Studies On The Synthesis, Characterization And Bioactivities Of The Laminine And Its Schiff Base Complexes

Amino acids are important physiological active substances. Because the aminoacids have the special structure with the atom N and O, so they can react with reactivecorbonyl group to pull different structures and reactive groups in the products. Schiffbase and its complexes are widely used in the fields of catalysis, biology and materialetc. In recent years, many researchers have reported that Schiff base complexes havethe anticancer activity, but the anticancer activities and mechanisms of amino acidSchiff base complexes as proteasome inhibitors and apoptosis inducers are seldomreported. It is a challenging project to design and synthesize different amino acidcomplexes for studying their structures, properties and bioactivities on tumor cells bytargeting cellular proteasome and inducing apoptosis.To adapt to special living situation, most of the marine organisms produce andaccumulate a large number of substances with special chemical structure andbiological activity in their body. Laminine is a small molecule with good bioactivity,obtained from marine organism. It is a kind of non-protein amino acid which hasspecial physiological functions in seaweed, such as lowering cholesterol, reducingblood lipids, anti-platelet condensed and preventing atherosclerosis.In the paper, firstly laminie is productd with L-lysine, then three series ofcomplexes with laminie and Schiff base ligands have been prepared. The ligands andcomplexes are characterized by IR spectrometry, elemental analysis, UV-Visspectrometry,1H NMR and TG-DTG analysis and the possible chemical structures ofthem are inferred. Fluorescence properties of ligands and their complexes are tested.The mode of interaction between [CuL1(CH3COO)2(H2O)]·H2O and CT-DNA isstudied. The inhibition and inducing apoptosis of the cadmium complexes on tumor cells have been also studied by targeting the cellular proteasome.The main works ofthe thesis are shown as follows:(1) Laminine is synthesized with L-lysine as raw material, Zn2+ion as α-aminoground blocker and dimethyl carbonate as methylation reagent.(2) Transition metal complexes with Laminine ligand (L) are synthesized. Thepossible chemical compositions of these complexes are confirmed to be:[ML2(CH3COO)2][M=Cu(II)、Zn(II)、Ni(II)]；[ML2(CH3COO)2]·2H2O[M=Cd(II)、Mn(II)、Co(II)]；[M(phen)L(CH3COO)2]·2H2O[M=Cd(II)]。(3) Transition metal complexes with Schiff base ligand (L1) derived fromO-vanillin and laminine are synthesized. The possible chemical compositions of thesecomplexes are confirmed to be:[ML1(CH3COO)2(H2O)]·H2O[M=Cu(II)、Cd(II)、Ni(II)、Mn(II)]；[ML1(CH3COO)2(H2O)]·2H2O[M=Zn(II)、Co(II)]；[M(phen)L1(CH3COO)]·CH3COO·3H2O[M=Cu(II)、Cd(II)]。(4) Transition metal complexes with Schiff base ligand (L2) derived from2-hydroxy-1-naphthaldehyde and laminine are synthesized. The possible chemicalcompositions of these complexes are confirmed to be:[ML2(CH3COO)2]·H2O[M=Cu(II)、Cd(II)、Ni(II)、Mn(II)、Zn(II)、Co(II)]；[M(phen)L2(CH3COO)]·CH3COO·H2O[M=Cd(II)、Ni(II)]。(5) Fluorescence spectra of ligands and part of their metal ions complexes aredetected. Meanwhile,the experimental results show that the complex[ZnL2(CH3COO)2]·H2O have good fluorescence activity. Compared with thecorresponding ligand, the excitation and emission peaks of the complex shift to somerange and their fluorescence intensity enhances obviously.(6) The interaction of the [CuL1(CH3COO)2(H2O)]·H2O with CT-DNA has beeninvestigated by UV-Vis spectrometry, fluorescence spectrometry and EB-DNAexperiment. The results demonstrate that the interaction of complex and DNA isintercalation. Moreover, when the ligand has more co-planar, wider flat area andsmaller steric hindrance, its interaction with DNA is more significant, simultaneously,ligand is more favorable to interact with DNA in the way of insertion. (7) The antitumor activities of ligand and some metal ion complexes are studiedby3-[4,5-dimethyltiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT method) inMDA-MB-231breast cancer cells. It is found that [CdL2(CH3COO)2]·2H2O hashigher antitumor activities than other complexes. It is capable of inducing apoptosis inbreast cancer cells in a concentration-and time-dependent fashion.