Pyridinones are not antioxidants as shown by kinetics of free radical autoxidation, but they prevent radical oxidations catalyzed by toxic heavy metals

Chem Res Toxicol. 2013 Mar 18;26(3):399-409. doi: 10.1021/tx300486r. Epub 2013 Feb 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / chemistry*
  • Antioxidants / pharmacology*
  • Chromans / chemistry
  • Chromans / pharmacology
  • Free Radicals / metabolism
  • Kinetics
  • Lipid Peroxidation / drug effects
  • Metals, Heavy / metabolism
  • Oxidants / metabolism
  • Oxidation-Reduction / drug effects*
  • Pyridones / chemistry*
  • Pyridones / pharmacology*

Substances

  • Antioxidants
  • Chromans
  • Free Radicals
  • Metals, Heavy
  • Oxidants
  • Pyridones
  • 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid