Activity-Based Fluorescent Probes for Reactive Sulfur Species
Ming Xian, Yuqing Wang, Chunfang Du, Meg Shieh
Abstract
Conspectus Reactive sulfur species (RSS), such as hydrogen sulfide (H 2 S), hydrogen per/polysulfide (H 2 S n, n > 1), hydropersulfides (RSSH), and polysulfides (RS n R, 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 H 2 S that could distinguish H 2 S from other RSS. Based on the reactions, we developed several series of H 2 S probes. We then investigated the reactions of other RSS, including H 2 S 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 H 2 S 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.