Esterase-Activated Perthiocarbonate Persulfide Donors Provide Insights into Persulfide Persistence and Stability
Esterase-Activated Perthiocarbonate Persulfide Donors Provide Insights into Persulfide Persistence and Stability
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DOI：
10.1021/acschembio.1c00805
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发表时间：
2022-01-13
影响因子：
4
通讯作者：
Pluth, Michael D.
中科院分区：
文献类型：
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作者：
Fosnacht, Kaylin G.;Cerda, Matthew M.;Pluth, Michael D.
过硫化物（RSSH）是与硫化氢（H2S）的生物学功能密切相关的重要活性硫物种（RSS）。然而，直接研究过硫化物是困难的，由于它们的亲核和亲电特性，这导致了不同RSS的平衡的产生。为了直接研究过硫化物的作用，特别是在生物系统中，需要过硫化物供体原位产生过硫化物。在这里，我们报告的合成酯酶激活的过硫代碳酸酯过硫化物捐助者和研究过硫化物释放的结构修饰的影响。虽然酯的空间体积没有显着改变过硫化物的释放动力学，增加硫醇的空间体积增加过硫化物的释放速率。此外，我们发现硫醇的空间体积和身份显着影响过硫化物的持久性。对来自过硫代碳酸盐的不同竞争反应途径的进一步机理研究揭示了可以递送多种RSS（即，H2S、COS或RSSH），这取决于过硫化物供体结构和活化剂特性。
Persulfides (RSSH) are important reactive sulfur species (RSS) that are intertwined with the biological functions of hydrogen sulfide (H2S). The direct study of persulfides is difficult, however, due to their both nucleophilic and electrophilic character, which leads to the generation of an equilibrium of different RSS. To investigate the effects of persulfides directly, especially in biological systems, persulfide donors are needed to generate persulfides in situ. Here, we report the synthesis of esterase-activated perthiocarbonate persulfide donors and investigate the effects of structural modifications on persulfide release. Although steric bulk of the ester did not significantly alter persulfide release kinetics, increased steric bulk of the thiol increased the persulfide release rate. In addition, we found that the steric bulk and identity of the thiol significantly impact persulfide persistence. Further mechanistic investigations into different competing reaction pathways from perthiocarbonates revealed that multiple RSS can be delivered (i.e., H2S, COS, or RSSH) depending on the persulfide donor structure and activator identity.