An Activatable Near-Infrared Fluorescence Hydrogen Sulfide (H 2 S) Donor for Imaging H 2 S Release and Inhibiting Inflammation in Cells.

Hydrogen sulfide (H ₂ S) is a vital endogenous signal molecule that exerts critical physiological functions such as biological regulation and cytoprotection. Despite significant progress in developing H ₂ S donors, site-specific delivery and controllable release of H ₂ S in biological systems remain a key challenge. Herein, we develop new Cys-triggered fluorescent H ₂ S donor Pro-S that is composed of a dicyanoisophorone-based near-infrared (NIR) fluorescent dye and a thiocarbamate moiety. The H ₂ S donor releases H ₂ S under the attack of Cys, accompanied by the release of a fluorescent reporter, which enables the real-time capturing of H ₂ S by fluorescence spectroscopy or microscopy. Pro-S exhibits strong NIR fluorescence enhancement (70-fold), excellent controllable H ₂ S release (30 min), high H ₂ S release efficiency (62%), and well live-cell compatibility, allowing for visualization of H ₂ S release in cells and zebrafish. Moreover, Pro-S presents a good effect of anti-inflammation in RAW 264.7 cells. This work provides a new idea for the design of H ₂ S donors, which may be beneficial to the comprehension of the potential mechanism of inflammation and optimization of treatment strategies.