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 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.
Becker
David A
DA
Department of Chemistry, Florida International University, Miami, Florida 33199, USA. beckerd@fiu.edu
Ley
James J
JJ
Echegoyen
Luis
L
Alvarado
Robert
R
D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001555:Benzene Derivatives / Q000737:chemistry; D007700:Kinetics; D009589:Nitrogen Oxides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D010545:Peroxides / Q000737:chemistry; D012717:Sesquiterpenes
D000975:Antioxidants; D001555:Benzene Derivatives; D009589:Nitrogen Oxides; D010545:Peroxides; D012717:Sesquiterpenes; C015388:nitrones; C459743:stilbazulenyl nitrone; C049375:perhydroxyl radical; C015763:cumene; C007164:cumene hydroperoxide