The function of DNA during oxidative stress and its suitability as a potential building block for molecular devices depend on long-distance transfer of electrons and holes through the molecule, yet many conflicting measurements of the efficiency of this process have been reported. It is accepted that charges are transported over long distances through a multistep hopping reaction; this 'G-hopping' involves positive charges moving between guanines (Gs), the DNA bases with the lowest ionization potential. But the mechanism fails to explain the persistence of efficient charge transfer when the guanine sites are distant, where transfer rates do not, as expected, decrease rapidly with transfer distance. Here we show experimentally that the rate of charge transfer between two guanine bases decreases with increasing separation only if the guanines are separated by no more than three base pairs; if more bridging base pairs are present, the transfer rates exhibit only a weak distance dependence. We attribute this distinct change in the distance dependence of the rate of charge transfer through DNA to a shift from coherent superexchange charge transfer (tunnelling) at short distances to a process mediated by thermally induced hopping of charges between adenine bases (A-hopping) at long distances. Our results confirm theoretical predictions of this behaviour, emphasizing that seemingly contradictory observations of a strong as well as a weak influence of distance on DNA charge transfer are readily explained by a change in the transfer mechanism.

Mechanistic investigations of the photoinduced DNA damage by acridizinium salts (4a-azonia-anthracene derivatives) are presented. Irradiation of 9-bromoacridizinium in the presence of defined double- and single-stranded DNA oligomers under aerobic conditions leads to both frank strand breaks and alkali-labile sites as determined by polyacrylamide gel electrophoresis (PAGE). The extent of the DNA damage increases significantly in D(2)O and occurs selectively at guanosine residues. These observations reveal the formation of singlet oxygen ((1)O(2)) as reactive species, which oxidizes the DNA bases, above all the guanine bases. Further evidence for (1)O(2) formation was obtained from laser-flash spectroscopic investigations, which show intersystem crossing (S(1) to T(1)) of the excited states of the parent acridizinium and of the 9-bromo- and 9-amino-substituted derivatives. The resulting triplet state is efficiently quenched by oxygen (k(q) > 10(9) s(-)(1)M(-)(1)) to yield (1)O(2). Under anaerobic conditions, no significant alkali-labile lesions are observed, but frank strand breaks are induced; however, to lesser extent than under aerobic conditions. The DNA damage is suppressed in the presence of a radical scavenger, namely t-BuOH, and hydroxyl radicals are shown to be the reactive intermediates by trapping experiments with terephthalic acid. Moreover, the intercalated acridizinium molecules are not involved in the DNA damage reactions. The intercalated acridizinium salt leads to a primary PET reaction with the DNA bases; however, a fast BET transfer is proposed that regains the dye and the DNA, so that the excited intercalated dye does not contribute significantly to the overall DNA damage.

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