A multi-signal mitochondria-targetable fluorescent probe for simultaneously discriminating Cys/Hcy/H_2S, GSH, and SO_2 and visualizing the endogenous generation of SO_2 in living cells

摘要

Reactive sulfur species (RSS) include sulfur dioxide (SO_2) and various biothiols, such as hydrogen sulfide (H_2S), glutathione (GSH), cysteine (Cys), and homocysteine (Hcy). These RSS are closely related to each other through complicated symbiotic networks, and play indispensable roles in multiple pathophysiological processes. Due to their similarity in chemical properties, it is challenging for developing a single fluorescent probe to differentiate them simultaneously. Herein we report the first mitochondria-targetable fluorescent probe NIR-NBD for simultaneous discrimination of Cys/Hcy/H_2S, GSH, and SO_2 from each other. The probe is characterized of the presence of three different types of electrophilic sites, and displays multiple sets of signal pattern in response to Cys/Hcy/ H_2S, GSH, and SO_2, including red-green for Cys/Hcy/H_2S, red for GSH, and green for SO_2. Notably, the probe exhibits excellent selectivity, outstanding sensitivity (detection limit = 3.5 nM) and fast response (within 4 min) toward SO_2. Furthermore, the probe has been successfully applied for monitoring mitochondrial SO_2 and various biothiols, visualizing the endogenous generation of SO_2, and probing into the role of biothiols during apoptosis process.