A mitochondria-targeted iridium(III) complex-based sensor for endogenous GSH detection in living cells

Glutathione (GSH) plays an important role in maintaining redox homeostasis in biological systems. Development of reliable glutathione sensors is of great significance to better understand the role of biomolecules in living cells and organisms. Based on the advantages of the photophysical properties of iridium complexes, we proposed a "turn-on" phosphorescent sensor. Ir-DNFB has the characteristics of a large Stokes shift, high sensitivity for GSH detection, low cytotoxicity, and extremely short response time, and can specifically analyze glutathione in living cells and highly target endogenous glutathione in mitochondria. The N-H group on the imidazole ring of Ir-DNFB could form a new electrostatic interaction with the α-carboxyl group on the glutamate moiety of glutathione. The nucleophilic attack reaction was regulated by the sulfhydryl group on GSH, following which the ether bond linking the 2,4-dinitrobenzene to probe Ir-DNFB was broken, accompanied with a phosphorescence enhancement. Most importantly, the process of recognizing glutathione was not affected by other amino acids. Overall, this work provided a very useful tool for rapidly distinguishing between normal, inflammatory, and progressive tumor cells.