Chauvin Jean-Philippe R, Haidasz Evan A, Griesser Markus, Pratt Derek A
Department of Chemistry and Biomolecular Sciences , University of Ottawa , 10 Marie Curie Pvt. , Ottawa , Ontario , Canada . Email:
Chem Sci. 2016 Oct 1;7(10):6347-6356. doi: 10.1039/c6sc01434h. Epub 2016 Jun 23.
Polysulfides are important additives to a wide variety of industrial and consumer products and figure prominently in the chemistry and biology of garlic and related medicinal plants. Although their antioxidant activity in biological contexts has received only recent attention, they have long been ascribed 'secondary antioxidant' activity in the chemical industry, where they are believed to react with the hydroperoxide products of autoxidation to slow the auto-initiation of new autoxidative chain reactions. Herein we demonstrate that the initial products of trisulfide oxidation, trisulfide-1-oxides, are surprisingly reactive 'primary antioxidants', which slow autoxidation by trapping chain-carrying peroxyl radicals. In fact, they do so with rate constants ( = 1-2 × 10 M s at 37 °C) that are indistinguishable from those of the most common primary antioxidants, hindered phenols, such as BHT. Experimental and computational studies demonstrate that the reaction occurs by a concerted bimolecular homolytic substitution (S), liberating a perthiyl radical - which is 16 kcal mol more stable than a peroxyl radical. Interestingly, the (electrophilic) peroxyl radical nominally reacts as a nucleophile - attacking the of the trisulfide-1-oxide - a role hitherto suspected only for its reactions at metal atoms. The analogous reactions of trisulfides are readily reversible and not kinetically competent to inhibit hydrocarbon autoxidation, consistent with the longstanding view that organosulfur compounds must be oxidized to afford significant antioxidant activity. The reactivity of trisulfides and their oxides are contrasted with what is known of their shorter cousins and predictions are made and tested with regards to the reactivity of higher polysulfides and their 1-oxides - the insights from which may be exploited in the design of future antioxidants.
多硫化物是多种工业产品和消费品中的重要添加剂，在大蒜及相关药用植物的化学和生物学中也占据显著地位。尽管它们在生物环境中的抗氧化活性直到最近才受到关注，但在化学工业中，它们长期以来一直被认为具有“二级抗氧化剂”活性，据信它们会与自氧化产生的氢过氧化物反应，从而减缓新的自氧化链反应的自动引发。在此，我们证明三硫化物氧化的初始产物三硫化物-1-氧化物是出人意料的活性“一级抗氧化剂”，它们通过捕获链携带过氧自由基来减缓自氧化。事实上，它们的反应速率常数（37℃时为1 - 2×10⁹ M⁻¹s⁻¹）与最常见的一级抗氧化剂受阻酚（如BHT）的速率常数并无差异。实验和计算研究表明，该反应通过协同双分子均裂取代（S）发生，释放出一个过硫自由基，该自由基比过氧自由基稳定16千卡/摩尔。有趣的是，（亲电的）过氧自由基名义上作为亲核试剂反应——攻击三硫化物-1-氧化物的硫原子——这一作用此前仅在其与金属原子的反应中被怀疑。三硫化物的类似反应很容易逆转，在动力学上无法抑制烃类的自氧化，这与长期以来的观点一致，即有机硫化合物必须被氧化才能提供显著的抗氧化活性。将三硫化物及其氧化物的反应活性与已知的较短链类似物进行了对比，并对更高阶多硫化物及其1-氧化物的反应活性进行了预测和测试——从中获得的见解可能会被用于未来抗氧化剂的设计。
