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Design,Synthesis And Application Of Novel Fluorescent Probes For Viscosityand Hydrogen Sulfide

Posted on:2019-06-10Degree:MasterType:Thesis
Country:ChinaCandidate:C GaoFull Text:PDF
GTID:2371330545950477Subject:Chemistry
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In the past decades,fluorescent probeshaveplayed an important role in a variety of fields,such as chemistry,biology,environment,andmedicine.Fluorescence probe technology has become an important biomedical tool,which is widely used in the biological research of molecules,cells and even organisms.Intracellular viscosity basically controls all diffusion-mediated processes,and abnormal viscosity can reflect dysfunctional state,which is closely related to a variety of diseases.Intracellular viscosity is a potential biomarker for different diseases,and abnormal lysosomal viscosity is a marker of disease,inflammation and even cancer in lysosomes.Therefore,the detection of lysosomal viscosity is of great significance.This paper designs and synthesizes two new kinds of novel targeted lysosomal viscosity fluorescent probes,Lyso-AIE1 and Lyso-AIE2.The probe was based on tetraphenylethene derivatives and two water-insoluble enhancers as the basic skeleton structure,with pyridine or indole as the target group of lysosomes.These two probes are only weakly emissive in nonviscous medium and the emission signals are greatly enhanced in viscous medium due to the restriction of intramolecular motion.the response of the probe of viscosity,the pH stability of the probe and the polarity independence were measured under in vitro physiological conditions.In addition,the ability of Lyso-AIE2 to monitor the viscosity of lysosomes in living cells was also discussed,and the application of cell apoptosis and autophagy under different stimulation conditions was demonstrated.These probes can provide a useful research method for the in-situ and real-time research of lysosomal related physiological and pathological processes.The active sulfur species?RSS?is a common term for a group of sulfur-containing biomolecules in the organism,and the endogenous active sulfur species in the body play a vital role in physiological metabolism.Hydrogen sulfide?H2S?is a common bioactive sulfur species.In organisms,endogenous hydrogen sulfide gas is produced during metabolism,and hydrogen sulfide in the range of physiological concentration is related to many physiological or pathological processes.hydrogen sulfide disorders,whether high or low concentration,are associated with many diseases.Therefore,it is urgent to develop high precision and operable methods to track the production,distribution and transportation of H2S in physiological processes to elucidate the molecular mechanism of physiological and pathological effects.In this paper,based on the reduction property of hydrogen sulfide,we choose naphthalene imide as fluorophore,?Azidomethyl?benzeneas the recognition site,N-aminoethyl morpholineas targeted groups,successfully designed and synthesized a new high selective targeting lysosome hydrogen sulfide fluorescence probe.The probe SN-N3 can detect hydrogen sulfide in living cells with high selectivity and sensitivity.At the same time,the probe SN-N3 has a very large stokes shift?100 nm?and has the advantages of stable pH.In addition,the experiment showed that the probe also had good lysosomal targeting and low cytotoxicity,and was successfully used in living cell fluorescence imaging.Therefore,the probe SN-N3can provide a novel,selective and sensitive detection method for hydrogen sulfide.
Keywords/Search Tags:Viscosity, Lysosome, Aggregation induced emission, RSS, Hydrogen Sulfide, Naphthalene imide
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