The role of base motions in delocalization and propagation of charge through double helical DNA must be established experimentally and incorporated into mechanistic descriptions of DNA-mediated charge transport (CT). Here, we address these fundamental issues by examining the temperature dependence of the yield of CT between photoexcited 2-aminopurine (Ap*) and G through DNA bridges of varied length and sequence. DNA assemblies (35-mers) were constructed containing adenine bridges Ap(A) n G (n = 0−9, 3.4−34 Å) and mixed bridges, ApAAIAG and ApATATG. CT was monitored through fluorescence quenching of Ap* by G and through HPLC analysis of photolyzed DNA assemblies containing Ap and the modified guanine, N 2-cyclopropylguanosine (CPG); upon oxidation, the CPG radical cation undergoes rapid ring opening. First, we find that below the duplex melting temperature (∼60 °C), the yield of CT through duplex DNA increases with increasing temperature governed by the length and sequence of the DNA bridge. Second, the distance dependence of CT is regulated by temperature; enhanced DNA base fluctuations within duplex DNA extend CT to significantly longer distances, here up to 34 Å in <10 ns. Third, at all temperatures the yield of CT does not exhibit a simple distance dependence; an oscillatory component, with a period of ∼4−5 base pairs, is evident. These data cannot be rationalized by superexchange, hopping of a localized charge injected into the DNA bridge, a temperature-induced transition from superexchange to thermally induced hopping, or by phonon-assisted polaron hopping. Instead, we propose that CT occurs within DNA assemblies possessing specific, well-coupled conformations of the DNA bases, CT-active domains, accessed through base motion. CT through DNA is described as conformationally gated hopping among stacked domains. Enhanced DNA base motions lead to longer range CT with a complex distance dependence that reflects the roles of coherent dynamics and charge delocalization through transient domains. Consequently, DNA CT is not a simple function of distance but is intimately related to the dynamical structure of the DNA bridge.

The ultrafast dynamics of electron transfer (ET) between bases in DNA have been determined to elucidate the critical role of base‐pair gating on the timescale of the electron transport and the temperature dependence of the rates. ET occurs only through DNA duplexes that adopt a specific, well‐coupled alignment of bases (ET‐active; see picture). Descriptions of ET dynamics must include fluctuations of DNA bases.

Charge transport (CT) through DNA has been found to occur over long molecular distances in a reaction that is sensitive to intervening structure. The process has been described mechanistically as involving diffusive charge-hopping among low-energy guanine sites. Using a kinetically fast electron hole trap, N4-cyclopropylcytosine ( CP C), here we show that hole migration must involve also the higher-energy pyrimidine bases. In DNA assemblies containing either [Rh(phi)2(bpy )] 3؉ or an anthraquinone derivative, two highenergy photooxidants, appreciable oxidative damage at a distant CP C is observed. The damage yield is modulated by lower-energy guanine sites on the same or complementary strand. Significantly, the efficiency in trapping at CP C is equivalent to that at N2-cyclopropylguanosine ( CP G). Indeed, even when CP G and CP C are incorporated as neighboring bases on the same strand, their efficiency of photodecomposition is comparable. Thus, CT is not simply a function of the relative energies of the isolated bases but instead may require orbital mixing among the bases. We propose that charge migration through DNA involves occupation of all of the DNA bases with radical delocalization within transient structure-dependent domains. These delocalized domains may form and break up transiently, facilitating and limiting CT. This dynamic delocalized model for DNA CT accounts for the sensitivity of the process to sequence-dependent DNA structure and provides a basis to reconcile and exploit DNA CT chemistry and physics.charge transport ͉ delocalized domain ͉ radical trap ͉ base dynamics O xidative damage to DNA from a distance through longrange migration of charge has now been established in many DNA assemblies by using different pendant photooxidants through both biochemical and spectroscopic assays (1-8). The DNA base pair stack can mediate charge transport (CT) over at least 200 Å (2, 3), and the reaction is exquisitely sensitive to the dynamic structure and stacking within the DNA duplex (9, 10). This sensitivity to perturbations in base pair stacking has been advantageous in the development of DNA-based sensors for mutational analysis (11) and may provide a role for DNAmediated CT within the cell (12), but it has limited the application of physical techniques to explore CT mechanistically.Although not a robust molecular wire, the DNA duplex has in some experiments been characterized as a wide band gap semiconductor (13,14). More prevalent have been models of incoherent CT involving a mixture of localized charge-hopping among low-energy sites, guanines and sometimes adenines, and tunneling through higher-energy pyrimidine bases (15-18). These mechanisms do not provide a rationale, however, for the sensitivity of CT to DNA structure. We have observed that DNA CT is gated by the dynamical motions of the DNA bases (9, 19) and have described DNA CT as conformationally gated hopping through transient, well stacked DNA domains (20).Our experimental strategy to probe for hole density on pyrimidines exploits the rapid ...

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Spectroscopic techniques are employed to probe relationships between structural dynamics and charge transfer (CT) efficiency in DNA duplexes and DNA:RNA hybrids containing photoexcited 2-aminopurine (Ap). To better understand the variety of interactions and reactions, including CT, between Ap and DNA, the fluorescence behavior of Ap is investigated in a full series of redox-inactive as well as redox-active assemblies. Thus, Ap is developed as a dual reporter of structural dynamics and base-base CT reactions in nucleic acid duplexes. CD, NMR, and thermal denaturation profiles are consistent with the family of DNA duplexes adopting a distinct conformation versus the DNA:RNA hybrids. Fluorescence measurements establish that the d(A)-r(U) tract of the DNA:RNA hybrid exhibits enhanced structural flexibility relative to that of the d(A)-d(T) tract of the DNA duplexes. The yield of CT from either G or 7-deazaguanine (Z) to Ap in the assemblies was determined by comparing Ap emission in redox-active G- or Z-containing duplexes to otherwise identical duplexes in which the G or Z is replaced by inosine (I), the redox-inactive nucleoside analogue. Investigations of CT not only demonstrate efficient intrastrand base-base CT in the DNA:RNA hybrids but also reveal a distance dependence of CT yield that is more shallow through the d(A)-r(U) bridge of the A-form DNA:RNA hybrids than through the d(A)-d(T) bridge of the B-form DNA duplexes. The shallow distance dependence of intrastrand CT in DNA:RNA hybrids correlates with the increased conformational flexibility of bases within the hybrid duplexes. Measurements of interstrand base-base CT provide another means to distinguish between the A- and B-form helices. Significantly, in the A-form DNA:RNA hybrids, a similar distance dependence is obtained for inter- and intrastrand reactions, while, in B-DNA, a more shallow distance dependence is evident with interstrand CT reactions. These observations are consistent with evaluations of intra- and interstrand base overlap in A- versus B-form duplexes. Overall, these data underscore the sensitivity of CT chemistry to nucleic acid structure and structural dynamics.