Electronic and ring size effects of N-heterocyclic carbenes on the kinetics of ligand substitution reactions and DNA/protein interactions of their palladium(II) complexes

The synthesis, substitution kinetics and DNA/BSA interactions of four cationic Pd(II) complexes [Pd(1)Cl]BF(4) (Pd1), [Pd(2)Cl]BF(4) (Pd2), [Pd(3)Cl]BF(4) (Pd3) and [Pd(4)Cl]BF(4) (Pd4), derived from the reaction of [PdCl(2)(NCCH(3))(2)] with ligands 2,6-bis(3-methylimidazolium-1-yl)pyridine dibromide (1), 2,6-bis(3-ethylimidazolium-1-yl)pyridine dibromide (2), 2,6-bis(1-methylimidazole-2-thione)pyridine (3), and 2,6-bis(1-ethylimidazole-2-thione)pyridine (4), respectively are reported. The complexes were characterised by various spectroscopic techniques and single crystal X-ray diffraction for compound Pd2. Kinetic reactivity of the complexes with the biologically relevant nucleophiles thiourea (Tu), L-methionine (L-Met) and guanosine 5′-monophosphate sodium salt (5’-GMP) was in the order: Pd1 > Pd2 > Pd3 > Pd4, which was largely dependent on the electronic and ring size of the chelate ligands, consistent with Density functional theory (DFT) simulations. The interactions of the complexes with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) binding titrations showed strong binding. Both the experimental and in silico data reveal CT-DNA intercalative binding mode. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10534-023-00507-8.