Charge Transfer through the DNA Base Stack

Abstract

AbstractWhether the DNA base pair stack might serve as a medium for efficient, long‐range charge transfer has been debated almost since the first proposal of the double‐helical structure of DNA. The consequences of long‐range radical migration through DNA are important with respect to understanding carcinogenesis and mutagenesis. Double‐helical DNA has in its core a stacked array of aromatic heterocyclic base pairs, and this molecular π stack represents a unique system in which to explore the chemistry of electron transfer. We designed a family of metal complexes which bind to DNA by intercalative stacking within the helix; these metallointercalators may be usefully applied in probing DNA‐mediated electron transfer. Here we describe a range of electron transfer reactions we carried out which are mediated by the DNA base paired stack. In some cases, DNA serves as a bridge, and spectroscopic analyses permit us to probe how the π stack couples DNA‐bound donors and acceptors. These studies point to the sensitivity of coupling to DNA intercalation. However, if the DNA π stack effectively bridges donors and acceptors, the base‐pair stack itself might serve not only as a conduit for electron transfer in DNA, but also in reactions initiated from a remote position. We carried out a series of reactions involving oxidative damage to DNA arising from the remotely positioned oxidant on the helix. The implications of long‐range charge migration through DNA to effect damage are substantial. As in other DNA‐mediated charge transfers, these reactions are highly dependent on DNA intercalation and the integrity of the intervening base‐pair stack, but not on molecular distance. Furthermore, a physiologically important DNA lesion, the thymine dimers, can be reversed in a reaction initiated by electron transfer. This repair reaction can also be promoted from a distance as a result of long‐range charge migration through the DNA base pair stack.