DNA binding and nucleolytic properties of Cu(ii) complexes of salicylaldehyde semicarbazones

Abstract

The copper(II) complexes of two salicylaldehyde semicarbazones, HOC₆H₄CHN-NHCONR₂ [H₂Bnz₂ (R = CH₂Ph) and H₂Bu₂ (R = Bu)], were evaluated for their DNA binding and cleavage properties by spectrophotometric DNA titration, ethidium bromide displacement assay and electrophoretic mobility shift assay. Results showed that the Cu(II) complexes can bind to DNA via a partial intercalation mode with binding constants of 1.1 × 10⁴ and 9.5 × 10³ M⁻¹ for [Cu(HBnz₂)Cl] and [Cu(HBu₂)Cl], respectively. These complexes also cleave DNA in the presence of ascorbic acid, most likely through hydroxyl radicals that are generated via the reduction of a Cu(II) to a Cu(I) species. The complexes show similar DNA cleavage activity, which is reflected in the similarity of their frontier molecular orbital energies calculated by density functional theory. These results are discussed in relation to the anticancer properties of the complexes.