Synthesis, molecular docking calculation, fluorescence and bioimaging of mitochondria-targeted ratiometric fluorescent probes for sensing hypochlorite in vivo.

Abstract

Mitochondria are the main sites for the production of hypochlorite (OCl-). The protein adenine nucleotide translocase (ANT) is located in the inner mitochondria membrane, which is mainly participated in the transportation of ions and metabolites. At the cellular organelle level, overexpression of ANT is associated with enhanced production of OCl-, however, abnormal levels of OCl- cause redox imbalance and loss of function of mitochondria. Herein, a novel mitochondria-targeted ratiometric fluorescent probe Mi-OCl-RP has been developed. Molecular docking calculation suggested a potential molecular target for the probe in the ANT, and the high binding energy (-8.58 kcal mol-1) may explain the high mitochondria selectivity of Mi-OCl-RP. The unique probe exhibits excellent spectral properties including ratiometric fluorescence response signals to OCl- (within 7 s), high selectivity and sensitivity, and a large Stokes shift (278 nm). In addition, the colocalization coefficient confirms that Mi-OCl-RP can effectively target mitochondria. Furthermore, Mi-OCl-RP has low toxicity and good permeability, and was successfully employed in ratiometric imaging of OCl- in vivo, affording a robust molecular tool for investigating the biological functions of OCl- in living systems.