Design,Synthesis And Application Of D-A Fluorescent Probe

Fluorescent probes play an important role in the detection of thiols(Cys/Hcy/GSH)in organisms,and have high specificity and sensitivity.Generally,the abnormal levels of these biothiols are associated with many diseases,such as leukocyte loss,psoriasis,liver injury,cancer and AIDS.Therefore,it is of great scientific significance to detect the concentration of biothiols for the prevention and diagnosis of diseases,physiological and pathological research.Based on the recognition mechanism of fluorescent probe,we designed a fluorescent probe with donor(D)and acceptor(A)configuration,The donor and acceptor moieties in the fluorescent probes can adjust the electronic effect of the molecules,which further changes their optical properties.Therefore,new D-A fluorescent probes can be designed by modifying the donor and acceptor groups.In the fisrt work,a series of D-A fluorescent molecules based on pyridine salt and Hydroxy substituted benzaldehyde were designed and synthsized.The optical properties of these fluorescent molecules were studied by adjusting the electronic groups and their positions of the donor and acceptor groups.The results indicated that the fluorescence probe having para hydroxyl sites displayed the strongest fluorescent emission through changing of hydroxyl positions,and the optical fluorescent intensities also could be affected with changing the number of hydroxyl.While with the changing of the electron-withdrawing abilities and positions of acceptor groups,the fluorophores showed weaker fluorescent intensity followed with redshifts.In the second work,we designed and synthesized a two channel D-A type fluorescent probe for biothiols by using Oxaanthropyridine salt(XA)as near-infrared fluorescent moiety and 4-nitrobenzo[c][1,2,5]oxadiazole(NBD)as green fluorescent part.The results indicated that NBD-XA could specifically recognize GSH/Hcy/Cys.With the changing of excitation wavelength,Hcy could be specifically recognized at 560 nm,while GSH/Hcy/Cys could be specifically recognized at 744 nm.The experimental data of sensitivity,anti-interference and cell imaging demonstrated that the probe had good detection ability for GSH/Hcy/Cys.Through the analysis of high-resolution mass spectrometry and optical properties,it is speculated that the recognition mechanism of the fluorescent probe is based on the Nucleophilic substitution reaction and cyclization reaction between GSH/Hcy/Cys and the probe molecule,and then release the fluorophore,thus recovering the intramolecular charge transfer process to realize recognition.In the third work,we designed and synthesized several indanone-containing D-A type fluorescent molecules.We firstly synthesized the probe IND-Py by introducing morpholine moieties as lysosome-targeting site,malononitrile as acceptor part,hydroxyl as donor group,and acryloyl chloride as recognizing site.The optical date demonstrated that the fluorescence intensity of IND-Py and its precursor were weak,which could be resulted from the introduction of morpholine ring and malononitrile.Next,we synthesized NIR-IND by introducing oxaanthracene ring directly on the basis of 5-hydroxyindanone and using acryloyl chloride as the recognizing site.The optical spectra showed that both fluorescent molecules and probes had good fluorescence properties,but the intensity ratio made them unable to be applied as fluorescent probes.