Design, synthesis and evaluation of a novel hepatocyte-targeting fluorescent probe to accurately detect H2S in mitochondria

A novel hepatocyte-targeting and mitochondria-targeting fluorescent probe Dye-H2S-Gal was designed and synthesized. Dye-H2S-Gal with low toxicity and short response time (within 1 min) shows good selectivity toward H2S, which is not disturbed by anions (CO32−, SO42−, HCO32−, T-BuO-), reactive oxygen and biothiols (Cys, GSH, H2O2, T-BuO-) and the representative cations (Ag+, Ba2+, Ca2+, Cd2+, Ce2+, Co2+, Cr2+, Cu2+, Eu3+, Fe2+, Fe3+, Hg2+, K+, Li+, Mg2+, Mn2+, Ni2+, NH4+, Na+). The OFF-ON switch of Dye-H2S-Gal is triggered by H2S via removing the thiophenecarboxylate group. Good mitochondria-targeting capacity of Dye-H2S-Gal is driven by the electrostatic interaction between a quaternary amine group of Dye-H2S-Gal with positive charge and the mitochondria membrane with negative charges, and its good hepatocyte-targeting capacity is driven by the specific recognition of the galactose group on the asialoglycoprotein receptor (ASGPR) overexpressed on liver cells. On the whole, Dye-H2S-Gal can precisely monitor mitochondria H2S level in liver cells and is of great significance for the early diagnosis and precise treatment of liver diseases.