Book of Abstracts: Albany 2005
DNA Charge Transport in Ruthenium-modified Assemblies
It is now well recognized that the pi-stack of the DNA double helix can serve as a mediator of charge transport and it has been shown that these reactions through DNA can span distances as great as 200 Å. Charge transfer events resulting in oxidation of DNA bases have particular relevance in areas such as ageing and in many diseases including cancer and neurogenerative disorders. Guanine, acting as an electron donor or hole trap, is the most readily oxidized of the naturally occurring bases. Upon oxidation, the neutral guanine radical can react irreversibly with water or oxygen to form damage products such as 8-oxo-G, oxazolone, and imidazolone.
Here we explore charge transport in ruthenium modified DNA assemblies using EPR and transient absorption spectroscopies combined with biochemical methods; the artificial base 4-methyl indole is also used as a spectroscopic probe in transient absorption studies. The 4-methyl indole radical cation has been characterized by EPR and transient absorption spectroscopies using the flash quench technique with a dipyridophenazine complex of ruthenium acting as the intercalating oxidant. The rate of formation of the indole radical cation is 107s-1 for different DNA assemblies in which the ruthenium is positioned 17-37 Å away from the methylindole and with an intervening bridge comprised primarily of A-T base pairs. In these assemblies, the formation of the methyl indole radical is concomitant with the quenching of the ruthenium excited state to form Ru(III). Thus, the quenching reaction is rate limiting and DNA charge transport is in fact much faster. Hole hopping along G sites and tunnelling through AT steps cannot account for these data. We propose transport along delocalized DNA domains. We have recently designed a hybrid complex in which the quencher is covalently tethered to the ruthenium photooxidant in hope of monitoring charge transfer rates through DNA on a still faster timescale.
Katherine E. Augustyn