الفهرس 
AcknowledgmentOnly 14 pages are availabe for public view
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Abstract
Imines are condensation products of primary amines and carbonyl (ketone or aldehyde) compounds. They were discovered by a German chemist, Nobel Prize winner, Hugo Schiff in 1864. Imine ligands are excellent coordinating ligands. Their importance is due to from stable complexes easily with a variety of metal ions. During the past three decades, considerable attention has been paid to the chemistry of the complexes of the imine ligands containing nitrogen and other donors. This attributed to their stability, biological activity and potential applications in many fields making the behavior of imine complexes with transition metals a worthy research topic. The coordination chemistry of imine ligand is also of considerable interest due to interesting applications in medicine, material science and catalysis. Furthermore, transition metal complexes of imines are one of the most adaptable and thoroughly studied systems. Thus, the scope of the present thesis is to prepare two new bi - dentate hydrazone imine ligands containing 2,4-dihydroxybenzaldhyde and 2-hydroxy-1-napthaldehyde (carbonyl group) with the result of reaction between benzophenone and hydrazine hydrate . Use the prepared hydrazone imine ligands to synthesize some novel complexes of Cu(II), Mn(II), Fe(III) and Cr(III). The prepared ligands which used in the study: DPHB: (Benzhydrylidene-hydrazonomethyl)-benzene-1, 3-diol. DPHN: (Benzhydrylidene-hydrazonomethyl)-naphthalen-2-ol. Summary
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The study involves characterization of the prepared hydrazone imine ligands and their complexes using NMR spectra, elemental analysis, electronic spectra, TGA, magnetic susceptibility and molar conductance measurements. The structure of imine ligands are authenticated by their melting points, electronic, infrared spectra, nuclear magnetic resonance and elemental analysis . The study of thermal stability of the prepared imine complexes using TGA technique. Determination of kinetic and thermodynamic parameters of the prepared imine complexes using Coats–Redfern equation. Assessment of antimicrobial and anticancer activity of the prepared imine ligands and their complexes. Interaction of the prepared imine complexes with CT-DNA was checked by using Uv/ Visible spectra, viscosity measurements and gel electrophoresis. This thesis contains four main chapters. In what follows a brief description of each chapter included in the present thesis. Chapter I: ” Introduction” This chapter presents a literature survey of the previous work out on: Giving background about imine ligands. Also, it shows a literature survey on biological activity of imines and their complexes and a literature survey on preparation and characterization of imine complexes. Moreover, it offers a literature survey on DNA interaction with complexes and anticancer activity.
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Chapter II: ” Experimental” The second chapter describes a concise survey of materials and reagents used in the investigation. The techniques and apparatus used are also outlined. The experimental details for the preparation of hydrazone imine ligands and their complexes under investigation were mentioned. Moreover, this chapter involves the instruments and methods used to characterize the isolated imine ligands and their complexes. Moreover, it contains method for DFT calculations used for confirmation the structure of the prepared ligands and their complexes. Also, it includes the detailed procedures for biological studies, DNA interaction with the investigated complexes and molecular docking studies. Chapter III: ” Results” The third chapter concerned with the results obtained: Structural elucidation of hydrazone imine ligands and their complexes has been made on the basis of 1H NMR, 13C NMR, melting point or decomposition temperatures, micro-analytical, IR spectral analyses, UV-Vis spectra, magnetic measurements, conductivity measurements, thermogravimetric analyses (TGA), kinetic-thermodynamic parameters determination and spectrophotometric determination stoichiometry. Optimization geometry of complexes of hydrazone ligands were carried out by density functional theory (DFT) calculations. Antimicrobial activity of the prepared imine ligands and their complexes against different types of microorganism; bacteria (Escherichia coli , Serratia Marcescence as Gram-negative bacteria and Microccus Luteus as Gram-positive bacteria) and
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three fungal cultures (Aspergillus flavus, Getrichm candidum and Fusarium oxysporum ) were evaluated at different concentrations (10 and 25 mg/ ml). Moreover, activity index and minimum inhibitory concentrations for the studied compounds were evaluated. Investigation of interaction of the prepared imine complexes with CT-DNA by different techniques such as electronic spectra, viscosity and gel electrophoresis. Anticancer activity for the prepared imine ligands and their complexes against HCT-116 cancer cells, MCF-7 cancer cells and HepG 2 cancer cells. Docking study of the investigated hydrazone ligands and their complexes was performed to get a first insight of the interaction in the active site of the protein enzyme of the bacteria and fungi receptors Chapter IV: ” Discussion” This chapter is concerned with the discussion of the results set out in the previous chapter. In the light of the results obtained from using characterization techniques. o characterization of hydrazone imine ligands and their complexes Correlation of all obtained data suggested that DPHB and DPHN hydrazone imine ligands behave as dibasic bi-dentate NO ligand and coordinate with metal ions in octahedral geometry in case of DPHBCr, DPHBCu,
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DPHBFe, DPHNMn and DPHNFe complexes and in square planner geometry for DPHNCu complex. All these complexes are non-electrolyte in nature according to the conductivity measurements. Magnetic measurements of all the prepared hydrazone imine complexes referred as paramagnetic complexes. Formation constants (Kf) values indicate the high stability of the prepared complexes decrease in the following order: DPHNMn > DPHBFe > DPHBCr > DPHNCu > DPHNFe > DPHBCu complex. The thermal behaviour of metal chelates indicated that hydrated water molecules of hydration lose in the first step followed immediately by decomposition of the coordinated water molecules and ligand molecules in the subsequent steps. The Kinetic parameters refer to the high values of the activation energies which represent the thermal stability of the complexes at the studied conditions and the decomposition process is non-spontaneous and unfavourable. The pH- profile (absorbance vs. pH) showed typically dissociation curves and a wide stability pH range (” ” " ~ " ” ” 4 - 11) for the prepared complexes. This means that the formation of the complex greatly stabilizes the prepared hydrazone imine ligands. Consequently, the suitable pH range for the various fields of the tested complexes is from pH =4 to pH = 10.
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o Applications of the prepared hydrazone ligands and their complexes. The antimicrobial screening results offered a marked improvement in activity on coordination with the metal ions against bacteria and fungi. This improvement in the activity can be rationalized to the basis of chelating which is serious in identifying the mechanism of transamination and resamination reaction in biological system. Electronic absorption, viscosity measurements and agarose gel electrophoresis studies have revealed that the prepared complexes are avid binders of the calf thymus (CT- DNA). Binding constant values is more comparable with typical known intercalators (EB-DNA, 3.3 × 105 L mol−1). It can be concluded that there is great strength binding of the prepared complexes with DNA. The investigated complexes could connect with DNA via an intercalative, replacement and electrostatic modes with the sequence: DHPNFe > DPHBCu > DHPNMn > DPHBCr > DHPNCu > DPHBFe complex. The results revealed that the difference of the metal might lead to obvious difference of DNA binding abilities of the complexes. These results promise that theses complexes can be used in cancer therapy. Anticancer activity results indicated that all tested complexes demonstrated potent cytotoxicity against HCT-116 cancer cells, MCF-7 cancer cells and HepG 2 cancer cells compared with their prepared imine ligands.
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The docking results were imported into the workspace and the pose organizer was used for exploring the returned poses for each ligand, in addition to inspecting the difference in the docking score for each enantiomeric pair. In addition to examining the docking score, each pose was visually inspected and compared to the experimentally determined binding mode of the natural ligands. Key protein-ligand contacts and interactions were examined. Protein–ligand interactions were analyzed using DS viewer and MVD. The docked compounds were scored and ranked using the “re-rank score”. Finally, the thesis was finished with a number of references, which helped the explanation of the results.