BODIPY-based Fluorescent Probes For Biological Recognition And Environment Sensing In Cells

Difluoroboron dipyrromethene (BODIPY) dyes show high application potential in many fields because of their many excellent photophysical properties, such as robustness against light and chemicals, high molar absorption coefficients and fluorescence qutantum yields, narrow emission bandwidths with high peak intensities, and so forth. This thesis focuses on the design, synthesis, properties evaluation, and live-cell imaging applications of BODIPY-based fluorescent probes for biologcial recognition and environment sensing.To investigate lysosomal zinc functions in neurons, a lysosome-targeted zinc probe LysoZn-1 was developed. It is derived from the styryl-BODIPY-di(2-picolyl)amine (DPA) scaffold with a 2-morpholinoethylamine moiety. LysoZn-1 exhibits high selectivity to Zn2+ over other ions (including Cd2+) and pH. LysoZn-1 is able to localize to lysosomes in live cells and detect exogenous and endogenous Zn2+levels in neural stem cells (NSCs).Reactive oxygen species (ROS) have long been associated with cancers. Unfortunately, the role of HOCl in tumor biology is still unclear. BClO is a HOCl-selective fluorescent probe with ultrasensitivity (detection limit is 0.56 nM, the highest sensitivity achieved to date) and fast response (completed within 1 s), in which meso-pyrrole group has an "enhanced photoinduced electron transfer (PET)" effect on BODIPY fluorophore. BCIO can be facilely synthesized by a Michael addition reaction of acryloyl chloride with 2,4-dimethylpyrrole, and applied to image the basal and elescolmol-induced HOCl in cancer cells.Viscosity is a critical factor governing the diffusion-mediated cellular processes. BV-1 is a "distorted-BODIPY"-based viscosity probe, which is different from the conventional "pure rotors". In BV-1, the internal steric hindrance forces the boron-dipyrrin framework to be distorted, which mainly causes nonradiative deactivation in low-viscosity environment. BV-1 gives high sensitivity together with stringent selectivity to viscosity, enabling its application in monitoring the increase of cytoplasmic viscosity during apoptosis.Polarity is a significant environment-related factor that reflects the activities of a variety of biological processes. A series of d-PET-based "off-on" fluorescent probes (BP-1, BP-2, BP-3, and BP-4) for polarity were developed, among which BP-2 gives good linear response, high sensitivity and specificity to polarity. BP-2 can be synthesized by an unusual Mannich reaction of meso-methyl BODIPY with dimethylamine in dichloromethane and subsequent methylation. BP-2 has been proved to specifically localize to lysosomes and be capable of reporting the fluctuations of cellular polarity stimulated by sucrose and chloroquine in live cells.