Direct spectroscopic observation of 8-oxo-7,8-dihydro-2 '-deoxyguanosine radicals in double-stranded DNA generated by one-electron oxidation at a distance by 2-aminopurine radicals
V. Shafirovich et al., Direct spectroscopic observation of 8-oxo-7,8-dihydro-2 '-deoxyguanosine radicals in double-stranded DNA generated by one-electron oxidation at a distance by 2-aminopurine radicals, J PHYS CH B, 105(2), 2001, pp. 586-592
Oligonucleotide duplexes (15-mers) containing 8-oxo-7,8-dihydro-2'-deoxygua
nosine (8-oxo-dG) and the base analogue 2-aminopurine (2AP) separated from
one another by zero, two, or four thymidine residues on the same strand, we
re synthesized. Selective two-photon excitation of 2AP with intense 308 nm
XeCl excimer laser pulses (fwhm = 12 ns, similar to 80 mJ pulse(-1) cm(-2))
gives rise to 2AP radical cations that, in turn, oxidize 8-oxo-dG at a dis
tance. Transient absorption techniques allowed for the direct monitoring of
the oxidant and product radical intermediates as a function of time on the
100 ns-1 ms time scale and revealed the existence of two-component oxidati
on kinetics. The evolution in time of the rapid component (<100 ns), attrib
uted to the oxidation of 8-bxo-dG by the radical cation 2AP<bullet>(+), was
not resolved. However, this component was observed only in the case of zer
o or two intervening thymidine bases and was not evident when the 2AP and 8
-oxo-dG residues were separated by four thymidines. A slower kinetic compon
ent (> 100 ns) is attributed to the oxidation of 8-oxo-dG by the deprotonat
ion product of 2AP . (+), the neutral radical 2AP(-H).. Only the slow, micr
osecond kinetic component was observed when the 8-oxo-dG and 2AP an separat
ed by four thymidines. The rate constants of electron transfer are (3.8 +/-
0.5) x 10(4) s(-1) and (3.0 +/- 0.5) x 10(3) s(-1) in the case of two and
four intervening thymidines. respectively. Because of the pK(a) properties
of the donor/acceptor couples, this slow, 0.1-1000 mus time scale electron
transfer at a distance from 8-oxo-dG to the 2AP(-H) radicals, is likely to
occur via a proton-coupled electron-transfer mechanism.