Design And Synthesis Of Novel Fluorescent Dyes And Their Properties And Applications

Fluorescent dyes with excellent photophysical property play important roles in the development of fluorescence imaging.Therefore,it is of great significance to synthesize novel fluorescent dyes with high quantum yield,good stability and deep-red emissions.In this thesis,we rationally designed and synthesized a series of novel coumarin with aggregation-induced emission,xanthene derivatives to detect selenol and rhodamine for lysosomal pH tracking.The details are as follows:(1)An efficient strategy to design novel N,O-chelated boron complexes with aggregation-induced emission and large Stokes shift was developed.The coumarin-based boron complexes HBN and MBN emit strongly in THF because of the inhibition of C=N isomerization in ligands.In particular,the complexes displayed redshifted emissions(>60 nm)in mixed solvents of CH3CN and water because of J-aggregation,which is associated with the intramolecular and intermolecular reaction.Cell imaging experiments indicated that the complexes have good membrane permeability and can be used as lysosome trackers.(2)We designed and synthesized one novel xanthene fluorescent dye O-hNR,The QYs of O-hNR determined is 17.35%in water and the optical properties in aqueous solution of different pH were investigated.Fluorescent probe O-hNRSel which detected selenol was synthesized based on O-hNR with 2,4-dinitrobenzenesulfonyl ester as a recognition site.O-hNRSel can react with Sec rapidly,but not with cysteine in PBS buffer.The experiment data showed that the emission intensity centered at 624 nm of fluorescent probe increased 124-fold after addition of Sec.Cell-imaging experiments indicated that O-hNRSel can be applied to determinate intracellular selenol.(3)The development of near-infrared fluorescent probes with low pKa,high selectivity,high photostability,and high sensitivity for lysosomal pH detection is of great importance.In the present work,we developed a novel nearinfrared lysosomal pH probe(Lyso-hNR)based on a rhodamine derivative.Lyso-hNR showed fast,highly sensitive,and highly selective fluorescence response to acidic pH caused by the H+-induced structure changes from the nonfluorescent spirolactam form to the highly emissive open-ring form.Lyso-hNR displays a significant fluorescence enhancement at 650 nm(over 280-fold)from pH 7.0 to 4.0 with a pKa value of 5.04.Live cell imaging data revealed that Lyso-hNR can selectively monitor lysosomal pH changes with excellent photostability and low cytotoxicity.In addition,Lyso-hNR can be successfully used in tracking lysosomal pH changes induced by chloroquine and those during apoptosis.All these features render Lyso-hNR a promising candidate to investigate lysosomeassociated physiological and pathological processes.