From Cyclen to 12-Crown-4 Copper(II) Complexes: Exchange of Donor Atoms Improves DNA Cleavage Activity

Macrocyclic Cu-II complexes with [NXOY] donor sets of different N/O ratios were synthesised resulting in a series ranging from cyclen (X = 4, Y = 0: 1) to 12-crown-4 (X = 0, Y = 4: 6) complexes. In order to elucidate the structure of the complexes UV/Vis spectroscopy and X-ray crystallography were applied, focusing especially on the literature-unknown compounds with regioisomeric [N2O2] and [NONO] donor sets (3, 4). The complexes were subjected to DNA cleavage experiments under reducing conditions and were also tested in the absence of a reducing agent. Although 3 and 6 were the most active DNA cleavers in the presence of reducing ascorbate, both of them and 4 also cleaved DNA (not hydrolytically) in its absence. This brings up questions regarding the cleavage mechanism. The present study is an expansion of our previously reported finding that heterosubstitution in macrocyclic ligands leads to changes in oxidative DNA cleavage activity of Cu-II complexes.