Design,Synthesis And Application Of Several Novel Small Molecules Fluorescent Probes

Iron,glutathione(GSH)and Cys(cysteine)are essential ion and amino acids which exist widely in the human body,and play pivotal roles in the normal physiological activities of the human body.The liver damage,diabetes,cancer and other diseases will be accompanied by the changes of their concentration.Because of its advantages of fluorescence probe technique such as structural controllability,strong targeting and real-time in situ imaging,it is becoming one of the most effective methods to monitor the above three kinds of components.However,there are still some difficulties in this field,such as poor relative selectivity,low sensitivity and narrow monitoring range,so,in this paper,five kinds of new small-molecule fluorescent probe were designed and synthesized to detect the Fe3+,GSH and Cys,and further evaluated their applications in human cells,to provide new strategies and methods for the detection of these three substances.The main research contents of this thesis are listed as follows:(1)Based on the fluorescence resonance energy transfer(FRET),ethylenediamine was used for the molecular chain of connection which connected the chromophore of Rhodamine B and IR780,we established a new fluorescence probe for detection of Fe3+.The spectral performances including pH stability,selectivity,response time and quantitative analysis were investigated by UV-vis absorption and fluorescence spectroscopy.The results showed that the sensitivity of the IRRDM was comparable with those reported Fe3+ probes,and the range of detectable concentrations(0.11-135μM)was wider than that of existing ones.More importantly,it can specifically discriminate Fe3+ from other ions.Additionally,taking oxygen,sulfur and nitrogen atom of the open loop of maleic anhydride and 4-aminobenzothiazole as potential ligands,a new fluorescent probe(RDBSF)was designed and synthesized to develop a chemosensor for detection of the Fe3+ ion.Photochemical characterization showed that RDBSF exhibited higher selectivity and sensitivity toward Fe3+(0.01 μM)than those of reported literatures,and remedied the deficiency of IRRDM probe in the detection limit.(2)Based on the mechanism of Michael addition reaction and donor-excited photo-induced electron transfer,a new fluorescent probe(RDMBM)was designed and synthesized toward the detection of GSH.The spectral changes exhibited that RDMBM showed a specific selectivity toward GSH(0.30-500 μM),and improved poor selectivity of GSH in current reports.Similarly,on the basis of the coordination of the probe to Ir3+ and GSH,a new probe(IRPSM)for detection of GSH was synthesized and designed.The spectroscopic studies showed that the fluorescence of IRPSM was rapidly quenched by Ir3+.As a consequence,we designed two ways to discriminate GSH from other amino acids.The results showed that the detection order which was IRPSM,GSH and Ir3+ exhibited a high selectivity and sensitivity towards GSH(0.04 μM),it made up for the defects of RDMBM probe which had wide concentration range,and low sensitivity for GSH.(3)Depending on the reaction of Michael addition and acylation,we designed and synthesized a novel chemosensor(TRDM-F)for detection of Cys.Photochemical studies showed that the fluorescence of TRDM-F can be controlled by fluorescein chromophore,and displayed a high selectivity,sensitivity(0.09-270 μM)and wide range concentrations towards Cys over the performance of the reported literatures.(4)Benefited from the above progressive experimental results,confocal fluorescence microscopy imaging was carried out in HepG2 or Hela cells,which demonstrated that the above five new probes could be successfully applied in discrimination of Fe3+,GSH and Cys in cells,and held great potential in biological application.