New unsymmetric dinuclear CuIICuII complexes and their relevance to copper(II) containing metalloenzymes and DNA cleavage

The new homodinuclear complexes, [Cu2II(HLdtb)(μ-OCH3)](ClO4)2 (1) and [Cu2II(Ldtb)(μ-OCH3)](BPh4) (2), with the unsymmetrical N5O2 donor ligand (H2Ldtb) – {2-[N,N-Bis(2-pyridylmethyl)aminomethyl]-6-[N′,N′-(3,5-di-tert-butylbenzyl-2-hydroxy)(2-pyridylmethyl)]aminomethyl}-4-methylphenol have been synthesized and characterized in the solid state by X-ray crystallography.In both cases the structure reveals that the complexes have a common {CuII(μ-phenoxo)(μ-OCH3)CuII} structural unit.Magnetic susceptibility studies of 1 and 2 reveal J values of −38.3 cm−1 and −2.02 cm−1, respectively, and that the degree of antiferromagnetic coupling is strongly dependent on the coordination geometries of the copper centers within the dinuclear {CuII(μ-OCH3)(μ-phenolate)CuII} structural unit.Solution studies in dichloromethane, using UV–Visible spectroscopy and electrochemistry, indicate that under these experimental conditions the first coordination spheres of the CuII centers are maintained as observed in the solid state structures, and that both forms can be brought into equilibrium ([Cu2(HLdtb)(μ-OCH3)]2+ = [Cu2(Ldtb)(μ-OCH3)]+ + H+) by adjusting the pH with Et3N (Ldtb2− is the deprotonated form of the ligand).On the other hand, potentiometric titration studies of 1 in an ethanol/water mixture (70:30 V/V; I = 0.1 M KCl) show three titrable protons, indicating the dissociation of the bridging CH3O− group.The catecholase activity of 1 and 2 in methanol/water buffer (30:1 V/V) demonstrates that the deprotonated form is the active species in the oxidation of 3,5-di-tert-butylcatechol and that the reaction follows Michaelis–Menten behavior with kcat = 5.33 × 10−3 s−1 and KM = 3.96 × 10−3 M. Interestingly, 2 can be electrochemically oxidized with E1/2 = 0.27 V vs.Fc+/Fc (Fc+/Fc is the redox pair ferrocinium/ferrocene), a redox potential which is believed to be related to the formation of a phenoxyl radical.Since these complexes are redox active species, we analyzed their activity toward the nucleic acid DNA, a macromolecule prone to oxidative damage.Interestingly these complexes promoted DNA cleavage following an oxygen dependent pathway.