Base stacking, of DNA

Figure 12.16), can insert between the stacked base pairs of DNA. The bases are forced apart to accommodate these so-called intercalating agents, causing an unwinding of the helix to a more ladderlike structure. The deoxyribose-phosphate backbone is almost fully extended as successive base pairs are displaced 0.7 nm from one another, and the rotational angle about the helix axis between adjacent base pairs is reduced from 36° to 10°. 

Unlike solid state -stacks, however, double helical DNA is a molecular structure. Here CT processes are considered in terms of electron or hole transfer and transport, rather than in terms of material conductivity. Moreover, the 7r-stack of DNA is constructed of four distinct bases and is therefore heterogeneous and generally non-periodic. This establishes differences in redox energetics and electronic coupling along the w-stack. The intimate association of DNA with the water and counterions of its environment further defines its structure and contributes to inhomogeneity along the mole-... 

In many investigations of CT, pendant redox probes interact with both bases of abase pair. However, studies of base-base charge transfer can differentiate between discrete intra- and interstrand reactions (Fig. 7). These investigations further attest to the critical role of base stacking in DNA-mediated CT. In B-DNA duplexes, stacking interactions are largely restricted to... 

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. 

Intercalators associate with dsDNA by insertion between the stacked base pairs of DNA [52], EtBr binds to dsDNA with little to no sequence specificity, with one dye molecule inserting for every 4-5 base pairs [53]. It also binds weakly via a non-intercalative binding mechanism only after the intercalative sites have been saturated [54], Propidium iodide (PRO) is structurally similar to ethidium bromide, and both dyes show a fluorescence enhancement of approximately 20-30 fold upon binding to dsDNA [41]. As well, their excitation maxima shift 30-40 nm upon binding due to the environment change associated with intercalation into the more rigid and hydrophobic interior of the double-stranded nucleic acid structure relative to aqueous solution [41]. 

An important issue in the nature of the excited states in stacks of DNA bases is whether or not the states extended over a number of the bases are neutral Frenkel excitons or if they carry some degree of charge transfer character (exciplex or excimer).3 [2-4] A purely excitonic model neglects configurations... 

Sponer J, Leszczynski J, Hobza P (1996) Hydrogen bonding and stacking of DNA bases a review of quantum-chemical ab initio studies, J Biomol Struct and Dynamics 14 117—135... 

Double helical DNA is a water-soluble polymer that contains an electronically well-coupled stack of aromatic heterocyclic base pairs. This review describes efforts in our laboratory to characterize electron-transfer reactions between transition metal complexes bound by intercalation within the 7r-stack of DNA. Much information is available concerning the structure, synthesis, and methods of characterization of this polymer. Also, research in our laboratories has been directed toward describing the photophysical and photochemical properties of metal complexes bound to DNA. Using these metal complexes to probe the DNA 7r-way, we are now in a position to ask Is DNA a molecular wire ... 

Vasiliskov VA, Prokopenko DV, Mirzabekov AD. Parallel multiplex thermodynamic analysis of coaxial base stacking in DNA duplexes by oligodeoxyribonucleotide microchips. Nucleic Acids Res. 2001 29 2303-2313. 

Intercalating Agents are compounds with fused eiromatic ring systems that can wedge (intercalate) between the stacked base pairs of DNA. Tliis disrupts the structure of the DNA so that the replicative enzymes have difficulty in synthesizing DNA past the "intercalated" sites. Anthracycline glycosides and Actinomycin D are intercalators used to treat a variety of cancers. 

Multi-drug regimens used to treat cancers (e.g., lymphomas) sometimes include the drug doxorubicin (adriamycin). It is a natural product with a complex multi-ring structure that intercalates or slips in between the stacked base pairs of DNA and inhibits replication and transcription. 

From Figure 4.2 it would appear that all the atoms of the base pairs lie in a plane and that the base pairs of DNA stack like a stack of dollar bills. Although this is a reasonable first approximation, closer inspection reveals many deviations [6-8]. For example, there is abundant crystallographic evidence that the global conformation of DNA is quite sensitive to environmental conditions such as humidity and salt concentrations Figure 4.3 shows three of these well-accepted... 

Table 15.2 Calculated electronic properties-IP, EA and band gap (all values in eV) of periodic and aperiodic DNA base stacks of different chain lengths, for minimal and double zeta basis sets.

DNA is composed of two antiparallel complementary strands, which build a double helix. Pairing of the bases, which grant stability to the helix, takes place via hydrogen bonds. The base pairs (bp) are A-T (two bonds) and G-C (three bonds), and constitute the inner side of the double helix (Scheme 1). The backbone of the helix is composed of the sugar-phosphate chain. Another important contribution to the stability of the helix comes from the base stacking of the aromatic rings of the... 

Sponer J, Sponer JE, Mladek A, Jurecka P, Bands P, Otyepka M (2013) Nature and magnitude of aromatic base stacking in DNA and RNA Quantum chemistry, molecular mechanics, and experiment. Biopolym, 99, 978-988. 

Sponer, ]., Kypr, ]. (1993). Theoretical analysis of the base stacking in DNA choice of the force field and a comparison with the oligonucleotide crystal structures. Journal of Biomolecular Structure Dynamics, 11, 111. 

The dispersion energy plays an important role in the stacking of DNA bases thus the HF ab initio method could not be applied to characterize the nature of base stacking. The first comprehensive ab initio characterization of base stacking was... 

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