A near-infrared fluorescent probe selectively recognizing cysteine to release H2S and its applications†

Cysteine, a pivotal biothiol vital for human health, exhibits strong associations with various diseases, yet its concentration assessment is often confounded by structurally and functionally similar biothiols. Hydrogen sulfide (H₂S), an endogenous gasotransmitter with therapeutic potential, faces challenges in achieving pharmacological effects due to the unpredictable presence of inorganic H₂S donors. To address these issues, we developed TMN-ONCS, a near-infrared fluorescent probe that integrates a p-tolyl isothiocyanate with a dicyanoisophorone fluorophore through a self-immolative spacer. TMN-ONCS demonstrates high selectivity and analytical performance for cysteine, avoids the generation of multiple fluorophores seen in conventional isothiocyanate probes, and functions as a cysteine-activated fluorescent H₂S donor with concurrent visualization. Furthermore, it mitigates lipopolysaccharide-induced inflammation in RAW 264.7 cells, highlighting its potential for treating inflammation.