Exploring Meso-Six-Membered-N-Heterocycle BODIPY Rotors as AIE Probes for Fluorescence Imaging Subcellular Viscosity in Organelles

Aggregation-induced emission (AIE)-type small-molecular fluorescent rotors have attracted wide interest due to their inherent excellent properties in bioimaging viscosity, which can potentially reveal the relationships between microviscosity and related diseases. Although many fluorescent probes have been designed, easy-to-prepare and multifunctional AIE rotors remain a hot topic and less reported. Herein, four easy-to-prepare and water-soluble meso-pyrimidine/pyridine BODIPY-based multifunctional fluorescent probes were rationally designed to investigate the effects of the number and position of nitrogen in six-membered-N-heterocycles on viscosity, AIE, and viscosity imaging. Luckily, the meso-o-pyrimidine-based probe 1 displayed significant fluorescence enhancements at 525 nm with gradually increasing viscosity from water to glycerol, which also showed obvious AIE property in an acetonitrile/water mixture due to two nitrogen at the ortho positions of pyrimidine. Meso-o-pyridine-based 2 exhibited no viscosity-enhanced emissions, but obvious AIE enhancements appeared. Comparatively, the meso-m-pyridine-based probe 3 showed no viscosity- and aggregation-induced emission enhancements, while the meso-p-pyridine-based one 4 displayed obvious viscosity response without AIE character. Furthermore, 1 and 4 were applied to cellular imaging, which displayed lysosomal and mitochondrial localizations in HeLa cells, respectively, and successfully monitored viscosity variations induced by the addition of lipopolysaccharide (LPS) or monensin. In summary, four meso-pyrimidine and meso-pyridine-BODIPY multifunctional fluorescent rotors have been prepared using easy synthesis, in which meso-o-pyrimidine and meso-o-pyridine ones showed improved AIE properties in water, and meso-o-pyrimidine and meso-p-pyridine ones showed good subcellular localization and viscosity changes in HeLa cells. This work can provide an easy-to-prepare and useful strategy for multifunctional fluorescent probes with enhanced AIE property for imaging viscosity and other applications.