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The DNA helix, containing a stacked array of aromatic base pairs, presents a novel medium in which electron transfer mediated by a molecular [pi]-stack can be investigated. To probe electron transfer through DNA, we have constructed duplex assemblies modified with photo- and redox-active probes and applied spectroscopic and electrochemical approaches to the study of DNA-mediated charge transport.
Photoinduced electron transfer between intercalators was examined as a function of distance in a series of small DNA duplexes covalently modified with ethidium (Et) and [...]. At distances up to 35 [...], electron transfer occurs on the subnanosecond time scale ([...]). In duplexes containing disruptive base mismatches, large decreases in electron-transfer yields are observed, confirming that the electron transfer pathway proceeds through the stacked base pairs. Hence, it was demonstrated for the first time that DNA-mediated electron transfer between intercalators is exceptionally efficient, only weakly dependent on distance, but highly sensitive to perturbations in base stacking.
To investigate a DNA base within the [pi]-stack as a reactant, ethidium-modified duplexes containing the base analogue deazaguanine were synthesized. The photooxidation of deazaguanine by ethidium also proceeds on a subnanosecond time scale ([...]) and exhibits a shallow distance dependence. The efficiency and overall distance dependence is sensitive to the stacking of deazaguanine as determined by flanking sequence. These studies again showed that the DNA base stack can mediate extremely fast, long-range charge transport, and further elucidated that stacking interactions are critical in modulating the efficiency of this phenomenon.
Using base-base photochemistry, electron transfer through DNA was probed directly without external donors and acceptors. Using fluorescent analogues of adenine that selectively oxidize guanine, electron transfer through the DNA [pi]-stack was investigated as a function of reactant stacking and energetics. Small variations in each of these factors lead to remarkable changes in the kinetics of DNA-mediated electron transfer and values of [beta], a parameter reflecting the exponential dependence of electron transfer on distance, were measured ranging from [...] to [...]. The DNA base stack was shown to exhibit insulator to "wire"-like properties, depending on the structure and energetics of reactants employed to probe this medium.
To investigate DNA-mediated electron transfer using electrochemical methods, we assembled DNA films and incorporated intercalating redox-active molecules into the monolayers. Surface characterization techniques were employed to determine the orientation of the DNA helices within the films. With the intercalator daunomycin crosslinked to DNA duplexes immobilized on gold, efficient electron transfer over distances greater than 30 [...] was observed. Base mismatches also attenuate this long-range reaction, providing a new method for the electrochemical detection of genomic mutations.
These studies have provided essential measurements of electron transfer in DNA over known, fixed distances. It is now apparent that stacking interactions modulate the efficiency of this phenomenon, an observation that may explain the range of conflicting results reported within this field. Moreover, as experimental evidence increasingly supports the notion that ultrafast charge transport can occur through the DNA helix over long distances, the implications for biological systems can now be considered. Our findings point to the DNA [pi]-stack as not only a carrier of genetic information, but also a pathway which is conducive to charge transport
