Methyl-free meso-thiazole-substituted red-shifted BODIPY-based molecular rotor for fluorescence imaging viscosity in mitochondria

Abstract

Molecular fluorescent rotors based on boron dipyrromethenes (BODIPYs) were intensively explored for monitoring the environmental viscosity variations, due to its critical functions in many associated diseases. Although various strategies have been used, red-shifted BODIPY-based fluorescent rotors with large Stokes shifts through one-step reaction remain a challenging topic due to the tedious synthetic procedures. In this manuscript, for the first time, through one-step reaction, 1,7-dimethyl-free meso-thiazole/benzothiazole BODIPYs were used to construct red-shifted fluorescent rotors with large Stokes shifts, which could be used for monitoring cellular viscosity changes with mitochondrial localization. This strategy-designed 1,7-dimethyl-free meso-thiazole/benzothiazole BODIPYs could be prepared through one-step reaction, giving emissions over 600 nm and large Stokes shifts of about 70 nm. Both meso-thiazole probe 3 and meso-benzothiazole probe 5 could sense the viscosity changes through fluorescence turn-on effects with low detection limits, depending on efficiently restricting the rotation of the meso-thiazole in viscous systems. Cellular experiments further validated that probe 3 showed nearly no cytotoxicity towards HeLa cell and relatively good mitochondria-targeting ability over lysosomes, which was further employed to detect intracellular viscosity variations induced by lipopolysaccharide (LPS) and monensin. Therefore, red-shifted 1,7-dimethyl-free meso-thiazole BODPY-based fluorescent probe through one-step reaction could serve as sensitive molecular rotors for visualizing viscosity variations in mitochondria of HeLa cells.