Copper-dioxygen complexes and their roles in biomimetic oxidation reactions - Advances in Catalytic Activation of Dioxygen by Metal Complexes - page 115

DNA to nicked under these conditions when complexed with copper. 143
Although the exact mechanism is unknown, the ligand is suspected to act as
an internal reducing agent, generating the copper(I) species. Addition of
hydrogen peroxide to the reaction results in an enhancement of the nuclease
activity. The cleavage reaction with peroxide was inhibited by radical, and
scavengers suggesting an oxidative cleavage mechanism similar to those
already discussed. However, addition of the same scavengers to the reaction
without peroxide resulted in no inhibition.
Less work has been done with other types of ligand systems. DNA
cleavage has been observed for alkylresorcinols with copper and 144 As in
the case of the (phenanthroline)-copper system, the active complex is
generated in situ. Addition of a copper(I) specific chelator, which suppressed
the reaction, demonstrated that Cu(I) is an obligatory intermediate in the
reaction and quenching by a radical scavenger and catalase showed that
hydroxyl radical and play important roles. 145 Two other natural
products have been isolated that give rise to oxidative cleavage of DNA in the
presence of copper. 146,147 In both cases, the reactive species is believed to be
formed by oxidation of the ligand to give a cation and Cu(I), which
can then react with dioxygen. This observation is supported by the complete
inhibition of the reaction by catalase. A freely diffusible hydroxyl radical was
ruled out by the failure of radical scavengers to inhibit the reaction.
Despite the high DNA cleavage activity of copper and copper
complexes in conjunction with dioxygen, very few compounds have been as
thoroughly studied as the phenanthroline-copper system. All of the above
chemistry shares in common a dependence on copper and hydrogen peroxide
with the reactive species responsible for DNA cleavage believed to be either
hydroxyl radical or a coordinated isoform. Some of the results regarding
specificity are conflicting, particularly for reactions with copper ion. In
general, for a compound not possessing a recognition unit, any degree of
specificity derives from the local structure of the duplex determined by the