Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China.
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China; State Key Laboratory of Microbial Technology, Shandong University, Jinan, Shandong 250100, China.
Bioorg Med Chem Lett. 2021 Aug 15;46:128148. doi: 10.1016/j.bmcl.2021.128148. Epub 2021 May 28.
Hydrogen sulfide (HS), the third gaseous transmitter after CO and NO, is a double-edged sword in the human body. A specific concentration of HS can attenuate myocardial ischemia-reperfusion injury by preserving mitochondrial function, in contrast, cause illness, including inflammation and stroke. There are already some probes for the real-time monitoring of the level of HS in the biological environment. However, they have some disadvantages, such as phototoxicity, low sensitivity, and low quantum yield. In this research, by linking 4-dinitrophenyl-ether (DNP), a specific recognition group for HS, with a chemiluminophore 1,2-dioxetane, we designed and synthesized the probe SCL-1. To tackle the barrier that the traditional chemiluminescent group has a short emission wavelength and is not easy to penetrate deep tissues, an acrylonitrile electron-withdrawing substituent was installed to the ortho-position of the 1,2-dioxanol hydroxy group. According to the same design strategy as SCL-1, the probe SCL-2 was designed with the modified chemiluminescent group. Studies have shown that SCL-2 with electron-withdrawing acrylonitrile has higher luminescence quantum yield and high sensitivity than SCL-1, realizing real-time detection of HS in vitro and in vivo. The LOD of SCL-2 was 0.185 μM, which was the best among the currently available luminescent probes for detecting HS. We envisage that SCL-2 may be a practical toolbox for studying the biological functions of HS and HS-related diseases.
硫化氢（HS）是继 CO 和 NO 之后的第三种气态递质，是人体内的一把双刃剑。特定浓度的 HS 可以通过保护线粒体功能来减轻心肌缺血再灌注损伤，相反，会导致疾病，包括炎症和中风。已经有一些探针可用于实时监测生物环境中 HS 的水平。然而，它们存在一些缺点，如光毒性、低灵敏度和低量子产率。在这项研究中，我们通过将 4-二硝基苯醚（DNP）与发光体 1,2-二氧杂环乙烷连接起来，设计并合成了探针 SCL-1。为了解决传统发光基团发射波长短且不易穿透深层组织的障碍，我们在 1,2-二氧杂环乙烷羟基的邻位安装了丙烯腈吸电子取代基。根据与 SCL-1 相同的设计策略，我们设计了带有修饰发光基团的探针 SCL-2。研究表明，带有吸电子丙烯腈的 SCL-2 具有更高的发光量子产率和高灵敏度，实现了 HS 的体外和体内实时检测。SCL-2 的 LOD 为 0.185 μM，是目前可用于检测 HS 的发光探针中最好的。我们设想，SCL-2 可能成为研究 HS 生物学功能和 HS 相关疾病的实用工具包。
