Long-range Charge Transport Research Articles

Influence of intervening mismatches on long-range guanine oxidation in DNA duplexes.

A systematic investigation of the efficiency of oxidative damage at guanine residues through long-range charge transport was carried out as a function of intervening base mismatches. A series of DNA oligonucleotides were synthesized that incorporate a ruthenium intercalator linked covalently to the 5' terminus of one strand and containing two 5'-GG-3' sites in the complementary strand. Single base mismatches were introduced between the two guanine doublet steps, and the efficiency of transport through the mismatches was determined through measurements of the ratio of oxidative damage at the guanine doublets distal versus proximal to the intercalated ruthenium oxidant. Differing relative extents of guanine oxidation were observed for the different mismatches. The damage ratio of oxidation at the distal versus proximal site for the duplexes containing different mismatches varies in the order GC approximately GG approximately GT approximately GA > AA > CC approximately TT approximately CA approximately CT. For all assemblies, damage found with the Delta-Ru diastereomer was found to be greater than with the Lambda-diastereomer. The extent of distal/proximal guanine oxidation in different mismatch-containing duplexes was compared with the helical stability of the duplexes, electrochemical data for intercalator reduction on different mismatch-containing DNA films, and base-pair lifetimes for oligomers containing the different mismatches derived from 1H NMR measurements of the imino proton exchange rates. While a clear correlation is evident both with helix stability and electrochemical data monitoring reduction of an intercalator through DNA films, damage ratios correlate most closely with base-pair lifetimes. Competitive hole trapping at the mismatch site does not appear to be a key factor governing the efficiency of transport through the mismatch. These results underscore the importance of base dynamics in modulating long-range charge transport through the DNA base-pair stack.

Long-Range Oxidative Damage in DNA/RNA Duplexes

Oxidative damage as a result of DNA-mediated long-range charge transport occurs readily and at high yield in duplex DNA, and it is of interest whether similar damage can occur in duplex oligonucleotides that include both ribo- and deoxyribonucleotides. Assemblies containing RNA and mixed RNA.DNA strands were constructed containing tethered ethidium as a photooxidant. In photooxidation experiments, long-range oxidative damage to the ribose-containing strand of the oligonucleotide duplexes was examined. Hole injection by photoexcited ethidium followed by radical migration to oxidatively susceptible guanines afforded significant damage on ribose-containing strands at long range ( approximately 35 A). This damage does not differ substantially in yield and location from that found in B-DNA duplexes. No oxidative damage was found upon photooxidation of DNA/RNA duplexes containing tethered metallointercalator, despite the ability of the rhodium complex to promote oxidative damage at a distance in DNA duplexes. This result is attributed to the poor coupling of the rhodium complex into the A-like RNA/DNA duplex. The ability for long-range charge transport to occur in double-stranded nucleic acids of different comformations is considered in light of modeling studies that show interstrand base-base overlap between the opposing, complementary strands that make up RNA/DNA hybrid duplexes. Thus, the possibility of long-range radical migration to effect oxidative damage or signaling may be considered also in the context of transcriptional events.

Robust charge transport in DNA double crossover assemblies

Background: Multiple-stranded DNA assemblies, encoded by sequence, have been constructed in an effort to self-assemble nanodevices of defined molecular architecture. Double-helical DNA has been probed also as a molecular medium for charge transport. Conductivity studies suggest that DNA displays semiconductor properties, whereas biochemical studies have shown that oxidative damage to B-DNA at the 5′-G of a 5′-GG-3′ doublet can occur by charge transport through DNA up to 20 nm from a photo-excited metallointercalator. The possible application of DNA assemblies, in particular double crossover (DX) molecules, in electrical nanodevices prompted the design of a DNA DX assembly with oxidatively sensitive guanine moieties and a tethered rhodium photo-oxidant strategically placed to probe charge transport.Results: DX assemblies support long-range charge transport selectively down the base stack bearing the intercalated photo-oxidant. Despite tight packing, no electron transfer (ET) crossover to the adjacent base stack is observed. Moreover, the base stack of a DX assembly is well-coupled and less susceptible than duplex DNA to stacking perturbations. Introducing a double mismatch along the path for charge transport entirely disrupts long-range ET in duplex DNA, but only marginally decreases it in the analogous stack within DX molecules.Conclusions: The path for charge transport in a DX DNA assembly is determined directly by base stacking. As a result, the two closely packed stacks within this assembly are electronically insulated from one another. Therefore, DX DNA assemblies may serve as robust, insulated conduits for charge transport in nanoscale devices.

Long-range guanine oxidation in DNA restriction fragments by a triplex-directed naphthalene diimide intercalator.

Naphthalene diimide (NDI), a powerful oxidant that binds avidly to DNA by intercalation, is seen to damage the 5' guanine of 5'-GG-3' sites by photoactivated charge transport through DNA. When covalently tethered to the center of a triplex-forming oligonucleotide and delivered by triplex formation within a pyrimidine.purine-pyrimidine motif to a specific site on a restriction fragment, NDI can photooxidize guanine over at least 25-38 bp in each direction from the site of binding. Charge migration occurs in both directions from the NDI intercalator and on both DNA strands of the target, but the oxidation is significantly more efficient to the 3' side of the triplex. NDI and octahedral rhodium intercalators, when tethered directly to the 5' terminus of the triplex-forming strand as opposed to the center, generate significant amounts of oxidative damage only in the immediate vicinity of the intercalation site. Given that long-range charge transport depends on DNA stacking, these results suggest that the base stack is distorted at the 5' end of the triplex region in the duplex-triplex junction. Targeting of photooxidative damage by triplex formation extends our previous studies of long-range charge transport to significantly longer DNA sequences through a strategy that does not require covalent attachment of the photooxidant to the DNA being probed. Moreover, triplex targeting of oxidative damage provides for the first time a typical distance distribution for genomic charge transport of approximately 200 A around the oxidant.

Long-range charge transfer in DNA: transient structural distortions control the distance dependence.

Damage to DNA is often caused by oxidative reactions. In one such process, an electron is lost from a base, forming its radical cation. Further reaction of the radical cation can lead to permanent change, which results in mutation. This Account is a report on oxidative damage to DNA caused by irradiation of anthraquinone derivatives, which are either randomly bound to the DNA or attached to it covalently at specific locations. Radical cations introduced in the DNA by the excited quinone cause damage both near to it and far away. We describe a mechanism for long-range charge transport in DNA that depends on its spontaneous structural distortion, which we call phonon-assisted polaron hopping. This mechanism, and its extension, provides a framework for understanding the reactions and charge-transport properties of DNA.

16] Damage to DNA by long-range charge transport

Photochemical reactions on DNA assemblies containing tethered photooxidants, particularly metallointercalating photooxidants, have been critical in establishing that permanent damage to DNA bases can be generated as a result of radical migration from a remote site on the DNA duplex. Induction of a 1-electron deficiency in the oxidant attached covalently to the DNA remote from the oxidizable site leads to this “chemistry at a distance,” caused by efficient charge transport through the DNA base pair stack. Double helical DNA may be unique as a polymeric assembly in solution because of this interior core of stacked aromatic heterocyclic base pairs. Similarly stacked solid-state materials tend to be conducting along the stacking direction. This chapter describes the design and construction of DNA assemblies used to probe long-range oxidative damage in DNA. It also includes methodology for the oxidative repair of a thymine dimer lesion in DNA, as this “chemistry at a distance” also depends on long-range charge transfer through the DNA base pair stack.

Radical Cation Transport and Reaction in RNA/DNA Hybrid Duplexes: Effect of Global Structure on Reactivity

A series of anthraquinone-linked DNA and DNA/RNA hybrid duplexes was prepared and examined to assess the effect of global structure on long-range charge transport. Spectroscopic and chemical eviden...

Enhancing effect of amino acid residue models on the charge transfer in a Nafion® film incorporating Ru(bpy)32+ complex

An ITO electrode was coated by a Nafion® film incorporating Ru(bpy) 3 2+ complex as a redox center. An amino acid residue model compound, either 3-methylindole as a tryptophan model, 4-methylimidazole as a histidine model, or p-cresol as a tyrosine model, was dispersed in the polymer matrix to study its effect on the charge transport by the complex with a potential-step chronoamperospectrometry (PSCAS) method from 0 to 1.3 V (vs. SCE). The results showed that the model compound increased the fraction of the Ru(bpy) 3 2+ which was electroactive, and this was ascribed most probably to the mediation effect of the model molecule on the charge hopping between the redox centers. Assuming a random distribution of the complex and the model molecule in the polymer matrix, the charge transfer distance by hopping was estimated to be 1.6 nm in the absence of a mediator, but a long-range charge transport distance was 2.2 nm in the presence of 3-methylindole, 2.0 nm in the presence of 4-methylimidazole, and 2.3 nm in the presence of p-cresol.

DNA-mediated electron transfer: Chemistry at a distance

Abstract

Long-range oxidation of guanine by Ru(III) in duplex DNA

Background: Theoretical and experimental studies have demonstrated that 5′-GG-3′ sequences in DNA are ‘hot spots’ for oxidative damage, but few studies have definitively addressed whether oxidative damage to DNA may arise from a distance via long-range charge migration. Towards this end, we have prepared tethered ruthenium (Ru)-oligonucleotide duplexes and used a flash—quench strategy to demonstrate long-range charge transport through the DNA double helix. Results: DNA assemblies containing a tethered Ru(II) intercalator have been synthesized. Ru(III), generated in situ in the presence of externally bound electron-transfer quenchers, promotes base damage selectively at the 5′-G of a 5′-GG-3′ doublet located ∼ 37 Å from the binding site of the oxidant. In the absence of a guanine doublet, oxidative damage occurs equally at all guanine bases in the strand. Oxidative damage is also observed at long range for guanine in a G·A mismatch but not in a G·T mismatch. Conclusions: The present study expands the scope of long-range electron-transfer chemistry in terms of experiments, applications, and possible reactions within the cell. Here we demonstrate oxidative damage to DNA occurring with a high quantum yield over a distance of ∼37 Å using a ground-state oxidant. These results point to the equilibration of the radical across the DNA duplex to the sites of lowest energy. In addition, this charge migration is sensitive to the intervening π-stack formed by DNA base pairs and hence may be useful for the detection of mismatches.

Nonconductive long-range charge transport in hydrated biopolymers

Nonconductive long-range charge transport in hydrated biopolymers