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Palladium(II) complexes of tridentate bis(benzazole) ligands: Structural, substitution kinetics, DNA interactions and cytotoxicity studies.

Omondi, RO, Bellam, R, Ojwach, SO, Jaganyi, D and Fatokun, AA (2020) Palladium(II) complexes of tridentate bis(benzazole) ligands: Structural, substitution kinetics, DNA interactions and cytotoxicity studies. Journal of Inorganic Biochemistry, 210. ISSN 0162-0134

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Omondi et al (2020) J Inorg Biochem 210, 111156.pdf - Accepted Version
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Abstract

Reactions of 2,6-bis(benzimidazol-2-yl)pyridine (L1), 2,6-bis(benzoxazol-2-yl)pyridine (L2), and 2,6-bis(benzothiazol-2-yl)pyridine (L3) with [Pd(NCMe)2Cl2] in the presence of NaBF4 afforded the corresponding Pd(II) complexes, [Pd(L1)Cl]BF4, PdL1; [Pd(L2)Cl]BF4, PdL2; [Pd(L3)Cl]BF4, PdL3; respectively, while reaction of bis[(1H-benzimidazol-2-yl)methyl]amine (L4) with [Pd(NCMe)2Cl2] afforded complex [Pd(L4)Cl]Cl, PdL4. Characterisation of the complexes was accomplished using NMR, IR, MS, elemental analyses and single crystal X-ray crystallography. Ligand substitution kinetics of these complexes by biological nucleophiles thiourea (Tu), L-methionine (L-Met) and guanosine 5'-diphosphate disodium salt (5-GMP) were examined under pseudo-first order conditions. The reactivity of the complexes decreased in the order: PdL1 > PdL2 > PdL3 > PdL4, ascribed to electronic effects. Density functional theory (DFT) supported this trend. Studies of interaction of the Pd(II) complexes with calf thymus DNA (CT-DNA) revealed strong binding affinities via intercalative binding mode. Molecular docking studies established associative non-covalent interactions between the Pd complexes and DNA. The in vitro cytotoxic activities of PdL1-PdL4 were assessed in cancer cell lines HeLa and MRC5-SV2 and a normal cell line MRC-5, using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. PdL1 exhibited cytotoxic potency and selectivity against HeLa cell that was comparable to cisplatin's. Complex PdL1, unlike cisplatin, did not significantly induce caspase-dependent apoptosis.

Item Type: Article
Uncontrolled Keywords: 0302 Inorganic Chemistry, 0307 Theoretical and Computational Chemistry, 0399 Other Chemical Sciences
Subjects: Q Science > QD Chemistry
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Elsevier
Related URLs:
Date Deposited: 11 Aug 2020 10:09
Last Modified: 11 Aug 2020 10:15
DOI or Identification number: 10.1016/j.jinorgbio.2020.111156
URI: https://researchonline.ljmu.ac.uk/id/eprint/13474

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