A multiple acetal chalcone-BODIPY-based fluorescence: synthesis, physical property, and biological studies.

ABSTRACT

Fluorescent probes with outstanding physical and biological properties are superior for functional fluorescent dyes design. However, few studies pay attention to the stability of specific groups in fluorescent probes. The aldehyde group in the fluorescent probe is highly active but unstable under certain conditions. Therefore, we introduced ethoxy groups to realize the conversion to aldehyde groups under acidic conditions and avoid the instability of straightforward aldehyde groups. In this work, two fluorophores based on the multi acetal difluoroboraindacene (BODIPY) units with combination of the pharmaceutical intermediate chalcone have been firstly developed. In the design part, chalcone was introduced as a medium for fluorophore and multiple acetal. The mild synthesis strategy is based on the ligand ((Z)-2-chloro-1-(difluoroboranyl)-5-((4-ethyl-3,5-dimethyl-2H-pyrrol-2-ylidene)(phenyl)methyl)-1H-pyrrole) and connects with chalcone in (2E,2'E)-3,3'-(1,3-phenylene)bis(1-(2,4-bis(2,2-diethoxyethoxy)phenyl)prop-2-en-1-one). The emission wavelengths of the products are around 530 nm with high fluorescence intensity. To highlight the biological characteristics of these novel BODIPY fluorescents, we further demonstrated biological analysis studies on MTT and flow cytometry assays. The IC50 values of BODIPY 5 ranged from 79 ± 6.11 to 63 ± 5.67 µM and BODIPY 6 were found to be 86 ± 4.07 to 58 ± 10.51 µM in tested cell lines. Flow cytometry data analysis shows that the representative agent 6 and reference have similar rational apoptosis rates in first quadrant. Last but not least, 6 shows outstanding biological compatibility and cell imaging potential in live cell imaging and in vivo assay, not only is the fluorescence prominent enough, but also rapidly distributes. Thus, our study reports a mild synthesis strategy and full biological analysis on BODIPY fluorescents, and the subtle modulation of the physical and biological properties by pharmaceutical substituents makes these designed chalcone-BODIPY-based dyes hopeful to realize drug functional fluorescent dyes. Two new highly sensitive BODIPY fluorophores are synthesized based on the ligand ((Z)-2-chloro-1-(difluoroboranyl)-5-((4-ethyl-3,5-dimethyl-2H-pyrrol-2-ylidene)(phenyl)methyl)-1H-pyrrole), which connects with chalcone in (2E,2'E)-3,3'-(1,3/4-phenylene)bis(1-(2,4-bis(2,2-diethoxyethoxy)phenyl)prop-2-en-1-one). Multiple acetals were introduced and the physical and biological properties of BODIPYs are described with MTT assay and in vitro and in vivo imaging.