The Synthesis And Biological Exploration Of Benzothiadiazole Derivatives

Benzothiadiazole is a heteroyclic compound with strong electron/light absorbing character and excellent photochemical stability.Benzothiadiazole derivatives have been widely applied in biosensing and bioimaging,solar cell,organic light-emitting diode and so on.The relationship bewtwen structure,performance and application of benzothiadiazole derivatives need to be further studied.In this paper,four benzothiadiazole derivatives were designed and synthesized through connecting different substituents to adjust the molecular structure.The optical properties of them were investigated in detail.Moreover,the applications of these derivatives in bioimaging,and detecting and real-time monitoring bioactive small moleculeswere studied.The main research contents were as follows:1.Two benzothiadiazole derivatives（named as TBDP and TBDT）were designed and synthesized with triphenylamine group as electron donor,benzene/thiophene ring asπbridge to link malononitrile unit.The fluorescence emission band was centered at 605 nm for TBDP and 620 nm for TBDT.Compared with TBDP,the introduction of thiophene group（TBDT）may improve the electronic mobility and light-trapping ability,which can also reduce the energy gap between the highest occupied molecular orbit（HOMO）and the lowest unoccupied molecular orbit（LUMO）resulting in red-shifted absorption and emission band.TBDP/TBDT can realize,turn on"response to Cl O^-in water medium with high selectivity,high sensitivity and fast response time.Fluorescent quantum yields（（37））of TBDP and TBDT in THF solution were 4.82%and 4.66%,respectively.Upon the addition of Cl O^-,the（37）values were lightened to 48.76%and 34.77%,respectively.The LOD value was calculated as low as 75 n M and 33 n M for TBDP and TBDT.TBDT can also effectively visualize trace amount of Cl O^-in living He La cells.2.A D-A type benzothiadiazole-pyridine derivative（PDB）was designed and synthesized using benzothiadiazole as the core which was linked with triphenylamine group as electron donor,pyridine group as electron acceptor with4-（bromomethyl）benzeneboronic acid at N-site of pyridine.PDB exhibited AIE property,whose emission band located at 656 nm.In THF-H₂O medium,PDB can realize“turn on”response to Cl O^-（the fluorescence intensity increased by 31 times）with high selectivity,high sensitivity（LOD=26 n M）and fast response time.PDB can not only monitor trace exogenous Cl O^-expression in Hep G2 cells,but also monitor the transfer process of PDB-Cl O^-system s from mitochondria to lipid droplets.The results of this chapter have potential application value in monitoring evolution process of some related diseases.3.TD-DFT quantum calculation was performed to predict and/or illustrate the electron cloud density distribution,electronic transition,the related absorption and emission maxima of a series of pyrrole-difluoroboron derivatives.Upon the calculated results,a D-A-π-A"type benzothiadiazole derivative（abbreviated as TPBD-BP）was designed and fabricated by triphenylamine group as electron donor and pyrrole-difluoroboron unit as electron acceptor.The fluorescence of TPBD-BP at solid state was centered at 932 nm,which was 985 nm for TPBD-BP nanoparticles encapsulated in PEG-6000（named as TPBD-BP dots）.The fluorescence of TPBD-BP in both solid state and dots exhibited off-peak tail emission,extending to 1300 nm（NIR-II region）.TPBD-BP dots showed excellent water solubility,biocompatibility and aggregation induced emission（AIE）,which was suitable to be applied in in-vivo imaging.NIR-II emission signal of TPBD-BP dots can be observed in the reproductive organ of normal nude mice after tail vein injection.This attractive combination of computational and experimental investigation would help to develop small-molecular NIR fluorophores.