title: Pyridinones are not antioxidants as shown by kinetics of free radical autoxidation, but they prevent radical oxidations catalyzed by toxic heavy metals.
abstract: Three 2-methyl-3-hydroxypyridinones, 1-methyl-, 1; 1-(4-methoxy)phenyl-, 2; and 1-(4-dimethylamino)phenyl-, 3, were discovered not to possess strong antioxidant properties contrary to literature reports. These pyridinones were not active chain-breaking antioxidants toward peroxyl radicals generated from styrene or methyl oleate initiated by azobis-2-methylpropylnitrile (AIBN) in solution compared to known phenolic antioxidants, 2,2,5,7,8-pentamethyl-6-hydroxychroman (PMHC) or 2,6-di-tert-butyl-4-methoxyphenyl (DBHA). Pyridinone 2 exhibited weak antioxidant activity in cumene, kinh = 1.3 × 10(3) M(-1) s(-1), compared to 2,6-di-tert-butyl-4-methylphenol (BHT), kinh = 4.3 × 10(3) M(-1) s(-1). The pyridinones were not active antioxidants during lipid peroxidation initiated by azobis-2-amidinopropane·2HCl (ABAP) in aqueous-lipid dispersions of 0.50 M sodium dodecyl sulfate (SDS) micelles where 2 did not inhibit peroxidation of methyl oleate at pH 7.0 or 4.0, while BHT exhibited effective suppression of oxygen uptake. In addition, 2 did not exhibit any cooperative antioxidant effect in combination with Trolox during inhibited peroxidation of linoleic acid in micelles. Pyridinones were effective preventative antioxidants in aqueous-lipid dispersions against reactions initiated by heavy metal ions, notably copper; for example, 2 blocked peroxidation of linoleic acid initiated by Cu ions in SDS micelles. In particular, both 2 and 3 were active in preventing the rapid pro-oxidation effects, "spikes", of very rapid oxygen uptake when phenolic antioxidants PMHC or Trolox were added to peroxidations initiated by Cu(2+). A proposal is given to account for such pro-oxidant effects.
authors: Department of Chemistry and Biochemistry, Mount Allison University, Sackville, New Brunswick, Canada.
authors: Sharwatie
authors: S
authors: Ramsaywack
authors: Christopher M
authors: CM
authors: Vogels
authors: S Laurie
authors: SL
authors: Ricker
authors: Stephen A
authors: SA
authors: Westcott
authors: L Ross C
authors: LR
authors: Barclay
mesh_terms: D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D002839:Chromans / Q000737:chemistry / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D019216:Metals, Heavy / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects*; D011728:Pyridones / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D002839:Chromans; D005609:Free Radicals; D019216:Metals, Heavy; D016877:Oxidants; D011728:Pyridones; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid