Design And Synthesis Of Fluorescent Probe Targeting At Mitochondria And Its Research On Application

Mitochondria are important organelles of eukaryotic cells,and play an important role in cellular physiological processes.Understanding of the behavior of mitochondria in live cells is of great significance to elucidate the biological process of mitochondria.Recent researches have indicated that there exists strong connection between the morphology,function of mitochondria and mitochondrial diseases.By utilization of fluorescence micro-imaging techniques,it has become a hotspot to study the relationship between the mitochondrial morphology and function and monitor the biochemical during the biological process.Fluorescence microscopic imaging is the most key technology is the development of fluorescent probe.Commercial mitochondrial probes generally have several defects such as large cytotoxicity and poor ability to resist photo bleaching.Therefore,it is very urgent and important to design and synthesis mitochondrial targeted fluorescent probes with light fastness and good biocompatibility for real-time monitoring of mitochondrial morphology and understanding of the function and role of mitochondria in the cells.These probes could play significant roles in the early diagnosis of diseases related to mitochondria.This thesis divided into five chapters:The first chapter:This chapter detailly introduced the function of mitochondrial,mitochondrial related diseases,and the research progress of mitochondrial probes.The second chapter:F16 is fluorescent mitochondria-targeted antitumor agent.However,its application in mitochondria imaging has been largely restricted to its cytotoxicity.In this chapter,we synthesized two fluorescent probes(F16-4C and F16-BODIPY)with low toxicity by modification of F16.Our data shows that F16-4C is not suitable for fluorescent imaging of mitochondrial due to its low quantum yield.F16-BODIPY,which contains fluorescent groups,could be used in mitochondrial imaging.However,F16-BODIPY is poorly soluble in water and its cellular uptake rate is low.The third chapter:In this chapter,we synthesized a mitochondrial targeted fluorescent probes TPP-BODIPY by combining BODIPY with triphenylphosphine.This fluorescence probe benefits in stability,high quantum yield,strong anti-photobleaching capability and low cytotoxicity.The probe is an excellent mitochondria-targeted fluorescent probe,and be could potentially used in commercial.The fourth chapter:In this chapter,we synthesized a fluorescent probe TEA-BODIPY by modifying BODIPY with water soluble group triethylamine.Compared to F16-BODIPY and TPP-BODIPY,TEA-BODIPY is highly water soluble and could be uptake by cells efficiently.TEA-BODIPY takes advantage of its high stability,high quantum yield,strong anti-photobleaching capability and low cytotoxicity.The probe is an excellent mitochondria-targeted fluorescent probe,and be could potentially used in commercial.The fifth chapter:In this chapter,we synthesized a series of probes with DLCs structure(Pyridine-4C-BODIPY,Pyridine-7C-BODIPY,Pyridine-12C-BODIPY).However,these probes did not localize in mitochondria.We computed the charge distribution of these probes and propose a new theory on the structure-activity relationship between molecular structure and mitochondrial targeting efficiency.The sixth chapter:The study of the thesis was summarized in this chapter.And the future developments and our opinion of the mitochondrial targeted imaging probes and the mitochondrial targeted antitumor drugs were proposed.