Prodrugs of Persulfides, SO₂, and CS₂: Important Tools for Studying Sulfur Signaling at Various Oxidation States.

Bioactive sulfur species such as hydrogen sulfide (H₂S), persulfide species (R-S_nSH, n≥1), hydrogen polysulfide (H₂S_n, n≥2), sulfur dioxide (SO₂) and carbon disulfide (CS₂) participate in various physiological and/or pathological pathways such as vasodilation, apoptosis, inflammation and energy metabolism regulation. The oxidation state of the individual sulfur species endows them unique biological activities. Recent Advances: There have been great strides made in achieving molecular understanding of the sulfur-signaling processes.The development of various chemical tools that deliver reactive sulfur species in a controllable manner has played an important role in understanding the different roles of various sulfur species. In this review, we focus on three types of sulfur species including persulfide, sulfur dioxide (SO₂) and carbon disulfide (CS₂). Starting with a brief introduction of their physiological functions, we will then assess the various drug delivery strategies to generate persulfide species, SO₂ and CS₂ as research tools and potentially as therapeutic agents.Development of donors of various sulfur species that respond to distinct stimulus is critical for this field. Another key to the long-term success of this field is the identification an area of unmet medical need that can be addressed with these sulfur species.