[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 mu m range, whereas they were less toxic towards healthy cells (fibroblasts).