Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218, United States.
J Org Chem. 2021 Jan 1;86(1):868-877. doi: 10.1021/acs.joc.0c02412. Epub 2020 Dec 22.
Nitroxyl (HNO) has gained a considerable amount of attention because of its promising pharmacological effects. The biochemical mechanisms of HNO activity are associated with the modification of regulatory thiol proteins. Recently, several studies have suggested that hydropersulfides (RSSH), presumed signaling products of hydrogen sulfide (HS)-mediated thiol (RSH) modification, are additional potential targets of HNO. However, the interaction of HNO with reactive sulfur species beyond thiols remains relatively unexplored. Herein, we present characterization of HNO reactivity with HS and RSSH. The reaction of HS with HNO leads to the formation of hydrogen polysulfides and sulfur (S), suggesting a potential role in sulfane sulfur homeostasis. Furthermore, we show that hydropersulfides are more efficient traps for HNO than their thiol counterparts. The reaction of HNO with RSSH at varied stoichiometries has been examined with the observed production of various dialkylpolysulfides (RSSSR) and other nitrogen-containing dialkylpolysulfide species (RSS-NH-SR). We do not observe evidence of sulfenylsulfinamide (RS-S(O)-NH) formation, a pathway expected by analogy with the known reactivity of HNO with thiol.
硝酰（HNO）由于其有前途的药理学作用而引起了相当大的关注。HNO 活性的生化机制与调节硫醇蛋白的修饰有关。最近，有几项研究表明，水合过硫化物（RSSH），假定是硫化氢（HS）介导的硫醇（RSH）修饰的信号产物，是 HNO 的另一个潜在靶标。然而，HNO 与除硫醇以外的活性硫物种的相互作用仍相对未被探索。本文介绍了 HNO 与 HS 和 RSSH 的反应性特征。HS 与 HNO 的反应导致多氢硫化物和硫（S）的形成，这表明其在磺酰硫氢化物稳态中可能具有作用。此外，我们表明水合过硫化物比其硫醇对应物更有效地捕获 HNO。已经以不同的化学计量比检查了 HNO 与 RSSH 的反应，观察到各种二烷基多硫化物（RSSSR）和其他含氮二烷基多硫化物（RSS-NH-SR）的生成。我们没有观察到亚磺酰亚磺酰胺（RS-S（O）-NH）形成的证据，这是一种与 HNO 与硫醇的已知反应类似的预期途径。
