Bis(acetato)bis(1-methyl-4,5-diphenylimidazole)copper(II): Preparation, characterization, crystal structure, DNA strand breakage and cytogenetic effect

The preparation, characterization and antitumour properties of the complex [Cu(O2CMe)(2)L-2] (1), where L = 1-methyl-4,5-diphenylimidazole, are described. The crystal structure of 1 (triclinic, space group P (1) over bar, a = 6.743(1), b = 8.006(1), c = 15.898(1) Angstrom, alpha = 102.87(1), beta = 101.10(1), gamma = 76.76(1)degrees, Z = 1) has been determined (R = 0.0254, R-w = 0.0275). In the centrosymmetric complex the copper ion is in an essentially square planar environment consisting of two pyridine-type imidazole nitrogen atoms and an oxygen atom from each acetate ligand; the second oxygen atoms of the carboxylate functionalities are involved in weak interactions with the metal completing the coordination to a very distorted tetragonal bipyramid. Complex 1 has been also characterized by elemental analyses, thermal methods, variable-temperature magnetic susceptibility and spectroscopic (IR and far-IR, FT-Raman, UV/VIS, EPR) techniques. The effect of the complex on the in vitro DNA strand breakage was examined. It was found that 1 causes degradation on the linearized pKS DNA, ds and ss DNA. High concentrations of this Cu(II) complex cause scissions on the relaxed and the supercoiled DNA. Furthermore, the in vivo cytogenic effect of 1 was examined on human lymphocyte cells. This study presents indications that 1 could have some relevance in the treatment of tumour cell lines. An orbital interpretation of the interaction of 1 with the DNA bases is proposed. (C) 1998 Elsevier Science Inc. All rights reserved.