Department of Chemistry and Biochemistry, Mount Allison University, Sackville, New Brunswick, Canada.
Chem Res Toxicol. 2013 Mar 18;26(3):399-409. doi: 10.1021/tx300486r. Epub 2013 Feb 28.
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.
三种 2-甲基-3-羟基吡啶酮，1-甲基-1-（4-甲氧基）苯基-2-和 1-（4-二甲基氨基）苯基-3，被发现不具有强抗氧化性质，与文献报道相反。与已知的酚类抗氧化剂 2,2,5,7,8-五甲基-6-羟基色满（PMHC）或 2,6-二叔丁基-4-甲氧基苯酚（DBHA）相比，这些吡啶酮在溶液中对由偶氮二异丁腈（AIBN）引发的苯乙烯或甲基油酸的过氧自由基没有表现出强烈的断链抗氧化活性。吡啶酮 2 在枯烯中的抗氧化活性较弱，kinh=1.3×10(3)M(-1)s(-1)，而 2,6-二叔丁基-4-甲基苯酚（BHT）的 kinh=4.3×10(3)M(-1)s(-1)。在 0.50 M 十二烷基硫酸钠（SDS）胶束的水脂质分散体中，由偶氮双（2-脒基丙烷）盐酸盐（ABAP）引发的脂质过氧化中，这些吡啶酮不是有效的抗氧化剂，2 既不能抑制 pH 7.0 或 4.0 时的甲基油酸过氧化，而 BHT 则有效地抑制了氧的摄取。此外，在胶束中抑制亚油酸过氧化时，2 与 Trolox 联合使用并没有表现出任何协同抗氧化作用。在水脂质分散体中，吡啶酮是重金属离子（特别是铜）引发反应的有效预防性抗氧化剂；例如，2 阻止了 SDS 胶束中 Cu 离子引发的亚油酸过氧化。特别是 2 和 3 在防止酚类抗氧化剂 PMHC 或 Trolox 加入到 Cu(2+)引发的过氧化中迅速产生的促氧化效应“尖峰”方面非常有效。提出了一种解释这种促氧化剂效应的方法。
