DNA base pair stacking

Bixon and Jortner, Rosch and Voityuk, Olofsson and Larsson, Berlin, Burin, Siebbeles, and Ratner, Orlandi and their coworkers [4, 8, 19-31] have explored the energetics and base-base interactions associated with hole and electron transfer in DNA base-pair stacks. They find nearest-neighbor coupling inter-... 

Extended solid state n systems facilitate CT, particularly when doped [4-6]. The analogy between DNA and conductive solid state -stacks therefore establishes that a requisite condition for CT may exist in DNA. DNA contains an array of heterocyclic aromatic base pairs, stacked at a distance of 3.4 A, wrapped within a negatively charged sugar phosphate backbone [7] (Fig. 1). The interactions between the n electrons of the DNA base pairs provide the electronic coupling necessary for CT to occur. 

To test this sensitivity of photoinduced quenching to perturbations in the intervening base pair stack, an assembly was prepared containing an intervening CA base mismatch which disrupts locally the /r-stack between the donor and acceptor. We observed that the yield of CT was reduced in the DNA... 

The analogy drawn between -stacked solids and duplex DNA has provided a useful starting point for experiments to probe and understand DNA-medi-ated CT. As with the -stacked solids, the DNA base pair array can provide an effective medium for long range CT. Mechanistically, however, the differences between DNA and these solid state materials may be even more important to consider. Duplex DNA, as a molecular -stacked structure, undergoes dynamical motion in solution. The time-dependent and sequence-dependent structures that arise serve to modulate and gate CT. Indeed in probing DNA CT as a function of sequence and sequence-dependent structure, we may better understand mechanistically how CT proceeds and how DNA CT may be utilized. 

DNA CT also permits chemistry at a distance. Oxidative DNA damage and thymine dimer repair can proceed in a DNA-mediated reaction initiated from a remote site. These reactions too are sensitive to intervening DNA dynamical structure, and such structures can serve to modulate DNA CT chemistry. The sensitivity of DNA CT to base pair stacking also provides the basis for the design of new DNA diagnostics, tools to detect mutations in DNA and to probe protein-DNA interactions. 

DNA-mediated charge transport has been a hot topic in chemistry for the last decade. Studies of DNA-mediated guanine radical cation (hole) transport are often focused on the efficiency of the transport between two guanines separated by a large distance, through the /r-stack of DNA base pairs [1-14]. The efficiency of the hole transport could be easily determined if one knew the distance between the hole donor and acceptor, the relative number of holes that reach the acceptor, and the time required for the transport. 

The DNA double helix is stabilized by hydrophobic interactions resulbng from the individual base pairs stacking on top of each other in the nonpolar interior of the double helix (Figs. 4-1 and 4-2). The hydrogen bonds, like the hydrogen bonds of proteins, contribute somewhat to the overall stability of the double helix but contribute greatly to the specificity for forming the correct base pairs. An incorrect base pair would not... 

Such activity enhancement can be ascribed to planarity of the naphthalene nucleus and its disposition for n-n stacking between the DNA base pairs. There is no literature precedence for involvement of naphthalene in such processes unless it is % electron deficient.211,212 However, our results suggest that both alkylated and acylated naphthalenes are intercalators with bacterial DNA. 

Figure 26. Schematic of the mediation of ET by a jt-stack of aromatic rings, such as the base pairs of duplex DNA. The D and A groups associated with the DNA molecule may be covalently linked to the helix, they may be intercalators, or they may be DNA base pairs.

While the structure of clusters responds to directionally specific electrostatic interactions, their stabilization energy reflects also the intervention of less specific dispersion interactions. This is, e.g., the case for stacked DNA base pairs. Stability of these pairs stems from dispersion energy while their structure is determined by dipole-dipole electrostatic interactions. Dispersion energy plays an important role in stabilizing clusters of biomacromolecules, where it may be the dominant attractive term. 

After briefly presenting some important milestones of MP2//HF studies in the quantum chemistry description of DNA base pairs, we turn to a more extensive discussion of DPT results for extended DNA-base aggregates, including model stacks and real molecular fragments. 

A. Hesselmann, G. Jansen, M. Schtitz, Interaction energy contributions of H-bonded and stacked structures of the AT and GC DNA base pairs from the combined density functional theory and intermolecular perturbation theory approach. J. Am. Chem. Soc. 128,11730-11731 (2006)... 

I. Nature of stacking interactions between intercalators (ethidium, daunomycin, ellipticine, and 4,6-Diaminide-2-phenylindole) and DNA base pairs. Ab initio quantum chemical, density functional theory, and empirical potential study. J. Am. Chem. Soc. 124, 3366-3376 (2002)... 

The CD induced in the visible absorption bands of proflavine cation intercalated to DMA was characterized in terms of the dye-DNA base pair exciton interactions [84]. In this work, the data were obtained at very low amounts of intercalated solute relative to the amount of oligonucleotide, with the goal of observing the CD spectra of isolated and monomeric dye systems. Substantial ionic strength effects were noted, indicating the electrostatic nature of the interaction. Comparison of the data with the results obtained after theoretical modeling indicated that the proflavine molecules insert in the DNA helix with the molecular plane parallel to the stacking plane of the DNA base pairs. 

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