苯并噻二唑类化合物的高效合成与脂滴的荧光成像应用OA

Owing to their outstanding photophysical properties,robust chemical stability,and facile structural modifications,benzothiadiazole derivatives have important applications in the fields of fluorescent probes,biological imaging,and related interdisciplinary research.However,the currently reported synthetic routes for these functional compounds are plagued by prominent limitations,such as the reliance on costly phosphine ligands,use of toxic volatile organic solvents,and harsh reaction conditions,including prolonged reaction duration and elevated temperatures,which greatly restrict their large-scale preparation and practical application.To overcome these limitations,we developed a highly efficient ligand-free and eco-friendly Suzuki coupling reaction.This system used palladium acetate as the catalyst,potassium carbonate as the base,and an ethanol-water solution as the green reaction medium to realize efficient coupling between 4,7-dibromo-2,1,3-benzothiadiazole and arylboronic acids bearing diverse substituents.Using this optimized protocol,12 benzothiadiazole compounds were synthesized in isolated product yields of up to 97%.Photophysical property tests demonstrated that nearly all 12 target compounds were polarity-responsive molecules whose emission wavelengths exhibited a significant redshift with increasing solvent polarity.Among them,BTD-6 displayed optimal polarity-responsive performance,and its fluorescence characteristics remain highly stable in complex biological environments without interference from microenvironmental factors,such as pH,viscosity,or temperature.MTT assays confirmed that BTD-6 possesses favorable biocompatibility without obvious cytotoxicity.Laser confocal microscopy imaging demonstrated that BTD-6 has a specific lipid droplet-targeting capability in both HeLa and HT-1080 cells,enabling real-time detection of dynamic changes in intracellular lipid droplet content,thus serving as a high-performance fluorescent probe for lipid droplet-related biological imaging.This study provides a novel green synthetic strategy for benzothiadiazole-based compounds,and the developed BTD-6 probe shows excellent performance in lipid droplet-targeted imaging and dynamic monitoring,laying an important foundation for the diagnosis of related diseases and mechanistic research.