5-S-Lipoylhydroxytyrosol, a Multidefense Antioxidant Featuring a Solvent-Tunable Peroxyl Radical-Scavenging 3-Thio-1,2-dihydroxybenzene Motif
5-S-Lipoylhydroxytyrosol, a Multidefense Antioxidant Featuring a Solvent-Tunable Peroxyl Radical-Scavenging 3-Thio-1,2-dihydroxybenzene Motif
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DOI：
10.1021/jo401522q
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发表时间：
2013-10-04
影响因子：
3.6
通讯作者：
d'Ischia, Marco
中科院分区：
文献类型：
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作者：
Amorati, Riccardo;Valgimigli, Luca;d'Ischia, Marco
5-S-脂酰羟基酪醇（1）是一组新型生物启发多重防御抗氧化剂的母体成员，本文显示其具有强效的过氧化氢自由基清除特性，这些特性以溶剂依赖性方式由与活性邻二酚部分相邻的硫中心控制。相对于母体羟基酪醇（HTy），1被证明是极性溶剂（乙腈）中模型自氧化过程的更有效的抑制剂，这是由于对与溶剂的氢键的不利影响的敏感性较低。用EPR自由基平衡技术测定了叔丁醇中的O-H键离解能（BDE），结果表明，BDE在正丁醇中存在一个平衡态。1.5 kcal/mol，相对于HTy，1的值较低。在良好的一致性，DFT计算的BDEOH使用明确的甲醇分子模拟溶剂的影响预测一个1.2千卡/摩尔较低的值为1相对于HTy。迫使几何形状的S-R基团与芳香环共面导致计算的BDEOH值急剧下降，这表明潜在的比参考抗氧化剂α-生育酚更高的活性，这取决于微观非均相环境中的几何约束。这些结果指出，硫取代作为一种方便的工具，以合理和可预测的方式定制邻苯二酚衍生物的链断裂抗氧化剂性质。
5-S-Lipoylhydroxytyrosol (1), the parent member of a novel group of bioinspired multidefense antioxidants, is shown herein to exhibit potent peroxyl radical scavenging properties that are controlled in a solvent dependent manner by the sulfur center adjacent to the active o-diphenol moiety. With respect to the parent hydroxytyrosol (HTy), 1 proved to be a more potent inhibitor of model autoxidation processes in a polar solvent (acetonitrile), due to a lower susceptibility to the adverse effects of hydrogen bonding with the solvent. Determination of O-H bond dissociation enthalpies (BDE) in t-butanol by EPR radical equilibration technique consistently indicated a ca. 1.5 kcal/mol lower value for 1 relative to HTy. In good agreement, DFT calculations of the BDEOH using an explicit methanol molecule to mimic solvent effects predicted a 1.2 kcal/mol lower value for 1 relative to HTy. Forcing the geometry of the S-R group to coplanarity with the aromatic ring resulted in a dramatic decrease in the computed BDEOH values suggesting a potentially higher activity than the reference antioxidant a-tocopherol, depending on geometrical constrains in microheterogeneous environments. These results point to sulfur substitution as an expedient tool to tailor the chain breaking antioxidant properties of catechol derivatives in a rational and predictable fashion.