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We report here that a fluorescent benzobisimidazolium salt (TBBI) can be used for the fluorescent and colorimetric detection of carbonyl sulfide (COS) over related heterocumulenes including CO 2 and CS 2 in wet MeCN. The reaction between TBBI and COS in the presence of fluoride yields a highly fluorescent ( λ em = 354 nm) and colored product ( λ max = 321, 621 nm), that is readily observed by the naked eye. We view these results as a first step toward developing activity-based probes for COS detection. 

Hydrogen sulfide (H 2 S) is an important cellular signaling molecule that exhibits promising protective effects. Although a number of triggerable H 2 S donors have been developed, spatiotemporal feedback from H 2 S release in biological systems remains a key challenge in H 2 S donor development. Herein we report the synthesis, evaluation, and application of caged sulfenyl thiocarbonates as new fluorescent H 2 S donors. These molecules rely on thiol cleavage of sulfenyl thiocarbonates to release carbonyl sulfide (COS), which is quickly converted to H 2 S by carbonic anhydrase (CA). This approach is a new strategy in H 2 S release and does not release electrophilic byproducts common from COS-based H 2 S releasing motifs. Importantly, the release of COS/H 2 S is accompanied by the release of a fluorescent reporter, which enables the real-time tracking of H 2 S by fluorescence spectroscopy or microscopy. Dependent on the choice of fluorophore, either one or two equivalents of H 2 S can be released, thus allowing for the dynamic range of the fluorescent donors to be tuned. We demonstrate that the fluorescence response correlates directly with quantified H 2 S release and also demonstrate the live-cell compatibility of these donors. Furthermore, these fluorescent donors exhibit anti-inflammatory effects in RAW 264.7 cells, indicating their potential application as new H 2 S-releasing therapeutics. Taken together, sulfenyl thiocarbonates provide a new platform for H 2 S donation and readily enable fluorescent tracking of H 2 S delivery in complex environments. 

Dithioesters have a rich history in polymer chemistry for RAFT polymerizations and are readily accessible through different synthetic methods. Here we demonstrate that the dithioester functional group is a tunable motif that releases H 2 S upon reaction with cysteine and that structural and electronic modifications enable the rate of cysteine-mediated H 2 S release to be modified. In addition, we use (bis)phenyl dithioester to carry out kinetic and mechanistic investigations, which demonstrate that the initial attack by cysteine is the rate-limiting step of the reaction. These insights are further supported by complementary DFT calculations. We anticipate that the results from these investigations will allow for the further development of dithioesters as important chemical motifs for studying H 2 S chemical biology.