Molecular Design,Synthesis And Preparation Process Of Hydrogenated Quinoline Schiff Bases Containing Nickel Complexes

Objective:In this thesis,a series of similar Schiff base-like nickel-containing complexes based on 8-arylimino-5,6,7-trihydroquinoline were constructed by combining the structure of Schiff base with 5,6,7-trihydroquinoline as a template and modified by different neighboring substitutions of arylimines,and the effective synthesis process was explored,and the individual products were examined by various characterizations.The potential medicinal value of hydroquinoline Schiff base nickel-containing complexes was investigated from the perspective of network pharmacology by analyzing the molecular structure of the complexes through the detection of single crystals by X-ray diffraction,and exploring the catalytic ability of these nickel（II）complexes in the polymerization of ethylene,expanding the application value of molecular polymerization of ethylene in the production of medical and pharmaceutical packages,and further exploring their potential for a wide range of applications in the pharmaceutical field.Methods:Using a zinc-mediated template method,two substances,2,4-bis（dibenzocycloheptyl）-6-R-aniline and 6,7-dihydro-5H-quinolin-8-one,were subjected to ketamine condensation in glacial acetic acid to finally synthesize five Schiff base ligands,and then the Schiff base ligands were subjected to complexation reactions with（DME）Ni Br₂or Ni Cl₂·6H₂O with the ligands to synthesize ten nickel complexes（Ni1-Ni10）.The synthesized Schiff bases（L1-L5）and nickel complexes（Ni1-Ni10）were characterized and investigated by ¹H NMR,¹³C NMR,¹⁹F NMR,FT-IR,HRMS and elemental analysis.Moreover,the monocrystals of the complexes were studied by X-ray single-crystal diffraction.The molecular structures of the complexes were analyzed,and the properties and characteristics were analyzed.The online prediction of compound action targets was completed at the Swiss Target Prediction Database website using the Swiss Target Prediction database for the complexes Ni1-Ni10.The target sites of all compounds were corrected to official gene names by Uniprot database,and PDB numbers and other related information were found.From Protein Data Bank database,the corresponding receptor proteins were searched for using the queried PDB numbers and screened finally using AUTODOCK vina 1.1.2 and Amber 20software to screen the receptors and ligands by the above method The potential medicinal value of the nickel-containing complexes of hydroquinoline Schiff bases was investigated and speculated from the perspective of network pharmacology.Five different alkylaluminium co-catalysts were used to activate the nickel complexes for the polymerization of ethylene,and the most active aluminoxane and alkylaluminium chloride co-catalysts were selected based on the results of the data.The polymerization data of different structures of the complexes were used to speculate on the effects of the spatial resistance and electronic effects of 6-R,and to further examine the structure and properties of the specified polymer samples to expand the application of this nickel（II）complex in the field of pharmaceutical development.Results:1.Five 8-[2,4-bis（dibenzocycloheptyl）-6-R-arylimino]-5,6,7-trihydroquinoline ligands containing 6-R groups with different spatial and electronic properties were successfully synthesized in high yields and air-stable forms using a zinc chloride-mediated template method,and the C=N absorption peaks of the complexes in FT-IR spectra were shifted to the lower band direction compared to those of the Schiff base ligands,indicating that the ligands The effective coordination between the imine nitrogen atom and the nickel metal center,and the molecules of such Schiff base nickel complexes in solution,easily form a bimetallic center molecular structure bridged by halogen atoms;the distance between Ni-Ni of the nickel bromide complexes is significantly larger than that of the nickel chloride complexes,and the saturated portions of the fused six-membered rings belonging to the N,N-ligands are all due to the sp3 hybridized carbon atoms of C5,C6 and C7 atoms distortion.2.The target simulation pharmacological analysis revealed that Ni1,Ni4,Ni5 and Ni10all contain potentially active targets;Ni1,Ni4 and Ni5 all have two targets,PLG and PLAU,which have the ability to inhibit fibrinogen over-mediated fibrinolysis,resulting in a reduction of inflammatory factors at the site of infection,or may impede further passage of pathogens such as viruses through the tubular wall;Ni4 and Ni5 can both dock with BACE1target protein,which has the ability to inhibit its hydrolysis to produce Aβ,reduce the deposition of protein Aβplaques in the brain,and delay the possibility of entering the onset stage of Alzheimer’s disease;Ni5 can bind to ALOX5 target protein,which can inhibit the production and activity of inflammatory factors through two pathways,which can treat allergic inflammation,and also affect intracellular signaling pathways,thus hindering tumor cell invasion,Ni10 has the potential to inhibit SIRT2 by binding to SIRT2 protein,impeding its inhibition of T-cell metabolism and enhancing the metabolic adaptations and immune effects of lymphocytes,thereby limiting the spread of tumor cells in body.3.After activation with Et Al Cl₂ or MAO,all complexes were active for ethylene polymerization,Ni6/Et Al Cl₂ showed the highest catalytic level in the system,reaching 6.17×10⁶g PE（mol of Ni）^-1 h^-1,and the electron-donating group o-alkyl（R=Me,Et or i Pr）showed higher catalytic properties than those containing o-halide substituents（R=Cl or F）.The complexes exhibited higher catalytic properties than those containing o-halide substituents（R=Cl or F）,and all samples polymerized under the conditions were branched polyethylene waxes and all showed a narrow molecular weight distribution,highlighting the single character of the active species,and microstructural analysis of these waxes by high temperature ¹³C and ¹H NMR spectroscopy showed that they contained mainly short chain branches（>83%methyl branched chains）with chain ends consisting of vinyl and internal vinyl composition.Conclusion:8-Arylimino-5,6,7-trihydroquinoline Schiff bases containing nickel complexes can be synthesized efficiently by zinc-mediated modelling and can be complexed with nickel halides at room temperature to produce stable complexes,and molecular docking simulations have shown that Ni1,Ni4,Ni5 and Ni10 all have potential medicinal uses,with Ni1,Ni4 and Ni5 all having the potential to be used in anti-inflammatory,antiviral Ni1,Ni4 and Ni5 have the possibility of multi-target therapy,Ni10 has the medicinal potential of targeting T lymphocyte proliferation and effect,and Ni5 and Ni10containing fluorine have shown the tendency of anti-tumor effect.The development potential of these nickel（II）complexes in the pharmaceutical field is huge and has a wide range of directions.