Recognition and oxidative strand scission of nucleic acids by multinuclear copper(II) coordination complexes

The compound [Cu2II(D1 )(H2O)2](ClO4)4·2H 2O mediates efficient oxidative cleavage of DNA under conditions conducive for reduction of the metal centers and subsequent activation of dioxygen. Relative to a mononuclear analogue, the binuclear complex more rapidly effects degradation of both plasmids and oligonucleotides. Cleavage requires both the complex and a reductant and likely proceeds through a nondiffusible O 2-derived intermediate, the formation of which may be dependent on the presence of multiple metal ions in the same complex.;A trinuclear copper complex, [Cu3II( L)(H2O)3(NO3)2](NO 3)4·5H2O, exhibits a remarkable ability to promote specific strand scission at helix/coil junctions. Strand scission occurs on the 3' overhang at the junction of a hairpin or frayed duplex structure and is not dependent on the identity of the base at which cleavage occurs. Target recognition minimally requires a purine at the first unpaired position and a guanine at the second unpaired position on the 5' extension. Selective strand scission requires both a reductant and dioxygen and does not appear to involve a diffusible radical. Comparisons between the trinuclear copper complex and mononuclear compounds indicate that the recognition and reactivity described in this report are also dependent on the multinuclearity of the complex.;The compound [Cu2II(D1 )(H2O)2](ClO4)4 also selectively promotes cleavage of DNA on nucleotide strands that extend from the 3 ' side of frayed duplex structures at a site two residues displaced from the junction. The minimal requirements for reaction include a guanine in the first unpaired position of the 3' overhang adjacent to the cleavage site and an adenine in the parallel position on the 5 ' overhang. Recognition and strand scission are independent of the nucleobase at the cleavage site. The necessary presence of both a reductant and dioxygen indicates that the intermediate responsible for cleavage is produced by the activation of dioxygen by a copper(I) form of the binuclear complex. The unique coordination and reactivity properties of [Cu2 II(D1)(H2O)2](ClO 4)4 are critical for its efficiency and site selectivity since mononuclear compounds and a binuclear analogue exhibit only nonselective cleavage of DNA.