Studies On The Synthesis,Structure,Catalysis And Biological Activity Of Rare Earth Metal Amido Complexes Incorporating Imino-Functionalized Indolyl Ligand

Objective:This thesis focused on the synthesis,structure,catalysis and biological activity of rare earth metal amido complexes incorporating imino-functionalized indolyl ligand.To investigate the reactivity of rare earth metal complexes incorporating imino-functionalized indolyl ligand,and to characterize the structure of imino-functionalized indolyl rare earth metal complexes.The catalytic activity of rare earth metal complexes in the guanidination of arylamine and carbodiimide.In vitro cytotoxicity of imino-functionalized indolyl ligand and their rare earth metal complexes were tested by CCK-8 method in human gastric cancer cell line,HGC-27 cell.The study provides a theoretical basis for the design of rare earth metal complex anticancer drug Method:1)All manipulations were carried out under a dry oxygen-free argonatmosphere using standard Schlenk techniques or in a glovebox unless otherwise stated.The reactions of imino-functionalized indolyl ligand 3-(4-Me2N-C6H4CH=N-CH2CH2)C8H5NH(HL)with the rare earth metal amino compounds[(Me3Si)2N]RE(?-Cl)Li(THF)3 at a certain equivalent ratio produced a series of rare earth metal amino complexes incorporating imino-functionalized indolyl ligand.The structures of these complexes were characterized by modern physicochemical characterization methods such as IR,NMR and X-ray single crystal diffraction.2)The imino-functionalized indolyl rare earth metal complexes were used as the catalyst for the guanidation reaction.The reaction of phenyl amine with diisopropylcarbodiimide was used as the reaction model.The catalytic reaction of phenyl amine with diisopropylcarbodiimide was examined under various conditions,such as the catalyst loading,reaction temperature and time,and reaction solvent.Next,different substrates of phenylamines and carbodiimide were tested under the optimized conditions.The results showed that reactions of phenylamines with electron-withdrawing substituted groups afforded much more better results than those of phenylamines with electron-donating groups.And all the guanidine products were characterized by 1H NMR and 13C NMR.3)In vitro cytotoxicity of imino-functionalized indolyl ligand and the rare earth metal complexes incorporating imido-functionalized indolyl ligand were studied by the CCK-8 method in the human gastric cancer cell line,HGC-27 cell.The inhibitory activities of different concentration gradient ligands and various rare earth metal complex solutions were tested to investigate the effect of concentration and rare earth metal ions.Result:1)Imino-functionalized indolyl ligand 3-(4-Me2N-C6H4CH=N-CH2CH2)C8H5NH(HL)and the rare earth metal amino complexes incorporating imino-functionalized indolyl ligand were synthesized successfully.A series of heteronuclear rare earth metal amino complexes {[?1:?-?2-3-(4-Me2N-C6H4CH=N-CH2CH2)C8H5]RE[N(SiMe3)2](?-Cl)Li(THF)}(RE=Y(1a),Sm(1b),Gd(1c),Er(1d),Yb(1e))were obtained by the reaction of 3-(4-Me2N-C6H4CH=N-CH2CH2)C8H5NH(HL)with[(Me3Si)2N]RE(?-Cl)Li(THF)3 at 1:1 ratio.The unexpected binuclear rare earth metal complex {[?-?5:?1):?1:?1-3-[(Me2N)2-C14H9]-(NCH2CH2-C8H5N)2]Gd2[N(SiMe3)2]3}(1f)which the two ligands were closed ring to form the novelty heterocyclic ligand was obtained prolong the reaction time.However,The bis(indolyl)heteronuclear rare earth metal amino complexes {(?1:?1-[?-?2:?1-3-(4-Me2N-C6H4CH=N-CH2CH2)C8H5]Li[?-?2:?1-3-(4-Me2N-C6H4CH=N-CH2CH2)C8H5])RE[N(SiMe3)2]}(RE=Sm(2a),Dy(2b))were generated when the ratio of the reaction of 3-(4-Me2N-C6H4CH=N-CH2CH2)C8H5NH(HL)with[(Me3Si)2N]RE(?-Cl)Li(THF)3 was 2:1.All the kinds of rare earth metal complexes were determined by X-ray single crystal diffraction.The complexes la and lb were also characterized by 1H NMR and�3C NMR.2)The catalytic activities of these rare earth metal amido complexes incorporating imino-fuctionalized indolyl for guanidine reaction of aromatic amines with carbodiimides were explored.The results indicated that these complexes displayed a highly catalytic activity for the guanidine reaction.The guanidine was obtained in 97%yield under solvent-free condition at 100? for 2 h with the employment of low catalyst loadings(1 mol%).The reactions of amines with electron-withdrawing substituted groups afforded much more better results than those of amines with electron-donating groups,and the yield of guanidine products decreased obviously with the increase of substituent hindrance.3)The results of CCK-8 experiments showed that:imino-functionalized indolyl ligand(HL)and the rare earth metal amino complexes both have a biologically active effect on inhibiting the growth of human gastric cancer cell line HGC-27 When the concentrations of the ligand and the rare earth metal complex solutions were both 75 ?mol/L,the inhibition rate of the rare earth metal complexes on the proliferation of human gastric cancer cell line HGC-27 were significantly higher than that of the ligand with statistical significance.The rare earth metal complexes all have the effect of inhibiting the proliferation of human gastric cancer cell line HGC-27 when their solution concentrations were at 25 ?mol/L(or 50 ?mol/L)with statistical significance,and enhanced with the increase of the concentration of the complexes,and it appears dose-dependentConclusion:A series novel of rare earth metal amino complexes incorporating imino-functionalized indolyl ligand have been synthesized and characterized by nuclear magnetic resonance,X-ray single crystal diffraction,infrared spectrum,and elemental analysis.All complexes showed a high activity toward the reaction of aromatic amines and carbodiimides producing guanidines.The guanidine was obtained in high yield under solvent-free condition at 100? for short time with the employment of low catalyst loading.In vitro activity cytotoxicity of imino-functionalized indolyl ligand and their rare earth metal complexes were tested by CCK-8 method in human gastric cancer cell line,HGC-27 cell The results indicated that the inhibitory activity of the rare earth metal complexes were better than the ligand.The study provides a theoretical basis for the design of anticancer drug precursors and drug structures.