Steric effect on the nuclease activity of Cu(II) complexes with aminoquinoline derivatives

Three copper(II) complexes of aminoquinoline derivatives, l-glycine-N′-8-quinolylamide (L1), l-alanine-N′-8-quinolylamide (L2), and N-(8-quinolyl) pyridine-2-carboxamide (L3) have been shown to cleave plasmid DNA pBR322 and pUC18 with or without the presence of H2O2/ascorbate. Crystallographic data reveal that the Cu(II) coordination plane in [Cu(L1)(Ac)(H2O)] (1) and [Cu(L2)(Ac)] (2) is nearly co-planar with the quinoline ring. The cleavage activity follows the order of complex 1 > complex 2 > complex 3, which is in agreement with the reverse order of the steric hindrance of the amino-substituent of the ligands. The presence of the standard radical scavengers does not have a clear effect on the cleavage efficiency of the Cu(II) complexes, suggesting the reactive species leading to DNA damage could be DNA-bound copper-centered radicals rather than the free diffusible ones.