Study On The Interactions Of Biological Macromolecules With Some Natural Compounds, Quinolinecarbaldyhyde Schiffbase Ligands And Their Rare-earth Metal Complexes

This dissertation comprises of three chapters.The molecular biological foundation of DNA and Ig(Immunoglobulin),the research technology and methods of DNA and protein with drugs as well as the research and advance in quinoline derivatives with biological activities are summarized in chapter 1.In the chapter 2,four new Schiff-base ligands,8-hydroxyquinoline-2-carbaldehyde-(benzoyl)hydrazone,8-hydroxyquinoline-2-carbaldehyde-(2'-hydroxybenzoyl) hydrazone,8-hydroxyquinoline-2-carbaldehyde-(4'-hydroxybenzoyl)hydrazone and 8-hydroxyquinoline-2-carbaldehyde-(isonicotinyl)hydrazone,are synthesized,respectively,from 8-hydroxy-quinoline-2-carbaldehyde and four aroylhydrazides.Moreover,their 40 lanthanide complexes are synthesized.The structrues of these ligands and rare-earth metal complexes are determined by FT-IR spectra,¹H NMR,ESI-Trap/Mass,Elemental analyses,Molar conductance and X-crystallogrphy.Experimental results indicate that all the powder metal complexes are of[LnL^1-4(NO₃)(OH₂)₂]₂ from La(â…¢) to Er(â…¢) complexes while their crystals have the framework of[LnL^1-4(NO₃)(DMF)₂]₂,where one H₂O/DMF molecule is binding orthogonally to the ligand-plane from one side to the metal ion,while another H₂O/DMF and a nitrate anion(bidentate) are binding from the other.However, powder Yb(â…¢) complexes and crystals have the frameworks of[YbL^1-4(NO₃)(OH₂)]₂ and[YbL^1-4(NO₃)(DMF)]₂,respectively,where one H₂O/DMF molecule is binding orthogonally to the ligand-plane from one side to the metal ion,while a nitrate anion (bidentate) are binding from the other.For all these metal complexes,every ligand acts as a dibasic tetradentate ligand,binding to metal ion through the phenolate oxygen atom,nitrogen atom of quinolinato unit,C=N group,and ^-O-C=N- group (enolized and deprotonated from O=C-NH-) of the aroylhydrazine side chain. Dimerization of the monomeric unit occurs through the phenolate oxygen atoms leading to a central planar four-membered(LnO)₂ ring. Studies on the interaction of ligands and metal complexes and Calf thymus DNA (CT-DNA) indicate that all the investigated compounds can bind to CT-DNA through intercalative modes,but the bindings of metal complexes to CT-DNA are more efficient than those of ligands.Fluorescent trace methods by ethidium bromide(EtBr) indicate that all the investigated compounds may have potential anti-tumor activities but the anti-tumor activities metal complexes may be better than those of ligands, however,their pharmacodynamical,pharmacological and toxicological properties should be further studied in vivo.Anti-oxidation experimental results indicate that all the investigated compounds have strong anti-oxidation activities including scavenging hydroxyl radicals and superoxide radicals.However,ligands and metal complexes containing active phenolic hydroxyl groups show stronger scavenging effects for hydroxyl radicals,and metal complexes containing N-heteroaromatic substituents show stronger scavenging effects for superoxide radicals.This indicates that there are different mechamisms between scavenging hydroxyl radicals and superoxide radicals. Adding a reactive entity endowed with oxidative properties should improve the efficiency of inhibition of the formation of a DNA/TBP complex or topoisomerases.In the chapter 3,the interactions of intravenous immunoglobulin(IVIG) with four plant active components including Taxol,Curcumin,Kaempferol and Quercetin are investigated through fluorescence quening,FT-IR spectra,CD(circular dichroism) spectra,TEM(transmission electron microscopy),molecular modeling and other experimental methods,etc.The experimental results indicate that a partial unfolding of the protein structure take place after addition of every drug,but the typicalβstructural conformation of IVIG is retentive,that is,the biological and immunological functions of IVIG may retentive.The interactions of drugs and IVIG are all non-specific and weak,so IVIG can be used as transfer protein for these drugs in vivo.In addition,the interaction of Taxol and IVIG can inhibit Taxol from crystallizing in aqueous solution when the molar concentration ratio of Taxol to IVIG does not exceed 15:1.Moreover,Quercetin containing 3'-OH has higher binding constant than Kaempferol,and may be more efficient agent to stable the secondary structure and inhibit the random of protein in comparison with Kaempferol.However,the interactions of these drugs and IVIG are slightly weaker than their binding to human serum albumin(HSA).These studies will provide fundamental data for clinicians who may construct new protocols for patients by using the high-safety profile of drug-protein conjugates and provide some references in drug research.Additionally,these studies have established a nearly integrated experimental method,which will be a guide and meaningful for the subsequent interactions of drugs and proteins,especially for metal complex drugs.