Department of Chemistry, Brown University, Providence, RI 02912, USA.
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Angew Chem Int Ed Engl. 2024 Feb 5;63(6):e202317487. doi: 10.1002/anie.202317487. Epub 2024 Jan 2.
Hydrogen sulfide (H S) is an endogenous gasotransmitter that plays important roles in redox signaling. H S overproduction has been linked to a variety of disease states and therefore, H S-depleting agents, such as scavengers, are needed to understand the significance of H S-based therapy. It is known that elevated H S can induce oxidative stress with elevated reactive oxygen species (ROS) formation, such as in H S acute intoxication. We explored the possibility of developing catalytic scavengers to simultaneously remove H S and ROS. Herein, we studied a series of selenium-based molecules as catalytic H S/H O scavengers. Inspired by the high reactivity of selenoxide compounds towards H S, 14 diselenide/monoselenide compounds were tested. Several promising candidates such as S6 were identified. Their activities in buffers, as well as in plasma- and cell lysate-containing solutions were evaluated. We also studied the reaction mechanism of this scavenging process. Finally, the combination of the diselenide catalyst and photosensitizers was used to achieve light-induced H S removal. These Se-based scavengers can be useful tools for understanding H S/ROS regulations.
硫化氢(H₂S)是一种内源性气体递质,在氧化还原信号中发挥重要作用。H₂S 的过度产生与多种疾病状态有关,因此需要 H₂S 消耗剂(如清除剂)来了解基于 H₂S 的治疗的意义。众所周知,升高的 H₂S 可以诱导氧化应激,导致活性氧(ROS)形成增加,如 H₂S 急性中毒。我们探索了开发催化清除剂以同时去除 H₂S 和 ROS 的可能性。在此,我们研究了一系列基于硒的分子作为催化 H₂S/H₂O 清除剂。受硒氧化物化合物与 H₂S 高反应性的启发,测试了 14 个二硒化物/单硒化物化合物。鉴定出了几个有前途的候选物,如 S6。评估了它们在缓冲液中的活性,以及在含有血浆和细胞裂解物的溶液中的活性。我们还研究了这种清除过程的反应机制。最后,将二硒化物催化剂与光敏剂结合使用以实现光诱导的 H₂S 去除。这些基于 Se 的清除剂可作为理解 H₂S/ROS 调节的有用工具。