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

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 a-phenyl nitrones previously investigated as antioxidant therapeutics. A convenient H-1 NMR-based assay for assessing the potency of chain-breaking antloxidants 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 a-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 Voloclarskii 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 a-phenyl nitrones PBN, S-PBN, and NXY-059.