Ruthenium(II) complex-based long-lived two-photon luminescence probe for dynamic monitoring of glutathione S-transferases in mouse models of drug-induced liver injury

We report a novel ruthenium(II) complex-based long-lived and two-photon luminescence probe, Ru-NO2, for dynamic monitoring of GSTs fluxes in the process of drug-induced liver injury (DILI). Ru-NO2 shows weak luminescence due to the strong photo-induced electron transfer (PET) process from the Ru(II) center to the electron-withdrawing 3,4-dinitrobenzene (DNB) group. As a result of the specific nucleophilic aromatic substitution triggered by GSTs in the presence of reduced glutathione (GSH), the 4-nitro group of Ru-NO2 is substituted by GSH to form strongly emissive Ru-SG. Ru-NO2 shows high selectivity and sensitivity for responding to GSTs. Notably, one- and two-photon luminescence imaging experiments were conducted to visualize GSTs in living cells and mouse tissues. In addition, Ru-NO2 was applied for background-free time-gated luminescence (TGL) detection and luminescence imaging analysis of GSTs in DILI mouse sera and liver tissues, which showed that GSTs level in sera significantly increased accompanied by the decrease in liver in the DILI process, revealing the possible potential of the probe as an effective tool for clinical diagnosis and treatment monitoring of DILI.