroxides / chemistry
  • Sesquiterpenes

Substances

  • Antioxidants
  • Benzene Derivatives
  • Nitrogen Oxides
  • Peroxides
  • Sesquiterpenes
  • nitrones
  • stilbazulenyl nitrone
  • perhydroxyl radical
  • cumene
  • cumene hydroperoxide