Copper-dioxygen complexes and their roles in biomimetic oxidation reactions - Advances in Catalytic Activation of Dioxygen by Metal Complexes - page 112

carry out predominantly direct strand scission to the near exclusion of
nucleobase chemistry, there are no examples of copper complexes that only
react with the bases. 122 Both types of reaction utilize a reactive oxygen
species, usually hydroxyl radical and are hydrogen peroxide dependent. For
clarification the numbering scheme for the sugar is presented herein. Because
of the limited and unspecific nature of reaction with the bases, their structures
and numbering are not presented. Distinctions will be made between
experiments that utilized restriction fragments or oligonucleotides to assess
cleavage and those which employed plasmid, a considerably more sensitive
assay, the results of which do not always correlate with work done on shorter
DNA fragments.
In the presence of thiols, ascorbate, or NADH, free copper ions have
been observed to facilitate direct strand scission of DNA. In the thiol-
dependent reaction, the observed reactivity remains unchanged despite the use
of different thiols suggesting that the reaction is independent of the nature of
the reductant, and proceeds through a copper(I) dioxygen intermediate which
generates hydroxyl radical as opposed to a thiyl or alkyl radical. 123-125 This is
confirmed by inhibition of the cleavage reaction with plasmids in the presence
of hydroxyl radical scavengers. 126 Contrarily, in the ascorbate case there
appears to be no inhibition by hydroxyl radical scavengers, while catalase
almost completely arrests the reaction, implicating hydrogen peroxide as an
essential component. 127,128 The previous statement also holds true for reaction
of Cu(II) and NADH with restriction fragments. 129 In all of the above cases
where a restriction fragment or oligonucleotide was treated with piperidine
after reaction with copper and an initiator, there was an observed
enhancement in the reaction. Piperidine treatment results in strand scission at
alkaline labile sites where the base has been removed or modified. The
enhancement is presumed to be due to base oxidation, although specific
products consistent with this assertion were not isolated or characterized.
There is also considerable reactivity with copper(II), hydrogen
peroxide and DNA. In the absence of another reagent such as thiol or
ascorbate, the reaction in the presence of can be quenched by the
addition of radical scavengers, suggesting that there are at least two different
mechanisms possible. In one instance, the researchers reported cleavage
selectivity for polyguanosines within a restriction fragment upon piperidine
treatment. 130 In a conflicting study, selectivity for thymine and guanine,
especially when located 5' to a guanine was shown. 131