Forty Years after the Discovery of Its Nucleolytic Activity: [Cu(phen)2 ]2+ Shows Unattended DNA Cleavage Activity upon Fluorination

Abstract

[Cu(phen)₂ ]²⁺ (phen=1,10-phenanthroline) is the first and still one of the most efficient artificial nucleases. In general, when the phen ligand is modified, the nucleolytic activity of its Cu^II complex is significantly reduced. This is most likely due to higher steric bulk of such ligands and thus lower affinity to DNA. Cu^II complexes with phen ligands having fluorinated substituents (F, CF₃ , SF₅ , SCF₃ ) surprisingly showed excellent DNA cleavage activity-in contrast to the unsubstituted [Cu(phen)₂ ]²⁺ -in the absence of the otherwise required classical, bioabundant external reducing agents like thiols or ascorbate. This nucleolytic activity correlates well with the half-wave potentials E_1/2 of the complexes. Cancer cell studies show cytotoxic effects of all complexes with fluorinated ligands in the low μm range, whereas they were less toxic towards healthy cells (fibroblasts).

Keywords: artificial nucleases; copper complexes; cytotoxicity; fluorination; phenanthroline.