Novel meso-trifluoromethyl BODIPY-based near-infrared-emitting fluorescent probes for organelle-specific imaging of cellular viscosity

Abstract

Fluorescent molecular rotors play vital roles in understanding the function of cellular viscosity changes and its abnormal fluctuations are closely associated with many diseases. Despite numerous efforts spent, it remains an urgent and important topic to develop improved viscosity probes with near-infrared fluorescence, high sensitivity and low background. In this manuscript, for the first time, we reported two novel monostyryl boron dipyrromethenes (BODIPYs) bearing a rotatable trifluoromethyl group (CF3) at the meso position and a triphenylphosphonium (4) or morpholine (6) substituent, which could successfully serve as highly sensitive and near-infrared-emitting fluorescent probes for imaging cellular viscosity in mitochondria or lysosome. These probes could be prepared through Knoevenagel condensation under mild conditions and showed negligible emissions in the low viscous solvents. However in high viscous glycerol, strong near-infrared fluorescence at 657 nm appeared, ascribed to the substantially restricted rotation of the CF3 group. Their fluorescence intensity (log I) at 657 nm exhibited a good linear relationship with viscosity (log η) in the whole test range of 1–950 cP. Limit of detection for viscosity of mitochondria-targeting probe 4 was relatively lower than that of lysosome-targeting probe 6. These probes both showed no cytotoxicity and good mitochondrial or lysosomal localization. Interestingly, mitochondria-targeting probe 4 exhibited a remarkable intracellular fluorescence enhancement with viscosity increase induced by LPS or nystatin, which was better than lysosome-targeting probe 6. These two novel BODIPY-based fluorescent rotors provide a new strategy for developing near-infrared-emitting and organelle-specific fluorescent probes for cellular viscosity, which might be useful in exploring the functions of viscosity in various diseases.