Dual-Fluorophore and Dual-Site Multifunctional Fluorescence Sensor for Visualizing the Metabolic Process of GHS to SO 2 and the SO 2 Toxicological Mechanism by Two-Photon Imaging.

As a momentous gas signal molecule, sulfur dioxide (SO 2 ) participates in diverse physiological activities. Excess SO 2 will cause an apparent decrease in the level of intracellular glutathione (GSH), thereby damaging the body's antioxidant defense system. In addition, endogenous SO 2 can be generated from GSH by reacting with thiosulfate (S 2 O 3 2- ) and enzymatically reduced to cysteine (Cys), a synthetic precursor of GSH. In view of their close correlation, a two-photon (TP) mitochondria-targeted multifunctional fluorescence sensor Mito-Na-BP was rationally designed and synthesized for detecting SO 2 and GSH simultaneously. Under single-wavelength excitation, the sensor responded to GSH-SO 2 and SO 2 -GSH continuously with blue-shifted and green fluorescence-enhanced signal modes, respectively, not just to GSH (enhanced) and SO 2 (quenched) at 638 nm with a completely converse response tendency. Given its favorable spectral performance (high sensitivity, superior selectivity, and fast response rate) at physiological pH, Mito-Na-BP has been successfully applied in monitoring the level fluctuation of GSH affected from high-dose SO 2 and visualizing in real time the metabolic process of GSH to SO 2 by TP imaging. It is expected that this research will provide a convenient and efficient tool for elucidating intricate relationships of GSH and SO 2 and facilitate further exploration of their functions in biomedicine.