Synthesis, structure and molecular docking studies of dicopper(ii) complexes bridged by N-phenolato-N′-[2-(dimethylamino)ethyl]oxamide: the influence of terminal ligands on cytotoxicity and reactivity towards DNA and protein BSA

Abstract

Two dicopper(II) complexes bridged by N-phenolato-N′-[2-(dimethylamino)ethyl]oxamide (H₃pdmaeox) and end-capped with 2,2′-diamino-4,4′-bithiazole (dabt) and 2,2′-bipyridine (bpy), respectively, namely [Cu₂(pdmaeox)Cl(CH₃OH)(dabt)]·CH₃OH (1) and [Cu₂(pdmaeox)(bpy)(H₂O)]-(pic)·H₂O (2) (where pic⁻ denotes the picrate anion) have been synthesized. Complex 1 was characterized by elemental analysis, molar conductivity measurements, IR and electronic spectral studies, and single-crystal X-ray diffraction. The crystal structure analyses reveal that the dissymmetric unit of complex 1 contains a neutral dicopper(II) complex moiety [Cu₂(pdmaeox)Cl-(CH₃OH)(dabt)], in which the cis-pdmaeox³⁻ ligand bridges two copper(II) ions with the separation of 5.2238(19) Å. Through hydrogen bonding interactions, complex 1 molecules are assembled into 3D supramolecular structures. The structure and DNA-binding activities of complex 2 have been reported in our previous paper. However, its other properties were not studied. In order to gain some insight into the structure–activity relationship, the reactivities towards DNA and protein of the two dicopper(II) complexes are studied both theoretically and experimentally. The DNA docking study suggests that all the two dicopper(II) complexes can interact with DNA through the minor groove, and the binding affinity follows the order of 1 > 2, which is further validated by spectral titration, electrochemical techniques, and viscosity measurements. Bovine serum albumin (BSA) binding activity studies revealed that the two dicopper(II) complexes can strongly quench the intrinsic fluorescence of BSA through a static quenching mechanism with the ratio of the dicopper(II) complex to BSA being 1 : 1, and the most possible binding site is in the proximity of Trp134. The in vitro anticancer activities indicate that the two dicopper(II) complexes are active against the selected tumor cell lines, and the order of in vitro anticancer activities is consistent with the DNA-binding affinities. The influence of structural variation of the terminal ligands in the dicopper(II) complexes on DNA-binding modes and anticancer activities is preliminarily discussed.