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 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.

Progress and perspective on hydrogen sulfide donors and their biomedical applications

“…On this ground, H 2 S‐releasing agents (also named H 2 S donors) seem to be adequate for either mimicking the endogenous H 2 S generation under physiological conditions, or replenishing additional H 2 S for both diagnostic and therapeutical purposes. During the past years, substantial endeavor has been made to develop various H 2 S donors, and a number of H 2 S donors with different releasing rates and mechanisms have been reported 101,105–125 . H 2 S donors, regarded as the exogenous suppliers of H 2 S, could be employed as the ideal candidates for the treatment of diseases whose H 2 S‐associated networks might be short‐circuited.…”

Intelligent polymeric hydrogen sulfide delivery systems for therapeutic applications

“…When photoactivated groups such as o -nitrobenzyl [ 106 ] or boron dipyrromethene chromophores with different substituents [ 107 , 108 ] were linked, UV to NIR light activated H 2 S release could be achieved. In addition, through the linkage of appropriate fluorophores, self-reporting release of COS could also be achieved for real-time monitoring [ [109] , [110] , [111] , [112] ]. Furthermore, an oligo(thiourethane) containing S -alkyl thiocarbamate linkers was synthesized through the polyaddition of 4-isothiocyanatobenzyl alcohol and end-capped with aryl azide, which could undergo self-amplified depolymerization to release multiple equivalents COS in response to per equivalent of H 2 S [ 113 ].…”

Thioredoxin reductase-triggered fluorogenic donor of hydrogen sulfide: a model study with a symmetrical organopolysulfide probe with turn-on near-infrared fluorescent emission

“…In 2021, Zhang and co-workers reported the cysteine-induced release of H 2 S with turn-on fluorescence from a phenyl thiocarbamate-based probe ( Pro-S ) in aqueous and cellular media with further validation in a zebrafish model. 23 This was the first report of fluorogenic H 2 S donation with emission in the near-infrared (NIR) region. However, the major limitation of the probe was its only responsiveness towards cysteine, a non-abundant cellular biothiol (GSH is the highly abundant intracellular biothiol).…”