Design,Synthesis Of Near-infrared Squaraine Based Fluorescent Probes For Bioimaging

In recent years,fluorescence imaging technology has become an indispensable and important technology in the field of modern biology,medicine and pharmacy due to its high spatial and temporal resolution,high sensitivity,ability to obtain information in situ,intuitively,and accurately.Fluorescent probes with absorption and emission in the near-infrared(NIR)region(650-900 nm)are more conducive in vivo bioimaging studies with advantages of minimal light damage to biological samples,better penetration of deep tissue and effective reduction of background fluorescence from biomolecules in living systems.In this dissertation,several novel fluorescent probes were constructed based on near-infrared squaraine dyes,which can realize the imaging detection of mercury ions in living cells and zebrafish,selective recognition of BSA with fluorescent and colorimetric dual channels,the construction of fluorescence chemosensing ensemble and logic gates,and fluorescence imaging detection of intracellular ATP.Chapter 1,the research progress of near-infrared organic small molecule fluorescent dyes is briefly introduced.The design principle of the near infrared squaraine fluorescent probe and its application in biosensing and imaging are summarized.Chapter 2,we design and synthesize a monothiosquaraine(MTSQ)dyes based on the thiophilicity of mercury ions.The introduction of hydroxyl groups at the ortho position of the squaraine center four-membered ring can act as a driving force for the desulfurization reaction and increase the rate and specificity of the reaction,which improves the selectivity of the assay.Self-aggregation of squaraine dyes in aqueous solution and the heavy atom effect of sulfur atom effectively reduces the background fluorescence and improves the detection sensitivity of the probe.The probe exhibits excellent properties such as high sensitivity,excellent selectivity,and good biocompatibility,and has been successfully applied to the imaging detection of mercury ions in living cells and zebrafish.Chapter 3,Based on the "aggregation-disaggregation" mechanism,a near-infrared squaraine dye with good water solubility was designed and synthesized.In PBS buffer,the fluorescence was quenched due to aggregation.After the addition of BSA,the interaction between BSA and the dye causes disaggregation and the fluorescence recovers.At the same time,the color of the solution changes from purplish red to light blue,which effectively enables the selective recognition of BSA with fluorescence and colorimetric dual channels.The SQ-2(?)BSA was used for cell incubation and in vitro fluorescence imaging studies.The novel hybrid is expected to serve as a platform for a variety of biological applications.Chapter 4,a near-infrared fluorescent chemosensor based on squaraine has been synthesized,and its cascade recognition for copper ion,biological phosphate PPi,and amino acids has also been investigated by spectroscopic techniques.SQ-4 exhibits high selectivity and sensitivity for sensing Cu2+ over other metal ions by reversibly forming a[SQ-4-Cu2+]complex.By tandem ligand exchange,PPi and amino acids can remove Cu2+ from the complex and restore the spectral signal of SQ-4,which can be used for cascade recognition of these biologically active species.Notably,an IMPLICATION logic gate has be constructed based on this bifunctional chemosensing system.Chapter 5,based the reaction between phenylboronic acid and vicinal diols,near-infrared squaraine dyes(SQ-PBA1-3)with two phenylboronic acid groups were designed.The cationic surfactant cetyltrimethylammonium bromide(CTAB)was introduced to the pH=7.4 PBS buffer,so that the phenylboronic acid group and the cis-diol part in the ATP molecule are more easily combined.At the same time,the combination facilitates the conversion of the dye molecules from the aggregated state to the disaggregated state,allowing fluorescence to be released so that detection of ATP can be achieved.The dye has the advantages of convenient synthesis,good selectivity and high sensitivity to ATP,and has been successfully used in the detection of intracellular ATP and screening for cancer drug.