Design, Synthesis And Cell Imaging Application Of Amphiphilic Rare Earth Complexes

As compared with organic fluorescent dyes,the luminescent rare earth(europium,terbium)ion organic complexes displayed unique optical properties,such as large Stokes shift and specific and sharp fluorescence emission,which endow their important roles for biomedical applications(e.g.,ion detection,biomarker,and visible drug delivery).Especially,the fluorescence lifetime,fluorescence intensity and quantum yield will greatly improve after these rare earth ions were coordinated with organic ligands with matching energy levels.Unfortunately,the natural hydrophobicity and low biocompatibility of rare earth complexes will great restrict their utilization in biomedical fields.On the other hand,to achieve excellent fluorescence properties of rare earth ions,they are required to complex with the organic ligands with matching their energy levels.However,most of organic ligands used currently are lack of reaction sites,and complex and multi-step organic reactions are needed to obtain desirable organic ligands with functional groups for subsequent reactions.Therefore,the exploition of new organic ligands with specific functional groups and development of simple,rapid and effective methods for fabrication of rare earth ion organic complexes-based fluorescent probes with well water dispersibility and low toxicity is of some significance.In this thesis,we fabricated three water dispersible rare earth ion organic complexes-based fluorescent nanparticles via different strategies and the size,morphology,fluorescence properties of these fluorescent nanoparticles as well as their biocompatibility and fluorescent imaging performance were investigated in details.The main research results are as follows:(1)In the first chapter,we reported a convenient and efficient method for fabrication of amphiphilic europium complex-based fluorescent copolymers through using hexachlorocyclotriphospharonitrile as the linkage and its potential for biological imaging was also evalulated.In brief,the europium complex with amino active group was prepared by the coordination of europium trichloride hexahydrate,α-thiophene trifluoromethoacetone and 5-amino-1,10-phenanthroline by thermal precipitation method.Then,the europium complex with active amino group was conjugated with biocompatible amino group-terminated polyethylene glycol(PEG)under ultrasound-assisted conditions via hexachlorocyclotriphosphazene.The amphilic europium complex-based fluorescent copolymers composited with hydrophilic PEG and hydrophobic europium complex were obtained.The results demonstrated that the europium complex-based fluorescent copolymers could selfassemle into fluorescent nanoparticles,which showed high water dispersibility and low cytotoxicity.Moreover,the fluorescent nanoparticles could emit intense fluorescence and high photostaility.The above features endow their great potential for biological imaging.(2)The organic ligand with best matching energy level of terbium ion is acetyl acetone,however this ligand is absent of reaction site,and further complex and multistep organic reactions is required to fulfill the requirements for future applications.In the second chapter,one of aromatic acid sulfosalicylic acid with highly matched energy level with terbium ion was selected as the first ligand,after coordination with the second ligand,the sulfosalicylic acid-based terbium complex could emit strong green fluorescence by thermal precipitation method.Because sulfosalicylic acid has phenolic hydroxyl,we prepared the amphiphilic terbium complex-based copolymers by linking the sulfosalicylic acid-based terbium complex and hydrophilic amino group-terminated PEG using hexachlorocyclotriphospharonitrile with the assistance of ultrasonic treatment.The ultrasonic reaction conditions are mild and no catalyst is required except triethylamine(TEA).The results suggested that the terbium complexbased fluorescent probe displays good fluorescence properties and can be utilized for fluorescent imaging in cells.(3)In the third chapter,we synthesized biodegradable polymers with amphiphilic europium complexes by Raft polymerization.Firstly,polymerizable 1,10-phenanthroline derivative was synthesized,and then poymerizable europium complex was obtained by thermal precipitation method.Finally,the target product was obtained by Raft polymerization using PEG-containing macromolecular chain transfer agent.The experimental conditions for Raft polymerization are mild,controllable and therefore Raft is the best choice for the preparation of polymeric materials.Herein,the amphiphilic europium complex-based copolymers will selfassembly in aqueous solution and form fluorescent nanoparticles with hydrophobic europium complex as the core and hydrophilic PEG as the shell.Therefore,these fluorescent nanoparticles can be well dispersed in water,and applied in biological systems.