- Title
- Synthesis, characterisation and antitumour activities of lanthanide complexes with hydrazones and carboxylic acid ligands
- Creator
- Madanhire, Tatenda
- Subject
- Organic acids
- Date Issued
- 2020
- Date
- 2020
- Type
- Thesis
- Type
- Doctoral
- Type
- PhD
- Identifier
- http://hdl.handle.net/10948/48456
- Identifier
- vital:40878
- Description
- The tridentate hydrazone ligands, (E)-N'-(2-hydroxybenzylidene)benzohydrazide (H2phen) and (E)-N'-(2-hydroxybenzylidene)nicotinohydrazide (H2Nic), were synthesised and complexed to Ln(III) acetates. The centrosymmetric, acetato-bridged dinuclear coordination compounds with the formulae, [La2(Hphen)2(OAc)4(H2O)2]·DMF·H2O (1), [Ln2(HNic)2(OAc)4(H2O)2]·DMF·H2O (Ln = La (2) and Nd (3)) and [Ln2(HNic)2(OAc)4(H2O)2]·DMF (Ln = Er (4) and Yb (5)) were isolated and characterised by elemental analyses, IR spectroscopy, UV-Vis spectroscopy, X-ray diffraction studies and SHAPE 2.1. The nine-coordinate complexes 1–3 crystallise in the triclinic space group P-1, with the metal centres having the distorted spherical capped square antiprism geometry (C4v), while the eight-coordinate Er(III) and Yb(III) complexes (monoclinic system, space group P21/c) display the geometry of distorted triangular dodecahedron (D2d). Geometry optimisation of the monoanionic forms of the hydrazone ligands (Hphen– and HNic– ) were performed using Density Functional Theory (DFT) with Becke’s three parameter hybrid method and correlation functional of Lee, Yang and Parr (B3LYP) with augcc-pVTZ basis set. Natural population analysis (NPA) and molecular electrostatic potential (MEP) maps indicated that the most preferred sites for electrophilic attack in the anionic ligands are the phenolate and carbonyl oxygens, and the azomethine nitrogens. The evaluation of the cytotoxic activity of the compounds on breast cancer (MCF-7), the endometrial carcinoma (HEC-1A) and the human monocytic (THP-1) cell lines using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay revealed that the hydrazone ligands and complexes 1–4 are partially cytotoxic against MCF-7 cells, while the Schiff bases and complexes 3–5 significantly inhibit cell growth in HEC-1A cells. The complexation reactions of Ce(III), Nd(III), Gd(III) and Er(III) with the chelating/ bridging monoanionic ligand N-(2,6-dimethylphenyl)oxamate (Hpma– ) in basic media were performed in view of the potential applications of oxamate derivatives as cytotoxic agents. The coordination compounds were characterised by different Abstract T. Madanhire Nelson Mandela University xxvi physico-chemical techniques: elemental analysis, conductivity measurements, IR, 1 H NMR and UV-Vis-NIR spectroscopy. The anionic Hpma– was obtained through conversion of the proligand ethyl (2,6-dimethylphenylcarbamoyl)formate (Hdmp). The reactions afforded lanthanide(III)–oxamate coordination polymers of formulae: {[Ln(Hpma)3(MeOH)(H2O)]∙2MeOH}n (Ln = Ce (1) and Nd (2)), {[Gd2(Hpma)6(MeOH)4]∙6MeOH}n (3), {[Er2(Hpma)6(MeOH)(H2O)3]∙2MeOH}n (4) and [Ln2Na2(Hpma)8(EtOH)(H2O)6]n (Ln = Nd (5) and Gd (6)). The polymeric complexes feature Ln-Hpma moieties bridged by μ2-η 1 :η 1 :η 1 Hpma– , giving onedimensional zig-zag chains of the –Ln–O–C–O–Ln– type. Atomic charge analysis and the MEP map of the Hpma– moiety done using the DFT/B3LYP method were found to be consistent with the chelating and bridging modes of the anionic ligand through all the oxygen atoms. The evaluation of the cytotoxic activities of the metal salts, the proligand and the novel lanthanide complexes on MCF-7, HEC-1A and THP-1 cell lines revealed that only the rare-earth metal salts [Ce(NO3)3∙6H2O] and [Nd(NO3)3∙6H2O] showed modest cytotoxicity against MCF-7 and HEC-1A cells, respectively.
- Format
- XXviii, 233 leaves
- Format
- Publisher
- Nelson Mandela University
- Publisher
- Faculty of Science
- Language
- English
- Rights
- Nelson Mandela University
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NMU School of BioMolecular and Chemical Sciences
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