Near-infrared fluorescent probes based on tetrahydroacridine moiety with large Stokes shifts for monitoring mitochondrial viscosity during autophagy

Motivated by the demand for near-infrared fluorescent probes in monitoring variations in the intracellular microenvironment, three semi-cyanine near-infrared fluorescent probes with viscosity sensitivity were designed based on the D-π-A structure in this paper. The probes 1a-c consisted of a 1, 2, 3, 4-tetrahydroacridine moiety and an electron-donating group coumarin unit or N,N-diethylphenyl, linked by carbon–carbon double bonds. Optical experiments revealed NIR emission wavelengths (663–809 nm) with large Stokes shifts (132–275 nm) in different solvents, which would reduce the interference of background fluorescence in biological imaging. Moreover, they presented viscosity dependence in the range of 0.89–856 cP, exhibiting nearly OFF-ON fluorescence responses. In addition, the probes had mitochondrial targeting properties and it was verified that the probes could monitor the fluctuations of mitochondrial viscosity during autophagy in HeLa cells in real time by modeling starvation and drug induction (nystatin, rapamycin). Therefore, the outstanding features of probes 1a-c might provide potential implications for the early diagnosis of various diseases induced by changes in abnormal mitochondrial viscosity.