Synthesis And Application Of PH And Hypoxic Fluorescent Probes And Near-infrared PH Fluorescent Probes

The content of this dissertation is to design small-molecule fluorescent probes using the characteristics of tumor cell microenvironment.The spectral properties of these fluorescent probes vary with the microenvironment of the tumor cells,enabling imaging and early diagnosis of tumor cells.This paper is mainly divided into two parts:In the first part,we designed and synthesized four pH-based and hypoxic doubleresponse probes based on 1,8-naphthalenediamide,in which the probe 2-3d achieved a dual response to nitroreductase and pH.Under neutral normal conditions,the photoinduced electron transfer(PET)effect of morpholine and nitrobenzene on the fluorophore results in almost no fluorescence of 2-3d(?=0.10).Under normal acidic conditions,morpholine was protonated,only the nitrobenzene moiety produced a PET effect,the system showed moderate blue fluorescence(?=0.11);under neutral hypoxia,overexpressed nitro The nitrobenzene was reduced by the reductase and the domino reaction occurred.The nitrobenzene was partly removed.Only the morpholine moiety produced the PET effect.The system showed moderate-intensity green fluorescence(?=0.10);under acidic and hypoxic conditions,the nitrobenzene moiety After removal,morpholine was also protonated,completely blocking the PET effect,and the system showed strong green fluorescence(?=0.78).Therefore,2-3d achieves dual detection of pH and hypoxia and can be distinguished.In addition,we have found through cell imaging studies that 2-3d can penetrate cell membranes and can be used for dual imaging studies of hypoxia and pH.Near-infrared(NIR)fluorophores have emission wavelengths in the 650-900 nm region and are even higher.They have obvious advantages in the field of biological imaging.For example,reducing the background fluorescence interference of organisms can effectively reduce light scattering and light damage,and improve the organization of the body.Penetration ability and so on.Therefore,in the second part,we designed the lipid-soluble probe Lyso-Cy7 and the water-soluble probe Lyso-Cy7-SO3 with the near-infrared fluorochrome cyanine dye as the parent and the morpholine as the recognition group.By studying their spectral properties,we found that both probes have a better response to pH change,and their pKa were 4.97 and 4.70,respectively.We coimaged the lysosomal probes commercialized by the two probes and found that the probes can be used for the lysosomal localization of the cells.