An Activatable Near-Infrared Fluorescence Hydrogen Sulfide (H2S) Donor for Imaging H2S Release and Inhibiting Inflammation in Cells

Hydrogen sulfide (H2S) is a vital endogenous signal molecule that exerts critical physiological functions such as biological regulation and cytoprotection. Despite significant progress in developing H2S donors, site-specific delivery and controllable release of H2S in biological systems remain a key challenge. Herein, we develop new Cys-triggered fluorescent H2S donor Pro-S that is composed of a dicyanoisophorone-based near-infrared (NIR) fluorescent dye and a thiocarbamate moiety. The H2S donor releases H2S under the attack of Cys, accompanied by the release of a fluorescent reporter, which enables the real-time capturing of H2S by fluorescence spectroscopy or microscopy. Pro-S exhibits strong NIR fluorescence enhancement (70-fold), excellent controllable H2S release (30 min), high H2S release efficiency (62%), and well live-cell compatibility, allowing for visualization of H2S 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 H2S donors, which may be beneficial to the comprehension of the potential mechanism of inflammation and optimization of treatment strategies.

Automated summary

Hydrogen sulfide (H2S) is a vital endogenous signal molecule with critical physiological functions, but its site-specific delivery and release in biological systems remains a challenge. The newly developed Pro-S donor shows excellent release efficiency and live-cell compatibility, allowing real-time capturing of H2S and demonstrating anti-inflammatory effects in cells.