Synthesis and Redox Properties of Water-Soluble Asymmetric Trityl Radicals
Synthesis and Redox Properties of Water-Soluble Asymmetric Trityl Radicals
复制标题
水溶性不对称三苯甲基自由基的合成及氧化还原性能
DOI：
10.1021/acs.joc.1c00766
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发表时间：
2021-05-27
影响因子：
3.6
通讯作者：
Liu, Yangping
中科院分区：
文献类型：
--
作者：
Chen, Li;Wu, Lanlan;Liu, Yangping
四硫三芳基甲基（三酰基）自由基最近被证明能与生物氧化剂发生反应，包括谷胱甘肽（GSH）、抗坏血酸（Asc）和超氧阴离子自由基（O-2（中心点-））。然而，取代基如何影响三烷基自由基的反应性仍是未知的。本文合成了5个不对称三烷基自由基，并研究了它们与GSH、Asc和O-2（中心点-）的反应性。在有氧条件下，谷胱甘肽诱导硫醚衍生物（TSA）和亚甲基甘氨酸衍生物（TGA）的快速衰变，而含4-羧基苯基衍生物（TPA）的缓慢衰变。在厌氧条件下，GSH直接还原这些自由基的速率常数（k(GSH)）从TPA的1.8 × 10(-4) M-1 s（-1）到TGA的1.0 × 10(-2) M-1 s（-1）。此外，这些自由基还能与O-2（中心点-）反应，反应速率常数k（SO）从ET-01的1.2 × 10(3) M-1 s（-1）到TGA的1.6 × 10(4) M-1 s（-1）不等。令人惊讶的是，在有氧和厌氧条件下，这些自由基对Asc都是完全惰性的。此外，取代基对这些三烷基自由基的氧化还原电位有重要影响。这项工作表明，三甲基自由基的氧化还原特性强烈依赖于它们的取代基，对谷胱甘肽具有高稳定性的TPA在细胞内应用具有很大的潜力。
Tetrathiatriarylmethyl (trityl) radicals have been recently shown to react with biological oxidoreductants including glutathione (GSH), ascorbic acid (Asc), and superoxide anion radical (O-2(center dot-)). However, how the substituents affect the reactivity of trityl radicals is still unknown. In this work, five asymmetric trityl radicals were synthesized and their reactivities with GSH, Asc, and O-2(center dot-)-investigated. Under aerobic conditions, GSH induces fast decays for the thioether-(TSA) and Nmethyleneglycine-substituted (TGA) derivatives and slow decay for the 4-carboxyphenyl-containing one (TPA). Under anaerobic conditions, the direct reduction of these radicals by GSH also occurs with rate constants (k(GSH)) from 1.8 x 10(-4) M-1 s(-1) for TPA to 1.0 x 10(-2) M-1 s(-1) for TGA. Moreover, these radicals can also react with O-2(center dot-) with rate constants (k(SO)) from 1.2 x 10(3) M-1 s(-1) for ET-01 to 1.6 x 10(4) M-1 s(-1) for TGA. Surprisingly, these radicals are completely inert to Asc in both aerobic and anaerobic conditions. Additionally, the substituents exert an important effect on redox potentials of these trityl radicals. This work demonstrates that the redox properties of the trityl radicals strongly depend on their substituents, and TPA with high stability toward GSH shows great potential for intracellular applications.