Design, Synthesis And Application Of Near-infrared Fluorescent Probes Based On Coumarin Skeleton

Multifunctional organic small molecular fluorescent probes provide powerful tools to visualize subcellular microstructures and monitor subcellular dynamic functions,which significantly boost our understanding of complex biological phenomena and manipulation of biological behaviors regulation.However,realization of diverse biological applications from a single molecular backbone is still a challenging endeavor.Based on the coumarin skeleton,a series organic small molecule fluorescent probes were synthesized by reasonable molecular design,and their applications in biological imaging,diagnosis and treatment were further studied.Specific research contents are as follows.In the first part,we designed and synthesized a series of coumarin-based fluorescent probe Cou-n(n=1?4)with pyridine salt group.This series of compounds not only exhibit near-infrared fluorescence emission property(675 nm)and large Stokes shift(110 nm),but also have excellent biocompatibility.Changing the length of the alkyl side chain on the pyridine salt group can regulate the lipophilicity of the compound and thus adjust the ability of the probe to target the subcellular structure.Cou-1,which has a shorter alkyl side chain,can be used for ultrafast staining of cell membrane within 10 s.In addition,Cou-1 is sensitive to the change of plasma membrane potential.With the decrease of plasma membrane potential,the fluorescence signal of Cou-1 is gradually weakened,which enabled Cou-1 to indicate the cell passage number successfully.The probe with longer alkyl side chain Cou-3 can selectively target mitochondria and realize ultrafast staining of mitochondria within 30 s.Cou-n can also produce singlet oxygen under white light.Due to the specific mitochondrial targeting ability and efficient singlet oxygen production performance,Cou-3 exhibits high-efficiency photodynamic therapy effect and good tumor growth inhibition effect.Furthermore,the appropriate lipophilicity is helpful for Cou-3 to selectively image Gram-positive bacteria and can eliminate Gram-positive bacteria by PDT process.In the second part,two coumarin aldehydes Cou-CHO and Cou-S were synthesized by introducing di-p-tolylamino group into the coumarin skeleton,and compounds CouMa,CouFu,CouTCF,CouSMa,CouSFu and CouSTCF were synthesized by introducing different electric-absorbing groups subsequently.The aggregation-induced emission(AIE)properties of CouMa,CouFu and two intermediates were preliminarily investigated,and the results showed that they all had AIE properties,and the maximum emission wavelength of CouMa and CouFu was located in the near infrared region(725 nm and 770 nm),which laid a foundation for the design,synthesis and application of the near infrared AIE materials.