Role of π-conjugation on the coordination behaviour, substitution kinetics, DNA/BSA interactions, and in vitro cytotoxicity of carboxamide palladium(ii) complexes

Abstract

Treatments of N-(pyridin-2-ylmethyl)pyrazine-2-carboxamide (L₁), N-(quinolin-8-yl)pyrazine-2-carboxamide (L₂), N-(quinolin-8-yl)picolinamide (L₃) and N-(quinolin-8-yl)quinoline-2-carboxamide (L₄) with [PdCl₂(NCMe)]₂ afforded the corresponding Pd(II) complexes, [Pd(L₁)Cl] (PdL₁); [Pd(L₂)Cl] (PdL₂); [Pd(L₃)Cl] (PdL₃); and [Pd(L₄)Cl] (PdL₄) in moderate yields. Structural characterisation of the compounds was achieved by NMR and FT-IR spectroscopies, elemental analyses and single crystal X-ray crystallography. The solid-state structures of complexes PdL₂–PdL₄ established the presence of one tridentate carboxamide and Cl ligands around the Pd(II) coordination sphere, to give distorted square planar complexes. Electrochemical investigations of PdL₁–PdL₄ showed irreversible one-electron oxidation reactions. Kinetics reactivity of the complexes towards bio-molecules, thiourea (Tu), L-methionine (L-Met) and guanosine 5′-diphosphate disodium salt (5′-GMP) decreased in the order: PdL₁ > PdL₂ > PdL₃ > PdL₄, in tandem with the density functional theory (DFT) data. The complexes bind favourably to calf thymus (CT-DNA), and bovine serum albumin (BSA), and the order of their interactions agrees with the substitution kinetics trends. The in vitro cytotoxic activities of PdL₁–PdL₄ were examined in cancer cell lines A549, PC-3, HT-29, Caco-2, and HeLa, and a normal cell line, KMST-6. Overall, PdL₁ and PdL₃ displayed potent cytotoxic effects on A549, PC-3 HT-29 and Caco-2 comparable to cisplatin. All the investigated complexes exhibited lower toxicity on normal cells than cisplatin.