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.

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The coordination chemistry of four carboxamide palladium(ii) complexes, their substitution kinetics, interactions with DNA/BSA and cytotoxicity against a series of cancer cells has been investigated.

Highlights Ruthenium(III) complexes were successfully synthesised.  The substitution of the coordinated chloro ligands happened simultaneously.  Density functional theoretical calculations supports substitution kinetic results.  Complexes demonstrate low antineoplastic properties against Hela cancer cells.  Molecular docking of the compounds demonstrate good affinity for DNA molecule.

The pincer complexes, [Pd(L 1 )Cl]BF 4 (PdL 1 ), [Pd(L 2 )Cl]BF 4 (PdL 2 ), [Pd(L 3 )Cl]BF 4 (PdL 3 ), [Pd(L 4 )Cl]BF 4 (PdL 4 ) were prepared by reacting the corresponding ligands, 2,6-bis[(1H-pyrazol-1-yl)methyl]pyridine (L 1 ), bis[2-(1H-pyrazol-1-yl)ethyl] amine (L 2 ), bis[2-(1H-pyrazol-1-yl)ethyl]ether (L 3 ), and bis[2-(1H-prazol-1-yl)ethyl]sulphide (L 4 ) with [PdCl 2 (NCMe)] 2 in the presence NaBF 4 . The solid-state structures of complexes PdL 1 -PdL 4 confirmed a tridentate coordination mode,with one chloro ligand completing the coordination sphere to afford square-planar complexes. Chemical behaviour of the complexes in solution confirms their stability in both aqueous and DMSO stock media. The electrochemical properties of the compounds showed irreversible two-electron reduction process. Kinetic reactivity of Pd complexes with the biological nucleophiles viz, thiourea (Tu), L-methionine (L-Met) and guanosine 5′-diphosphate disodium salt (5'-GMP) followed the order: PdL 2 < PdL 3 < PdL 4 , and PdL 2 < PdL 1 . The kinetic reactivity is subject to the electronic effects of the spectator ligand(s), and the trend was supported by the DFT computed results. The palladium complexes PdL 1 -PdL 4 bind to calf thymus (CT-DNA) via intercalation mode. In addition, the bovine serum albumin (BSA) showed good binding affinity to the complexes. The mode of quenching mechanism of the intrinsic fluorescence of CT-DNA and BSA by the complexes was found to be static. The order of interactions of the complexes with DNA and BSA was in tandem with the rate of substitution kinetics. The complexes, however, displayed relatively low cytotoxicity (IC 50 > 100 µM) when tested against the human cervical adenocarcinoma (HeLa) cell line and the transformed human lung fibroblast cell line (MRC-5 SV2).