A Hydroxyl-bridged Dinuclear Copper Complex Having Planar Structure Shows Efficient DNA Cleavage Activity in Aqueous Solution

A new dinuclear copper(II) complex, [Cu(DPA)OH](2)center dot 2ClO(4)(Cu-2-DPA(2), DPA = di(pyridin-2-yl) amine), was synthesized and structurally characterized. The complex crystallized in a triclinic P-1 space group, taking on a slightly distorted tetragonal geometry. Both Cu(II) in Cu-2-DPA(2) are bridged by two hydroxyl groups with a distance of 2.938 angstrom. The whole molecule is nearly co-planar with the exception of the bridging hydroxyl groups. Complex Cu-2-DPA(2) can cleave efficiently supercoiled pBR322 DNA into its nicked and linearized forms at micromolar concentrations in the presence of ascorbate near physiological conditions. The presence of standard radical scavengers does not have any apparent effect on the cleavage efficiency, suggesting that Cu(II) bound oxygen intermediates rather than freely diffusible hydroxyl radicals may act as the active species in the DNA scission. Comparison of the cleavage reactivity of Cu-2-DPA(2) with that of mononuclear analogue Cu-DPA and trinuclear Cu-3-L demonstrates that the synergistic effect between Cu(II) centers in Cu-2-DPA(2) is crucial for the DNA cleavage.