Study On The Synthesis And Biological Activity Of Boron Dipyrromethene(BODIPY)Derivative And Nanoassembly

BODIPY?4,4-difluoro-4-bora-3a,4a-diaza-s-indacene?fluorescent dyes exhibited excellent properties such as easy modification,high fluorescence quantum yield,high molar absorption coefficient.Functionalized BODIPY dyes have broad application prospects in the fields of bioimaging,fluorescent probes,targeted drug design,and antimicrobial applications.The study of BODIPY fluorescent dyes and their water-soluble nanoassemblies plays an important role in the development of environmental detection probes and biomedical nanomaterials.Therefore,exploring the interaction of BODIPY derivatives with G-quadruplex and protein has far-reaching significance for the development of a new BODIPY fluorescent nano-assembly with good biocompatibility and excellent performance.BODIPY compounds and their research progress in photodynamic antitumor,antibacterial,metal ion detection and BODIPY nanoassemblies were systematically summarized in this thesis.Four new BODIPY compounds and four nanoassemblies were designed and synthesized.The structures of the compounds and complexes were characterized by NMR,ESI-MS,IR,UV-vis,fluorescence spectroscopy and TEM.In addition,the inhibitory effect of nanoassemblies on tumor cells,the recognition of metal ions,the detection of Escherichia coli?E.coli?and the antibacterial application were studied.The main innovative results are as follows:?1?Two new compounds,BTPA1 and BTPA2,were synthesized by coupling triphenylamine?TPA?with BODIPY.Their recognition with G-quadruplex were explored by means of spectral analysis and theoretical calculation.It was found that BTPA2 can recognize G-quadruple aptamer?G3T3?and combined with G3T3 to form a water-soluble nanohydrogel?BTPA2-G3T3?.In addition,the experimental results indicate that BTPA2-G3T3 can enter mitochondria,reduce membrane potential of mitochondria,inhibit the expression of TrxR2 protein in mitochondria and its fluorescence emission changes with the number of tumor cells,which can be used as a fluorescent probe for tumor cell response.Therefore,the multi-effect BTPA2-G3T3 is a multifunctional nano-fluorescent hydrogel that integrates a mitochondrial imaging agent with a membrane potential modulator and a TrxR2 protein inhibitor.The preparation of such hydrophobic fluorescent compounds and G-quadruplex recognition and assembly to form nano-fluorescent hydrogels provides a new method for converting hydrophobic compounds into hydrogels with better biocompatibility.This was first reported internationally.?2?A new antibacterial dye was synthesized by coupling natural antibacterial agent phenethyl caffeate?CAPE?with brominated BODIPY.It was encapsulated in the metal organic framework ZIF-90 together with the pH-jump reagent2-nitrobenzaldehyde?o-NBA?toformphotoactivatednanoparticles BC&o-NBA@ZIF-90.Experiments show that under the illumination of blue LED light,the photolabile substance o-NBA will rapidly increase the proton concentration in the solution,making the surrounding environment acidic.The ZIF-90 structure decomposes under acidic conditions to achieve release of the antimicrobial agent?BC?.The antibacterial agent releases singlet oxygen under photoexcitation,and is an antibacterial agent integrating natural antibacterial agent and photodynamic antibacterial.In summary,the BC&o-NBA@ZIF-90 nanoassembly is a new type of photoexcited antibacterial material,and our research has also provided a new way for new antiresistant bacteria drugs and materials.?3?Amantadine?Ad?was conjugated with BODIPY to form a new compound BOD-Ad.It is found that BOD-Ad can self-assemble with BSA forming a non-emissive nanoassembly?BOD-Ad@BSA?.It was found that copper ions can induce BOD-Ad@BSA to release BOD-Ad and restore the fluorescence of the system.In addition,we found that BOD-Ad@BSA can distinguish between free copper?II?and protein-copper?II?complexes,which was first reported internationally.Furthermore,BOD-Ad@BSA was used for the detection of the free Cu²⁺content in fish samples bought from a supermarket.Therefore,BOD-Ad@BSA is a turn-on fluorescent probe for free copper?II?.?4?A fluorescent assembly?BOD-Ad-Cmyc@BSA?was synthesized by combining BOD-Ad with Cmyc G-quadruplex and BSA.The structure was characterized by TEM and CD.It was further used to detect E.coli.The results indicate that BOD-Ad binds to Cmyc to form a fluorescent quencher which can be further assembled with BSA to obtain a fluorescent nanoassembly BOD-Ad-Cmyc@BSA.Cu²⁺can quench the fluorescence of the nanoassembly,while E.coli can capture Cu²⁺to restore the fluorescence of the system.Therefore,BOD-Ad-Cmyc@BSA can be used as a fluorescent probe for detecting E.coli with a minimum detection limit of 6.3 CFU/mL.The BOD-Ad-Cmyc@BSA fluorescent nanoassembly is expected to be used to detect E.coli in the environment or in food.