Gold(i) N-heterocyclic carbene complexes with tunable electronic properties for sensitive colorimetric detection of glutathione

Abnormal glutathione (GSH) is associated with various diseases, like Parkinson's disease, cancer, and cardiovascular disease. The efficient detection of GSH has been a research focus for many years. However, using the current methods it remains a grand challenge to substantially enhance the detection sensitivity and selectivity of GSH, owing to the unavoidable influence of other molecules containing free sulfhydryl groups when detecting GSH. Herein, a series of sterically and electronically modulated Au(i)-N-heterocyclic carbene (NHC) complexes were synthesized and applied for GSH detection. We demonstrated that the Au(i)-NHC complexes exhibited peroxidase-like activity, and could catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) in the presence of H₂O₂ to produce blue oxidized TMB. Significantly, the catalytic activity could be enhanced by introducing electron-withdrawing moieties on the NHC backbone. As a proof-of-concept application, an Au(i)-NHC complex catalyzed TMB + H₂O₂ system is designed as a reliable colorimetric assay for sensitive detection of GSH, which displays a low detection limit of 0.14 μM. The present findings provide an efficient strategy to discriminate GSH, which can remarkably extend the potential applications of Au(i)-NHC complexes as novel colorimetric biosensors and also open promising avenues for more powerful biosensors that operate upon other metal-NHC complexes.