Effects of strand and directional asymmetry on base–base coupling and charge transfer in double-helical DNA

Abstract

Mechanistic models of charge transfer (CT) in macromolecules often focus on CT energetics and distance as the chief parameters governing CT rates and efficiencies. However, in DNA, features unique to the DNA molecule, in particular, the structure and dynamics of the DNA base stack, also have a dramatic impact on CT. Here we probe the influence of subtle structural variations on base-base CT within a DNA duplex by examining photoinduced quenching of 2-aminopurine (Ap) as a result of hole transfer (HT) to guanine (G). Photoexcited Ap is used as a dual reporter of variations in base stacking and CT efficiency. Significantly, the unique features of DNA, including the strandedness and directional asymmetry of the double helix, play a defining role in CT efficiency. For an (AT)n bridge, the orientation of the base pairs is critical; the yield of intrastrand HT is markedly higher through (A)n compared with (T)n bridges, whereas HT via intrastrand pathways is more efficient than through interstrand pathways. Remarkably, for reactions through the same DNA bridge, over the same distance, and with the same driving force, HT from photoexcited Ap to G in the 5 to 3 direction is more efficient and less dependent on distance than HT from 3 to 5 . We attribute these differences in HT efficiency to variations in base-base coupling within the DNA assemblies. Thus base-base coupling is a critical parameter in DNA CT and strongly depends on subtle structural nuances of duplex DNA.T he transport of electronic charge through double-helical DNA continues to fascinate and surprise us (1-5). A wealth of experimental evidence has established, undeniably, that DNA can act as a conduit for rapid and long-range charge transfer (CT), not only in DNA assemblies designed in the laboratory (6-24), but also in biologically significant environments (25,26). DNA, remarkable for its role in the molecular basis of life, may also play a role as a mediator of CT in diverse areas of chemistry and biology. Indeed, the ability of DNA to mediate CT and the exquisite sensitivity of this chemistry to DNA structure has spawned the development of a completely new family of diagnostic tools (27,28). Yet, while we continue to probe and exploit the distinctive ability of DNA to transport charge, fundamental questions concerning the mechanisms and features of DNA CT remain.We investigate DNA CT by using a combination of spectroscopic, biochemical, and electrochemical tools to interrogate well-characterized assemblies that incorporate redox-active molecules from a large repertoire including metallointercalators, organic intercalators, and modified DNA bases (6)(7)(8)(9)(10)(11)(12)(25)(26)(27)(28). Consistently, we have observed that DNA CT is remarkably sensitive to the structure and dynamics of the DNA bases. Experiments in which the DNA base stack is altered by, for instance, sequence variation (10), mismatches (9, 28), structural perturbations (11), or protein binding (12,27) emphasize the importance of the integrity of the -stack to DNA CT. In addition, time-...

Integration specificity of LTR-retrotransposons and retroviruses in the Drosophila melanogaster genome

“…The biological sense of the A-form formation is not sufficiently clear. Double-strand RNA and RNA-DNA-hybrids are shown to exist in the A-form [21]. The transition from B-form to the A-form appears to be observed at a DNA-RNA polymerase complex.…”

Energetics of the hole transfer in DNA duplex oligomers

“…For others the π orbitals are localized mostly on one nucleobase, and we can consider the weak intrastrand and interstrand coupling between the nucleobases as well. The low interstrand coupling for the cases A-T/T-A and G-C/C-G has been observed experimentally [28].…”

UV excitation of single DNA and RNA strands produces high yields of exciplex states between two stacked bases

“…This could lead to electron transfer in a specific direction in purine-purine dimers like ApA and ApG because of differences in electronic coupling arising from basebase overlap (28). The directional asymmetry of electron transfer quenching of 2-aminopurine fluorescence in DNA has been extensively discussed by Barton and coworkers (29). Electron transfer in ApG is plausibly from G, the most readily oxidized base, to A, but the energy of neither the A Ϫ pG ϩ nor the A ϩ pG Ϫ exciplex is well correlated with the observed rate.…”

“…The small separation of 3.4 Å between stacked bases facilitates charge-transfer quenching of excited 2AP (29,33). It is also responsible for the excimer/exciplex fluorescence seen from excited dinucleosides at 77 K (34).…”