Activity-Based Fluorescent Probes for Reactive Sulfur Species

Reactive sulfur species (RSS), such as hydrogen sulfide (H₂S), hydrogen per/polysulfide (H₂S_n, n > 1), hydropersulfides (RSSH), and polysulfides (RS_nR, n > 2), are believed to play regulatory roles in redox biology. However, their exact mechanisms of action still need to be clarified. The instability of various RSS under physiological environments and their highly reactive natures pose unique challenges to the research on these species. Considering these challenges, fluorescent probes that can rapidly and specifically detect each individual RSS in biological settings are critical tools for RSS research. This Account follows our laboratory’s development of such probes.

We began by exploring the specific reactions of H₂S that could distinguish H₂S from other RSS. Based on the reactions, we developed several series of H₂S probes. We then investigated the reactions of other RSS, including H₂S_n, sulfane sulfur, HSNO, etc., and developed the corresponding probes. Our research on these probes also inspired us to develop other related chemical tools, including H₂S scavengers and a general structural template for xanthene-based near-infrared dyes. This Account summarizes our work in this field and systematically explains how each probe/chemical tool was designed and evaluated. This Account covers the following key points: (1) the rational chemical design of each probe template; (2) the evaluation and mechanistic insights for each probe template; and (3) the properties and applications of the probes/chemical tools.