Saying NO to HS: A Story of HNO, HSNO, and SSNO.

Interactions between small inorganic molecules are fundamental to the understanding of basic reaction mechanisms and some of the initial processes of chemical evolution that preceded organic molecules and led to the origin of life. The kinetics of these processes are suitable for the fast generation of a variety of new chemical entities and the propagation of a cascade of chemical reactions, a property that is ideal for signaling purposes even in biological systems. NO and HS are such molecules that are nowadays recognized as biological gasotransmitters involved in the regulation of physiological functions through protein modifications such as S-nitrosothiol, disulfide, and persulfide formations. In this Viewpoint, we review the current understanding of interactions of NO (and organic and metal nitrosyl species) with HS, in both chemical and biochemical contexts. Through the formation of HNO, (H)SNO (and its isomers), (H)SSNO, and polysulfides, these two gasotransmitters initiate reaction networks with significant roles in cell signaling. The chemical reactivities and biological effects of these nitrogen and sulfur species are still unresolved, and, thus, a cross-talk between all of them represents a challenging interdisciplinary field that awaits exciting new findings. We tackle some of the intriguing and open questions and provide perspectives for future research directions.