Abstract：
Hydrogen sulfide (H2S), an endogenous signaling molecule, is known to play a pivotal role in neuroprotection, vasodilation, and hormonal regulation. To further explore the biological effects of H2S, refined donors that facilitate its biological delivery, especially under specific (patho) physiological conditions, are needed. In the present study, we demonstrate that ortho-substituted, aryl boronate esters provide two unique and distinct pathways for H2S release from thioamide-based donors: Lewis acid-facilitated hydrolysis and reactive oxygen species (ROS)-induced oxidation/cyclization. Through a detailed structure-activity relationship study, donors that resist hydrolysis and release H2S solely via the latter mechanism were identified, which have the added benefit of providing a potentially useful heterocycle as the lone byproduct of this novel chemistry. To highlight this, we developed an ROS-activated donor (QH642) that simultaneously synthesizes a benzoxazole-based fluorophore en route to its H2S delivery. A distinct advantage of this design over earlier self-reporting donors is that fluorophore formation is possible only if H2S has been discharged from the donor. This key feature eliminates the potential for false positives and provides a more accurate depiction of reaction progress and donor delivery of H2S, including in complex cellular environments.
摘要：
硫化氢(H2S),内源性信号分子，众所周知，在神经保护中起着关键作用，血管舒张,和荷尔蒙调节。为进一步探讨H2S的生物学效应,促进其生物递送的精制捐赠者，特别是在特定的(病理)生理条件下，是需要的。在本研究中,我们证明了邻位取代，芳基硼酸酯为从基于硫代酰胺的供体释放H2S提供了两种独特且不同的途径：路易斯酸促进的水解和活性氧（ROS）诱导的氧化/环化。通过详细的结构-活性关系研究，确定了仅通过后一种机制抵抗水解和释放H2S的供体，其具有提供潜在有用的杂环作为这种新型化学的单独副产物的额外益处。为了强调这一点，我们开发了一种ROS激活的供体（QH642），可同时合成基于苯并恶唑的荧光团，以输送H2S。这种设计相对于早期自我报告供体的明显优点是,只有当H2S已经从供体中排出时,才有可能形成荧光团。这一关键特征消除了假阳性的可能性，并提供了对反应进程和H2S供体输送的更准确描述，包括在复杂的蜂窝环境中。
