Department of Biochemistry and Organic Chemistry, Uppsala University, Box 576, SE-751 23 Uppsala, Sweden.
J Org Chem. 2010 Feb 5;75(3):716-25. doi: 10.1021/jo902226t.
The synthesis of 3-pyridinols carrying alkyltelluro, alkylseleno, and alkylthio groups is described together with a detailed kinetic, thermodynamic, and mechanistic study of their antioxidant activity. When assayed for their capacity to inhibit azo-initiated peroxidation of linoleic acid in a water/chlorobenzene two-phase system, tellurium-containing 3-pyridinols were readily regenerable by N-acetylcysteine contained in the aqueous phase. The best inhibitors quenched peroxyl radicals more efficiently than alpha-tocopherol, and the duration of inhibition was limited only by the availability of the thiol reducing agent. In homogeneous phase, inhibition of styrene autoxidation absolute rate constants k(inh) for quenching of peroxyl radical were as large as 1 x 10(7) M(-1) s(-1), thus outperforming the best phenolic antioxidants including alpha-tocopherol. Tellurium-containing 3-pyridinols could be quantitatively regenerated in homogeneous phase by N-tert-butoxycarbonyl cysteine methyl ester, a lipid-soluble analogue of N-acetylcysteine. In the presence of an excess of the thiol, a catalytic mode of action was observed, similar to the one in the two-phase system. Overall, compounds bearing the alkyltelluro moiety ortho to the OH group were much more effective antioxidants than the corresponding para isomers. The origin of the high reactivity of these compounds was explored using pulse-radiolysis thermodynamic measurements, and a mechanism for their unusual antioxidant activity was proposed. The tellurium-containing 3-pyridinols were also found to catalyze reduction of hydrogen peroxide in the presence of thiol reducing agents, thereby acting as multifunctional (preventive and chain-breaking) catalytic antioxidants.
描述了带有烷基碲、硒和硫基团的 3-吡啶醇的合成，以及它们抗氧化活性的详细动力学、热力学和机理研究。在水/氯苯两相体系中测定它们抑制偶氮引发的亚油酸过氧化的能力时，含有碲的 3-吡啶醇很容易被水相中含有的 N-乙酰半胱氨酸再生。最好的抑制剂比α-生育酚更有效地猝灭过氧自由基，抑制时间仅受硫醇还原剂可用性的限制。在均相相中，苯乙烯自氧化的抑制常数 k(inh)对于过氧自由基的猝灭高达 1 x 10(7) M(-1) s(-1)，因此超过了包括α-生育酚在内的最好的酚类抗氧化剂。含有碲的 3-吡啶醇可以通过 N-叔丁氧羰基半胱氨酸甲酯在均相相中定量再生，N-乙酰半胱氨酸甲酯是 N-乙酰半胱氨酸的脂溶性类似物。在过量硫醇存在下，观察到催化作用模式，类似于两相体系中的模式。总体而言，带有 OH 基团邻位的烷基碲部分的化合物比相应的对位异构体具有更高的抗氧化活性。使用脉冲辐射热力学测量探索了这些化合物高反应性的起源，并提出了它们不寻常抗氧化活性的机制。还发现含碲的 3-吡啶醇在硫醇还原剂存在下能够催化过氧化氢的还原，从而作为多功能（预防和链断裂）催化抗氧化剂发挥作用。
