Design,Synthesis And Application Of Viscosity And Large Stokes Shift Mitochondria Targeted Fluorescent Probe

Mitochondria are essential organelles in most eukaryotes,and their main function is to produce energy to participate in a variety of cellular activities in the cell,including growth and differentiation and apoptosis of the cell.Mitochondrial dysfunction can lead to a variety of human diseases,such as cancer,diabetes,and so on.To gain further insight into mitochondria,it is important to probe fluorescent probes for mitochondria.Most of the fluorescent probes for mitochondria are designed based on mitochondrial membrane potential,and these probes are able to detect the changes of various molecular ions within mitochondria,such as SO_2,H₂S.But these probes ignore the change of mitochondrial microenvironment.And the unique functions of mitochondria are closely related to the microenvironment within cells.Therefore,it is important to investigate probes for changes in the mitochondrial microenvironment.In this paper,based on the research status of mitochondria targeted probes,three fluorescent probes for specifically detecting the mitochondrial microenvironment were designed and synthesized.And further investigated their spectroscopic properties and bioimaging applications.（Ⅰ）Developed a fluorescent probe,TP-NSZ,which consists of imidazole analogues as fluorophores and pyridinium salts as sites to localize mitochondria.With the increase of mitochondrial viscosity,the fluorescence intensity of the probe TP-NSZ gradually increased,so the probe TP-NSZ can be used to detect mitochondrial viscosity.This probe was designed to detect changes in viscosity in the mitochondria of living cells.The advantages of this probe include its rapidity of reaction,large Stokes shift and strong specificity.（Ⅱ）We designed fluorescent probe MTS-Z based on bicarbazole fluorophore.This probe has excellent optical properties,including large stokes shift,high photostability and low background fluorescence.View of this,probe MTS-Z can real-time image mitochondria in the living cells and has the potential to be able to be applied to tissues and zebrafish.More interestingly,MTS-Z possessed the ability to track cell apoptosis process based on mitochondria and cell membrane imaging.This will provide a visual tool for real-time tracking of the healing process of major diseases.Furthermore,it will provide important clues for the relationship between mitochondria/cell membranes and major diseases.（Ⅲ）Developed a mitochondrial fluorescent probe,TP-NM,which uses Naphthalimides as fluorophores and pyridinium salts as sites to localize mitochondria.The probe exhibited good selectivity and high sensitivity,and bioimaging experiments showed that TP-NM was able to detect the viscosity changing bodies of mitochondria in living cells.