Design And Synthesis Of D-A-D Scaffold And Small Molecule Based NIR-? Dyes

Fluorescence bioimaging technique has been widely applied for imaging of cells tissues and living subjects,which provides a powerful tool for researchers and surgeons.The fluorescence imaging in the second near-infrared window(NIR-?)has draw a lot of attention because it greatly reduces the interaction between photons and biological tissue.NIR-? fluorescence imaging is demonstrated to improve the accuracy of early disease diagnosis because it improves the poor tissue penetration and low signal-to-noise ratio from the visible and the first near-infrared window(NIR-?).Compared with inorganic nanomaterials,NIR-? organic small-molecule dyes are considered as ideal candidates for clinical translation because of their fast biological metabolism and low toxicity.NIR-?small-molecule dyes with Donor-Acceptor-Donor(D-A-D)scaffold have always been the focus of research in this field due to their good photo stability,large Stokes shift,and easy functionalization.However,the reports on how to regulate the wavelength of these D-A-D dyes through the modification of their structure are still relatively.Herein,after adjusting the wavelength and fluorescence properties of these dyes,a series of D-?-A-?-D NIR-?fluorescent dyes were designed and synthesized by changing the donors and the acceptors.The main research contents are as follows:(1)By introducing electron donor different intensities,we synthesized a series of NIR-? fluorescent dyes with red shift wavelength.Using benzodithiadiazole as a strong electron acceptor;3,4-ethylene dioxythiophene(EDQT)as electron spacer and introducing separately fluorene,carbazole,trianiline and 2-diphenylamine fluorene as donors,the NIR-? small molecule fluorescent dyes SY1030,SY1020,SY1040 and SYL with D-?-A-?-D scaffolds were successfully synthesized by Suzuki coupling reaction.The in vitro studies show that emission spectra of four kinds of small molecule dyes cover NIR-? region,stokes shifts exceed 200 nm.Under the excitation of 808 nm laser,all four small-molecule dyes have NIR-? fluorescence signals.SY1030 still showed strong fluorescence signal for the longer wavelength NIR-? fluorescence imaging under LP1200 nm fl iters.(2)To solve the problem that the ability of donor to change the wavelength was weak,we introduced the stronger receptor benzoselenidazole into the D-?-A-?-D scaffold,which further redshifted the dye wavelength.Using fluorene ring,carbazole and trianiline as electron donors,the electron acceptor of benzothiadiazole was replaced by benzothiadiazole,and the small molecule fluorescent dyes SY1080,SY1100 and SY1090 with D-?-A-?-D scaffold were successfully synthesized by ring-off reaction.The in vitro studies showed that the maximum emission wavelength of the three small molecular dyes was closed to 1100 nm.Compared with benzothiadiazole as the electron acceptor,benzoseladiazole causes the maximum absorption redshift of small molecule fluorescent dye with D-?-A-?-D skeletons to be more than 75 nm and the maximum emission wavelength to be more than 30 nm.Under the excitation of 808 nm laser,all three small-molecule dyes have NIR-? fluorescence signals.They still show a strong fluorescence signal under LP1200 nm fliters,which were suitable for longer wavelength NIR-?fluorescence imaging.