Influence of the copper coordination geometry on the DNA cleavage activity of Clip-Phen complexes studied by DFT

Six different Cu(Chp-Phen)(2+/+) complexes, with or without a coordinating chloride ligand, have been investigated by DFT calculations to evaluate the influence of the length and functional substituents of the bridge linking the two phenanthroline units on the DNA cleavage activity. The changes of the structural and energetic profiles imposed by the bridge of these complexes have been analyzed by comparison with the well studied nuclease active agent Cu(phen)(2)(2+/+). The present studies show that the bridge length of these complexes is critical for the consequent geometry, and both the strain and ligand binding energies. Upon reduction (needed for the DNA cleavage activity), the geometry of Cu(phen)(2) changes drastically. The behavior of the complexes with a 4- or 5-carbon bridge resembles the behavior of Cu(phen)(2)(2+/+). However, the geometries of the complexes with two- or three-carbon bridges are markedly different from the one of unbridged Cu(phen)(2)(+), as a result of constraints enforced by the short bridge. The results suggest that the cleaving activities of these bis-phenanthroline complexes are influenced by the different ligand environment geometries imposed by the bridge, and not by the change of the redox properties. It appears that the influence of the different bridges on the redox properties of the complexes is minor. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).