LAUSR

Abstract Cu(II) phenanthroline complexes are able to cleave DNA and show cytotoxic activity against cancer cells. Also, the biological activity of hydrazone-based compounds has been reported in the literature. This motivated us to combine these two systems. Hydrazone-functionalized phenanthroline ligands with acetyl and benzoyl substituents were synthesized and characterized. The DNA cleavage activity of the corresponding Cu(II) complexes 3 and 4 was compared to the one of the well-known [Cu(phen)2]2+ complex (1) and [Cu(phenD)2]2+ complex (2, phenD = 1,10-phenanthroline-5,6-dione, the precursor of hydrazone-functionalized phenanthrolines). In the presence of ascorbate, but also in its absence, oxidative cleavage of DNA was proven by quenching therein involved reactive oxygen species (ROS), specifically hydrogen peroxide and superoxide anion radicals. Only complexes 2–4 were active in the absence of ascorbate, but not [Cu(phen)2]2+ (1). The surprising occurrence of ROS in the absence of any activating agent indicates that 2–4 represent self-activating artificial metallonucleases. Thereby, self-activation was most prominent for the novel hydrazone-based complexes 3 and 4. Cyclic voltammetry and circular dichroism spectroscopy were applied to get an insight in redox behavior and DNA binding characteristics of the Cu(II) complexes and thus to explain their different nuclease activity.