Rare Earth Organic Complexes Containing Heterocyclic Ligand Synthesis, Characterization And Biological Activity

In recent years, the study of metal complexes on antibacterial, antitumor and with DNA interaction have played importment role in the bioinorganic chemistry .On the biological properties of RE³⁺, twenty-five earth complexes with heterocyclic compounds and other ligands were synthesized by reflux condensation method and low temperature solid phase method.Their composition and structure werecharacterized by elemental analysis, molar conductance, IR, UV, 1HNMR, XRD and TEM etc. The stability of heat was proved by the data of TG-DTA. Some complexes were synthesized by low temperature solid phase method ,which was greener method without using any solvent.The compositions of the complexes containing nitrogen heterocyclic ligands were confirmed to be:Ln₂(ADP)(H₂O)2Cl3 and Ln3(ADP)(MoO4)2(CH₃OH)4Cl5•2H₂O (Ln=La³⁺,Sm³⁺,Pr³⁺,Nd³⁺,Y³⁺,Er³⁺;ADP=2-Amino-4,6-dimethoxypyrimidine); La2(ADMP)(H₂O)2Cl3 and La2(ADMP)(MoO₄)2(CH₃OH)3Cl₆•2H₂O(ADMP=2-A mino-4,6-dimethylpyrimidine);La2(AP)(H₂O)2Cl3 and La₃(AP)(MoO₄)₂(CH₃OH)₄Cl₅ (AP =2-Aminopyrimidine).The compositions of the complexes containing sulfur heterocyclic ligands were confirmed to be:Ln (TTA)3L] •H₂O (Ln = La³⁺, Ce³⁺, Nd³⁺, Eu³⁺, Er³⁺, TTA= Thenoyltrifluoroacetone anion , L= p-chlorbenzoicacid) ; La(TTA)3N ( TTA= Thenoyltrifluoroacetone anion,N=4-Hydroxybenzoic acid).The compositions of the complexes containing both nitrogen and sulfur heterocyclic ligands were confirmed to be:La(TTA)₃(Hbiim)( Hbiim=2,2-Biimdazole,TTA=Thenoyltrifluoroaceton anion),La(L)phen(NO3)3C₂H₅OH•CH₃OH(HL= Shiff Base,phen = 1,10-Phenanthroline ), and another complex was La(Hbiim)3N (Hbiim=2,2-biimdazole, N= 4-Hydroxybenzoic acid ).The antibacterial activities of the complexes were evaluated by the agar diffusion method and nutrition broth dilution method. The results indicated that all the complexes exhibited antibacterial activities against Escherichia coli and Staphylococcus aureus, their antimicrobial spectrum were broad and have durable quality. In the complexes containing nitrogen heterocyclic ligands, the antibacterial activity test indicated that the complexes showed better antibacterial activity against Escherichia coli than Staphylococcus aureus, and binary complexes showed better antibacterial activity than ternary complexes.At the same time,the antibacterial activity were moderate(10-20mm). In the complexes containing sulfur heterocyclic ligands, the antibacterial activity were good(>20mm). In the two complexes containing both nitrogen and sulfur heterocyclic ligands, the antibacterial activity were also good(>20mm). The antibacterial mechanism of the complexes was discussed preliminarily in this paper.The antitumor activity of some complexes against K562 tumor cell in vitro were researched by morphological observation, MTT assay and Flow Cytometry. The results showed that these complexes all could induced K562 tumor cells apoptosis and inhibited their growth,but the cell apoptosis rate and the inhibition rate both higher than their ligands and have concentration-dependent and time-dependent. The median inhibitory dose (IC50) of the complexes were below 10μg/mL.The IC50 of the complexes containing nitrogen heterocyclic ligands were between 110μg/mL, and ternary complexes showed better anti-tumor activity than binary complexes. The IC50 of the complexes containing sulfur heterocyclic ligands were between 15μg/mL. The IC50 of the complexes containing both nitrogen and sulfur heterocyclic ligands were between 15μg/mL.The complex La(TTA)3L•H₂O has induced K562 tumor cell for 48h can effect best apoptosis power, and effect S period.At the same time, the anti-tumor mechanism of the complexes was discussed preliminarily in this paper.The interaction of the complex La (TTA)3L•H₂O with DNA were studyed by UV, fluorescence spectrum and agarose gel electrophoresis etc.The results indicated that the interaction of the complex would bind DNA mainly by partially intercalation and the complex could cleave pBR322DNA effectively,but has concentration-dependent.The best concentration of cleaving pBR322DNA was 0.1mmol•L-1.