Investigations of DNA-Mediated Electron Transfer Reactions with Metallointercalators

The array of π-stacked base pairs in DNA represents a novel medium for electron transfer reactions, and metallointercalators have served as useful tools to study this chemistry. Ultrafast kinetic measurements indicate that photoinduced electron transfer reactions between M(phen)2(X2dppz)2+ (M = Ru, Os; dppz = dipyrido[3,2-a:2,3-c]phenazine; X = H, CH3) [M(II)] and Rh(phi)2bpy3+ (phi = phenanthrenequinone diimine) [Rh(III)] can occur with rates> 3 x 1010 s-1. Recombination reactions between M(III) and Rh(II) are also very fast (~ 1010 s-1), and rates are found to be independent of the loading of Δ-Rh(phi)2bpy3+ on DNA. However, reaction rates and efficiencies are highly sensitive to i) the structure and chirality of intercalators and ii) the sequence and conformation of the DNA double helix. Photoinduced reactions between Ru(II) and Rh(III) bound to the DNA helix and to SOS micelles, which lack the ordered π-stacked array, are also compared. In contrast to DNA, quenching in micelles occurs by diffusion. The details of intercalation and DNA sequence are thus found to be important characteristics of DNA-mediated ET reactions. To study long-range reactions through DNA, metallointercalator-DNA conjugates have been prepared. Rh(III) and novel trisheteroleptic complexes of Ru(II) are tethered to the 5'-termini of oligonucleotides by solid- and solution-phase methods, and these complexes have provided spectroscopic and photochemical tools to characterize chimeric structures. In addition to experiments in which DNA serves as a molecular bridge connecting donor and acceptor, the double helix may also serve as a reactant in electron transfer chemistry. Ru(III) oxidants have been generated in situ by a flash-quench methodology and have been found, by transient absorption spectroscopy, to oxidize G residues in DNA. Furthermore, using a tethered Ru(III)-DNA conjugate, oxidation products are observed 37 Å from the metallointercalator. These investigations of DNA-mediated electron transfer reactions contribute to our understanding of oxidative damage in DNA and may lead to a novel class of DNA-based biosensors.