The interaction between hydrogen peroxide and the DNA-Cu(I) complex: effects of pH and buffers

The rate of interaction between H2O2 and the DNA-Cu(I) complex increases with pH and with salt (NaCl) concentration, suggesting that HO2- is involved. The pH dependence can be fitted, assuming k(DNA-Cu(I) + H2O2) = 1 M-1 S-1 and k(DNA-Cu(I) + HO2-) = 10(5) M-1 S-1 (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 H2O2 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, particularly HEPES and PIPES, promote autoxidation in DNA/Cu(II)/H2O2 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.