Copper-dioxygen complexes and their roles in biomimetic oxidation reactions - Advances in Catalytic Activation of Dioxygen by Metal Complexes - page 113

Due to the role of the ligand in tuning the redox potential of metal
ions in a complex, there are examples of compounds that are both more and
less reactive than uncomplexed copper. The best studied and to-date most
reactive DNA-cleavage systems are based on the bis(1,10-
phenanthroline)cuprous complex, The reduction of the
(phenanthroline)cupric complex by mercaptopropionic acid usually initiates
the reaction to give the cuprous form and a disulfide. (Eq. 1) The cuprous
complex can then react with dioxygen yielding superoxide and the copper(II)
starting material. (Eq. 2) Spontaneous dismutation of superoxide in the
presence of protons produces hydrogen peroxide and dioxygen. (Eq. 3)
Strand scission results from interaction of hydrogen peroxide with the cuprous
compound bound in the minor groove of the DNA duplex. The identity of the
reactive intermediate has yet to be determined; although, inhibition studies
like those done with copper ions suggest that a diffusible radical is not
involved. Other possibilities include
The major reaction pathway was thought to proceed via hydrogen
atom abstraction at the C-1' position of the deoxyribose giving a 2'-
deoxyribonolactone intermediate and resulting in 5'-phosphate, 3'-phosphate,
5-methylene furanone, and free base as products (Scheme 14). Recent work
showed that the carbonyl oxygen of the 5-methylene furanone is derived from
water and a 1',2'dehydronucleotide was proposed as the intermediate. 134
However, a mononucleotide analogue of the 1',2' dehydronucleotide did not
decompose to the observed cleavage products resulting from reaction of DNA
with Decomposition of a 2'-deoxyribonolactone model to 5-
methylene furanone and free phosphate suggested a catalyzed
elimination of the lactone intermediate. 135 A contradictory report discounted
both intermediates and proposed that direct strand scission is a result of H-
atom abstraction at the C-4' and C-5' positions with C-1' abstraction
producing alkaline labile sites, but not strand breaks. 136 Under certain
conditions, a secondary reaction at the C-4' position is also observed yielding
5'-phosphate, 3'-phosphoglycolate, and an unidentified 3-carbon fragment. 137