Abstract: Copper (II) complexes of three phosphonate ligands were prepared and fully characterized by elemental analysis, spectral and thermal studies. The IR spectral data showed that the phosphonate compounds behave as bidentate ligands coordinating to the copper ion through the P=O and NH groups. The electronic spectroscopic data support a distorted octahedral geometry around copper ion. The activity of the phosphonate ligands and their copper (II) complexes as small molecules were investigated towards DNA cleavage. The phosphonate ligands showed no activity, while the copper complexes showed DNA cleavage. The copper (II) complex of Diphenyl (3-hydroxyphenylamino)(2-hydroxyphenyl)methylphosphonate showed the highest activity towards DNA cleavage.