Dinuclear Cu(II) and Ni(II) complexes with bis(pyridylimine) ligands: Comparative analysis of the reactivity of ligated imine and an in-depth investigation of the DNA/complex interactions

The reactions of hydrated Cu(ClO₄)₂ and NiCl₂ with substituted bis(pyridylimine) ligands ((PyR)₂en, where R = Me or OMe on the 6-position of the pyridine) have been carried out and the product characterization for four new dinuclear complexes are reported, including single crystal XRD as well as UV/Vis and IR spectroscopic analyses supported by DFT calculations. The copper(II) complexes of both ligands resulted in the formation of analogous species, namely [(Cu((PyMe)enH₂))₂(PyMe)₂en](ClO₄)₄ (1) and [(Cu((PyOMe)enH₂))₂(PyOMe)₂en](ClO₄)₄ (2), which contain a full ligand bridging the two metal centers and a tridentate, non-bridging partially hydrolyzed ligand (PyR)enH₂. In contrast, the reaction with hydrated Ni(II) chloride resulted in [Ni((PyMe)₂en)Cl]₂Cl₂ (3) and [Ni(PyOMe₂(en))Cl]₂[NiCl₄] (4), which do not contain hydrolyzed ligand in the coordination sphere. The effect of the metal center and the starting salt in promoting ligand hydrolysis is discussed. The biological activity including in vitro DNA binding and cleavage was also evaluated for complexes 1–4. Ethidium bromide displacement assays with calf thymus DNA showed concentration-dependent displacement and DNA binding for all complexes, with apparent binding constants between 4 and 6.5 × 10⁵ M⁻¹. Cu(II) complexes 1 and 2 were further able to cleave DNA in vitro, producing both single-nicked and double-nicked DNA, while the Ni(II) complexes 3 and 4 showed no DNA cleavage under the same conditions. Investigations into the cleavage by the Cu(II) complexes 1 and 2 revealed an oxidative mechanism, where the complexes utilize O₂⁻ and ¹O₂ as the primary radical oxygen species, with ·OH playing a lesser role in the activity.