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

Abstract

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 <b>Pro-S</b> 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. <b>Pro-S</b> 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, <b>Pro-S</b> 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.