The Synthesis,Characterization Of Boron Dipyrromethene (BODIPY) Derivative And Nano-composites And Recognition Of Metal Ions And Celluarimaging

Fluorescent probes have the advantages of high sensitivity,simple technology and short response time,which are widely used in the field of analytical sensing and optical imaging.BODIPY?4,4-difluoro-4-bora-3a,4a-diaza-s-indacene?compounds have attracted many attention due to their high fluorescence quantum yield,molar extinction coefficient,good light stability and unique optical properties.The structure of BODIPY can be modified with different functional groups to obtain the BODIPY fluorescent dyes with excellent properties.NIR-BODIPY with strong absorption could be used for fluorescence imaging in vivo.Therefore,BODIPY fluorescent probes have potential applications in imaging,diagnosis and treatment of tumors in vivo.It is crucial for the development of tumor diagnosis and treatment to design and synthesis NIR-BODIPY derivative.In addition,exploring the interaction between BODIPY with?-cyclodextrin and other guests to develop a novel BODIPY fluorescent nanocomposite with good water solubility and biocompatibility are expected to be used for imaging of biological subcellular organelle.The research progresses of BODIPY compounds,fluorescence probes based on BODIPY reaction and near-infrared BODIPY fluorescent sensor for metal ion were systematically summarized in this thesis.Six new BODIPY compounds and two nanocomposites were designed and synthesized.The structures of the compounds and nanocomposites were characterized by NMR,ESI-MS,IR,UV and TEM.In addition,the subcellular imaging of nanocomposites and the inhibition of tumor cells were studied.Moreover,the recognition of metal ions by near-infrared BODIPY derivatives was discussed.The innovative results are as follows:?1?The amantadine-coupled BODIPY derivative BSJ was synthesized.Based on host-guest interactions and hydrogen bond assembly,two different nanoparticles were obtained:BSJ-CD and BSJ-Ps.Optical properties and subcellular imaging of two nanoparticles and their inhibitory effects on tumor cells were studied.It is found that BSJ-Ps nanospheres could be a mitochondria targeting agent for BGC tumor cells.The BSJ-CD nanoparticles show good water solubility and larger Stokes shift?56 nm?,and can image the cell membrane of BGC tumor cells.Moreover,BSJ-Ps have obvious inhibition effect on BGC tumor cells,whereas BSJ-CD with no obvious toxicity to BGC tumor cells in the range of 0-40?M.The results show that the toxicity and subcellular distribution of BODIPY derivatives?host,BSJ?can be changed by assembling with functional molecules?guest,Ps or CD?.BSJ-Ps can be both a mitochondria-targeting imaging agent and an anti-cancer agent,whereas BSJ-CD can be used as low toxicity membrane probes of tumors.The study of nano-BODIPY probes with subcellular targeting and low-toxicity properties will support a new strategy for the research of BODIPY nanocomposites based on self-assembly induced by functional molecule.?2?The side chain modified BODIPY?BPN?was synthesized and characterized.It is found that BPN has NIR emission at 765 nm and has different fluorescence respond to Cu²⁺and Mn²⁺.The interaction of Cu²⁺with BPN result in the formation of[BPN-Cu]²⁺complex with quenched fluorescence,while Mn²⁺induced aggregation of BPN with specific fluorescence enhancement.Moreover,BPN can be applied to monitor Cu²⁺in live cells and mitochondria targeting image.Further,BPN was used as sensor for the detection of Cu²⁺ions in serum with linear detection range of 0.45?M-36.30?M.The results indicate that BPN is expected to be a fluorescence sensor for the detection of Cu²⁺in blood and the level of Cu²⁺in living cells.?3?The click reaction of the BMG?a NIR-BODIPY derivative?and PTAD was discussed for the first time to synthesize the BMP compound.The optical properties of BMP have been studied and found that the addition of PTAD can change the large-conjugation system side chains of BMG with the blue shifted of maximum absorption of BMP from 567nm to 503 nm.It was also found that the increase of temperature could change the structure of pyridazine ring of BMP with fluorescence quenching,and BMP can be a mitochondrial targeted imaging agent of tumor cells.It is expected that BMP could become a new type of biological fluoresent probe with sensitive sensing for temperature change in vivo.