The Interaction between Hydrogen Peroxide and the DNA -Cu (I) Complex: Effects of pH and Buffers

The rate of interaction between H and the DNA -Cu (I) complex increases with pH and with salt (NaCl) concentration, suggesting that HO is involved. The pH dependence can be fitted, assuming k(DNA - Cu(I) + H ) = 1 м s-1 and k (DNA -Cu(I) + HO ) = 10 м s (at low salt concentrations). These interactions cause DNA damage, probably due to the for­mation of OH radicals near the site of Cu(I) fixation at DNA bases. About 70% of the inter­mediates DNA OH , formed by free OH radicals, were found capable of reducing Cu(II) to regenerate DNA -Cu (I); thus a (limited) reaction chain involving “reductive propagation” by DNA OH species appears feasible upon reaction of H with DNA -Cu (I). OH-induced in­termediates of poly(C) are more efficient (about 80%), those of poly(A) and poly(G) are less efficient (about 38%), in reducing Cu(II). Certain organic buffers, particulary HEPES and PIPES, promote autoxidation in DNA /Cu (II)/H systems, and it is shown that OH-induced buffer intermediates as well as secondary stable buffer products can engage in “reductive propagation” of redox cycles.