Synthesis, characterisation and antitumour activities of lanthanide complexes with hydrazones and carboxylic acid ligands
- Authors: Madanhire, Tatenda
- Date: 2020
- Subjects: Organic acids
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/48456 , 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.
- Full Text:
- Date Issued: 2020
- Authors: Madanhire, Tatenda
- Date: 2020
- Subjects: Organic acids
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/48456 , 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.
- Full Text:
- Date Issued: 2020
Synthesis and characterisation of lanthanide complexes with nitrogen- and oxygen-donor ligands
- Authors: Madanhire, Tatenda
- Date: 2016
- Subjects: Rare earth metals
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/13127 , vital:27154
- Description: The reactions of Ln(NO3)3∙6H2O (Ln = Pr, Nd or Er) with the potentially tridentate O,N,O chelating ligand 2,6-pyridinedimethanol (H2pydm) were investigated, and complexes with the formula, [Ln(H2pydm)2(NO3)2](NO3) (Ln = Pr or Nd) and [Er(H2pydm)3](NO3)3 were isolated. The ten-coordinate Pr(III) and Nd(III) compounds crystallise in the triclinic space group P-1 while the nine-coordinate Er(III) complex crystallises in the monoclinic system (P21/n). The reaction of PrCl3∙6H2O with H2pydm yielded the compound, [Pr(H2pydm)3](Cl)3, that crystallises in the monoclinic system, space group P21/c with α = 90, β = 98.680(1) and γ = 90°. The nine-coordinate Pr(III) ion is bound to three H2pydm ligands, with bond distances Pr-O 2.455(2)-2.478(2) Å and Pr-N 2.6355(19)-2.64(2) Å. X-ray crystal structures of all the H2pydm complexes reveal that the ligand coordinates tridentately, via the pyridyl nitrogen atom and the two hydroxyl oxygen atoms. The electronic absorption spectra of complexes show 4f-4f transitions. Rare-earth complexes, [Ln(H2L1)2(NO3)3] [Ln = Gd, Ho or Nd], were also prepared from a Schiff base. The X-ray single-crystal diffraction studies and SHAPE analyses of the Gd(III) and Ho(III) complexes shows that the complexes are ten-coordinate and exhibit distorted tetradecahedron geometries. With proton migration occurring from the phenol group to the imine function, complexation of the lanthanides to the ligand gives the ligand a zwitterionic phenoxo-iminium form. A phenolate oxygen-bridged dinuclear complex, [Ce2(H2L1)(ovan)3(NO3)3], has been obtained by reacting Ce(NO3)3∙6H2O with an o-vanillin derived Schiff base ligand, 2-((E)-(1-hydroxy-2-methylpropan-2-ylimino)methyl)-6-methoxyphenol (H2L1). Hydrolysis of the Schiff base occurred to yield o-vanillin, which bridged two cerium atoms with the Ce∙∙∙Ce distance equal to 3.823 Å. The Ce(III) ions are both tencoordinate, but have different coordination environments, showing tetradecahedron and staggered dodecahedron geometries, respectively. The reaction of salicylaldehyde-N(4)-diethylthiosemicarbazone (H2L2) in the presence of hydrated Ln(III) nitrates led to the isolation of two novel compounds: (E)-2[(ortho-hydroxy)benzylidene]-2-(thiomethyl)-thionohydrazide (1) and bis[2,3-diaza4-(2-hydroxyphenyl)-1-thiomethyl-buta-1,3-diene]disulfide. The latter is a dimer of the former. For this asymmetric Schiff base, 1 and the symmetric disulfide, classical hydrogen bonds of the O–H∙∙∙N as well as N–H∙∙∙S (for 1) type are apparent next to C–H∙∙∙O contacts. 4-(4-Bromophenyl)-1-(propan-2-ylidene)thiosemicarbazide was also prepared upon reacting 4-(4-bromophenyl)-3-thiosemicarbazide with acetone in the presence of ethanol and La(NO3)3∙6H2O. The C=S bond length was found to be 1.6686(16) Å which is in good agreement with other thioketones whose metrical parameters have been deposited with the Cambridge Structural Database. Classical hydrogen bonds of the N–H∙∙∙N and the N–H∙∙∙Br type are observed next to C–H∙∙∙S contacts. All synthesised compounds were characterised by microanalyses, single-crystal X-ray diffraction (except for [Nd(H2L1)2(NO3)3]), 1H NMR and IR spectroscopy.
- Full Text:
- Date Issued: 2016
- Authors: Madanhire, Tatenda
- Date: 2016
- Subjects: Rare earth metals
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/13127 , vital:27154
- Description: The reactions of Ln(NO3)3∙6H2O (Ln = Pr, Nd or Er) with the potentially tridentate O,N,O chelating ligand 2,6-pyridinedimethanol (H2pydm) were investigated, and complexes with the formula, [Ln(H2pydm)2(NO3)2](NO3) (Ln = Pr or Nd) and [Er(H2pydm)3](NO3)3 were isolated. The ten-coordinate Pr(III) and Nd(III) compounds crystallise in the triclinic space group P-1 while the nine-coordinate Er(III) complex crystallises in the monoclinic system (P21/n). The reaction of PrCl3∙6H2O with H2pydm yielded the compound, [Pr(H2pydm)3](Cl)3, that crystallises in the monoclinic system, space group P21/c with α = 90, β = 98.680(1) and γ = 90°. The nine-coordinate Pr(III) ion is bound to three H2pydm ligands, with bond distances Pr-O 2.455(2)-2.478(2) Å and Pr-N 2.6355(19)-2.64(2) Å. X-ray crystal structures of all the H2pydm complexes reveal that the ligand coordinates tridentately, via the pyridyl nitrogen atom and the two hydroxyl oxygen atoms. The electronic absorption spectra of complexes show 4f-4f transitions. Rare-earth complexes, [Ln(H2L1)2(NO3)3] [Ln = Gd, Ho or Nd], were also prepared from a Schiff base. The X-ray single-crystal diffraction studies and SHAPE analyses of the Gd(III) and Ho(III) complexes shows that the complexes are ten-coordinate and exhibit distorted tetradecahedron geometries. With proton migration occurring from the phenol group to the imine function, complexation of the lanthanides to the ligand gives the ligand a zwitterionic phenoxo-iminium form. A phenolate oxygen-bridged dinuclear complex, [Ce2(H2L1)(ovan)3(NO3)3], has been obtained by reacting Ce(NO3)3∙6H2O with an o-vanillin derived Schiff base ligand, 2-((E)-(1-hydroxy-2-methylpropan-2-ylimino)methyl)-6-methoxyphenol (H2L1). Hydrolysis of the Schiff base occurred to yield o-vanillin, which bridged two cerium atoms with the Ce∙∙∙Ce distance equal to 3.823 Å. The Ce(III) ions are both tencoordinate, but have different coordination environments, showing tetradecahedron and staggered dodecahedron geometries, respectively. The reaction of salicylaldehyde-N(4)-diethylthiosemicarbazone (H2L2) in the presence of hydrated Ln(III) nitrates led to the isolation of two novel compounds: (E)-2[(ortho-hydroxy)benzylidene]-2-(thiomethyl)-thionohydrazide (1) and bis[2,3-diaza4-(2-hydroxyphenyl)-1-thiomethyl-buta-1,3-diene]disulfide. The latter is a dimer of the former. For this asymmetric Schiff base, 1 and the symmetric disulfide, classical hydrogen bonds of the O–H∙∙∙N as well as N–H∙∙∙S (for 1) type are apparent next to C–H∙∙∙O contacts. 4-(4-Bromophenyl)-1-(propan-2-ylidene)thiosemicarbazide was also prepared upon reacting 4-(4-bromophenyl)-3-thiosemicarbazide with acetone in the presence of ethanol and La(NO3)3∙6H2O. The C=S bond length was found to be 1.6686(16) Å which is in good agreement with other thioketones whose metrical parameters have been deposited with the Cambridge Structural Database. Classical hydrogen bonds of the N–H∙∙∙N and the N–H∙∙∙Br type are observed next to C–H∙∙∙S contacts. All synthesised compounds were characterised by microanalyses, single-crystal X-ray diffraction (except for [Nd(H2L1)2(NO3)3]), 1H NMR and IR spectroscopy.
- Full Text:
- Date Issued: 2016
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