Copper-dioxygen complexes and their roles in biomimetic oxidation reactions - Advances in Catalytic Activation of Dioxygen by Metal Complexes - page 114

Using B-DNA as a substrate, (phenanthroline)-copper complexes will
react with every base, although there appears to be a slight preference for A

· T

stretches. There is no reaction with single-stranded DNA indicating that the
complex requires some secondary structure in the substrate for the reaction to
occur. This is supported by a decrease in reactivity with A-DNA and a lack
of reactivity with Z-DNA. 138 Covalent linkage of phenanthroline to an RNA
primer or a DNA binding protein allows for specific cleavage at the site of
interaction between the recognition unit and the DNA substrate. 139,140 In the
absence of a tethered DNA recognition unit there is limited specificity in the
observed cleavage.

The 1,10-phenanthroline-copper complex is usually generated in situ
where it exhibits maximal cleavage efficiency at a copper to phenanthroline
ratio of 1:4. This results from the smaller binding constant of the second
phenanthroline in the complex. At high thiol concentrations where there is
competitive binding between phenanthroline and the thiol this can be
problematic. By covalently attaching two phenanthrolines using a short

flexible arm containing an exogenous primary amine, a 2:1 phenanthroline-
copper complex can be maintained. 141 The new compound, “clip-phen” has
been shown to be more reactive than with plasmid DNA.
Vectorization of “clip-phen” at the amine using acridine, a known
intercalator, resulted in compounds possessing even greater reactivity. 142
Although, neither "clip-phen" nor phenanthroline:copper are capable of
mediating strand scission in the absence of a reductant, the ortho -quinacridine

compounds, and facilitate the conversion of supercoiled plasmid