Studies On Design,synthesis And Biological Activity Of Al³⁺,Zn²⁺ Fluorescent Probes And Cu²⁺ Complexes

Aluminum is the non-essential element in human body.In recent years,more and more researches show that the aluminum ions will bring significant harms to human health in the presence of high concentration in human life and environment.Zinc is the second most abundant transition metal ion;recent studies have shown that failures in zinc homeostasis are associated with neurological diseases.Therefore,it’s very important to find a probe that tracking and detecting the metal ions with high selectivity and sensitivity.On the other hand,with the development of anticancer platinum drugs and a wide range of clinical application,metal complexes with anticancer and antibacterial properties have attracted more and more attentions,but the disadvantages of platinum drugs,such as high toxicity and drug resistance,urged the reseachers to find high efficiency and low toxicity complexes to replace the platinum drugs used in clinic,it is important in the field of biological sciences.Obeject:Synthesis a series of aluminum and zinc ion fluorescent probes based on schiff base and benzothiazole compounds,to study the influencing factors of the fluorescence intensity,such as solvent effects and structure-activity relationship,and screen out the best Al³⁺or Zn²⁺fluorescent probe.On the other hand,design and synthesize novel taurine-like copper complexes,study their inhibiting effect on tumor cells and the interaction between complexes and DNA,hope to find the alternative metal complexes as antitumor drug.Methods:According to previously reported procedure,synthesize a series of aluminum or zinc ion fluorescent probes based on aromatic Schiff base and benzothiazole derivatives,various methods such as IR,UV,fluorescence spectroscopy,¹H-NMR,and mass spectrometry were used to investigate the fluorescent effects while interacting with Al³⁺or Zn²⁺ion.Two novel Cu²⁺complexes based on taurine-like ligands have been synthesized and characterized by elemental analysis,IR and single-crystal X-ray diffraction.The interaction of complexes with DNA was investigated by UV-Vis,fluorescence spectra,viscosity,gel electrophoresis assays;and MTT assay was carried out to study the cytotoxicity on different tumor cell lines.Result:Successfully synthesized 13 aromatic schiff base and benzothiazole ligands,L¹～L¹³.By comparing the molecular structures of different probes and their fluorescence intensity while reacting with aluminum or zinc ions,L⁶ and L⁹ were screened out with the excellent fluorescent sensor property.At first,we took L⁶ as the aluminum ion probe to study the fluorescence characteristics.L⁶ can specifically identify Al³⁺and can produce a strong fluorescence in methanol solvent.Moreover,L⁶ detecting Al³⁺has less interferce from other common metal ions showing many advantages,such as high sensitivity,good stability,good linear relations between fluorescence intensity and[Al³⁺]in a certain range of concentration.According to the result of Job’s plot curve fitting,¹H-NMR,MS data,coordinating ratio of L⁶ and Al³⁺is 1:1 in L⁶-Al³⁺solution.Through SAR analysis between ligands and fluorescence intensity,we discussed the mechanism of L⁶ combined with Al³⁺,and explored the application value of the Al³⁺sensor.Secondly,we took ligand L⁹ as a Zn²⁺probe to make a further research,discussed the feasibility of benzothiazole derivatives as sensors to recognize zinc ion,presenting a new idea for developing metal ion probe.Thirdly,two novel taurine-like Cu²⁺complexes have been synthesized and characterized by a variety of methods.In the discrete mononuclear structures of 1 and2,the copper core is five-coordinated and presents a distorted trigonal bipyramidal geometry structure.The interaction of complexes with CT-DNA was investigated by UV-Vis,fluorescence spectra and viscosity;the data reveal that 1 and 2 binded to CT-DNA by a partial intercalation binding mode.Gel electrophoresis assays demonstrate that these two complexes have efficient oxidative cleavage of supercoiled DNA in the presence of H₂O₂,and MTT assays indicated that both 1 and2 showed significant cytotoxicity towards human hepatoma cell,Hep G-2.Conclusions:In the first part of this thesis,by comparing structure activity relationships of eight salicylaldehyde Schiff base ligands（L¹-L⁸）,L⁶is an excellent aluminum fluorescence probe with high sensitivity,selectivity,stability,fast response,excellent linear relationship which can be used to quantitatively detect the concentration of aluminum ions.In the second part,by comparing structure activity relationships of five ligands(L⁹-L¹³),L⁹and L¹³ were selected as metal ion probes to analyzing and discussing the fluorescent mechanism based on the benzothiazole derivatives,providing certain useful informations for the structure modification of metal ion fluorescent probe.In addition,TSSB as znic ion probe showed the good water solubility,indicating that salicylaldehyde schiff base has the feasibility to be a metal ion probe;these results provide new ideas for improving the water solubility of schiff base fluorescent probe.In the third part,two novel mononuclear Cu²⁺complexes with new taurine-like unsymmetrical tripodal ligand have been synthesized and characterized.Partial intercalation between complexes and CT-DNA was confirmed by using various spectroscopic methods and viscosity measurement.Compared to the other copper complexes reported in literature,complexes 1 and 2exhibited a moderate binding affinity with DNA,probably owing to the planarity of imidazolyl or pyridyl ring and the steric hindrance from tripodal ligands.Both 1 and 2displayed effective oxidative DNA cleavage activity in the presence of external agents H₂O₂.Moreover,they both showed significant cytotoxic activity toward the Hep G-2cell lines,and the IC₅₀ values of 1 and 2 are considerably lower than the clinically-used cisplatin under in vitro conditions.The results from our present study suggested that both 1 and 2 deserve further investigation as new potential antitumor drugs.