Novel Meso-Benzothiazole-Substituted BODIPY-Based AIE Fluorescent Rotor for Imaging Lysosomal Viscosity and Monitoring Autophagy.

ABSTRACT

Meso-substituted boron dipyrromethenes (BODIPYs) provide a potential and innovative strategy for the synergistic construction of aggregation-induced emission (AIE) probes and fluorescent rotors for monitoring cellular viscosity changes, which play critical roles in understanding the function of viscosity in its closely associated diseases. Therefore, for the first time, a BODIPY-based fluorescent probe (1) with a rotatable meso-benzothiazole group was rationally designed and synthesized, showing both good viscosity-responsive and AIE properties. Probe 1 through direct linkage with the thiazole group, showed nearly no emission in low viscous solvents; however, a strong emission at 534 nm appeared and increased gradually with the increase in viscosity, attributing to the efficient restriction of the rotatable meso-benzothiazole group. The intensity (log I534) displayed a good linear relationship with viscosity (log η) in the viscous range of 0.59-945 cP in methanol/glycerol mixtures. Interestingly, 1 showed enhanced emission at 534 nm in 70% water compared to pure acetonitrile due to the aggregation-induced inhibited rotations. Cellular imaging suggested that 1 could successfully sense lysosomal viscosity changes induced by lipopolysaccharide, nystatin, low temperature, and dexamethasone in living cells, which could be further applied in autophagy monitoring by tracing viscosity changes. As a comparison, its analogue 2 directly linking with the phenyl group showed no viscosity-responsive or AIE properties. Therefore, for the first time, we reported a meso-benzothiazole-BODIPY-based fluorescent rotor with AIE and lysosomal viscosity-responsive properties in nervous cells, which was further applied in monitoring autophagy, and this work thus could provide an innovative strategy for the design of potential AIE and viscosity-responsive probes.