Design And Synthesis Of Organelles Targeting Novel Fluorescent Dyes For Cell Imaging

Fluorescence analysis is an important and sensitive analytical technique,which has been widely used in the fields of environmental science,materials science,medical pharmacy and cell biology.We can utilize fluorescent probe with various functional groups to visualize small biomolecules,neutral molecules,metal ions,anions,organelles such as lysosomes,mitochondria and endoplasmic reticulum by cell imaging,which can reveal physiological and pathophysiological pathways.To meet different analytical and research needs,it is in need to develop a variety of fluorescent sensors.In this thesis,three types of fluorescent probes were designed and synthesized:fluorescent probe for sulfur dioxide derivative,fluorescent probe for Cys and lysosomal targeting fluorescent dyes.This thesis contains five chapters:The first chapter summarizes the literature,introduces the common characteristics of fluorescent probes,design principles and research progress of sulfur dioxide derivatives and biothiols probes.In the second chaper,we reported a colorimetric and ratiometric fluorescent probe CZBT for the detection of HSO₃^-with high selectivity and low detection limits?28 nM?.This probe has been used to determine the level of HSO₃^-in several real environmental water samples?snow water,industrial wastewater?and has a good recovery.Cell staining results show that the probe is membrane permeable and mitochondrial targetable and can be used to monitor the level of intracellular HSO₃^-.In the third chaper,we reported a near-infrared fluorescent probe based on NIR-BODIPY and NBD for multicolor detection and imaging of Cys.Through nucleophilic substitution reaction and intramolecular rearrangements,Cys induced the probe to produce fluorescence-enhancement responses in the green and near-infrared channels.This probe allows rapid determination of Cys with high selectivity and low detection limit?22 nM?.In addition,fluorescence imaging of HeLa cells indicates that the probe can be applied to multicolor imaging of intracellular Cys with good cell membrane permeability and low cytotoxicity.In the forth chapter,we synthesized a series of lysosomal-targeted BODIPY fluorescent dyes,Lyso-green,Lyso-red and Lyso-NIR,which displays green to near-infrared emission.These compounds have excellent photobleaching resistance in organic solvents.Cell staining experiments showed that these BODIPY derivatives have low cytotoxicity in living cells,good cell membrane permeability and excellent photobleaching resistance.Most importantly,these BODIPY derivatives are specific lysosomal targeting dyes with green to near-infrared emission fluorescence.The fifth part concludes the paper,summarizes the experimental results of the thesis.