Unique ligand-based oxidative DNA cleavage by zinc(II) complexes of hpyramol and hpyrimol

Abstract

The zinc(II) complexes reported here have been synthesised from the ligand 4-methyl-2-N-(2-pyridylmethyl)aminophenol (Hpyramol) with chloride or acetate counterions. All the five complexes have been structurally characterised, and the crystal structures reveal that the ligand Hpyramol gradually undergoes an oxidative dehydrogenation to form the ligand 4-methyl-2-N-(2-pyridylmethylene)aminophenol (Hpyrimol), upon coordination to Zn-II. All the five complexes cleave the phi X174 phage DNA oxidatively and the complexes with fully dehydrogenated pyrimol ligands were found to be more efficient than the complexes with non-dehydrogenated Hpyramol ligands. The DNA cleavage is suggested to be ligand-based, whereas the pure ligands alone do not cleave DNA. The DNA cleavage is strongly suggested to be oxidative, possibly due to the involvement of a non-diffusible phenoxyl radical mechanism. ne enzymatic religation experiments and DNA cleavage in the presence of different radical scavengers further support the oxidative DNA cleavage by the zinc(II) complexes.