Electron Transfer In DNA Research Articles

Direct measurement of electrical transport through DNA molecules.

Attempts to infer DNA electron transfer from fluorescence quenching measurements on DNA strands doped with donor and acceptor molecules have spurred intense debate over the question of whether or not this important biomolecule is able to conduct electrical charges. More recently, first electrical transport measurements on micrometre-long DNA 'ropes', and also on large numbers of DNA molecules in films, have indicated that DNA behaves as a good linear conductor. Here we present measurements of electrical transport through individual 10.4-nm-long, double-stranded poly(G)-poly(C) DNA molecules connected to two metal nanoelectrodes, that indicate, by contrast, large-bandgap semiconducting behaviour. We obtain nonlinear current-voltage curves that exhibit a voltage gap at low applied bias. This is observed in air as well as in vacuum down to cryogenic temperatures. The voltage dependence of the differential conductance exhibits a peak structure, which is suggestive of the charge carrier transport being mediated by the molecular energy bands of DNA.

Electron Spin Resonance Study of Electron Transfer Rates in DNA: Determination of the Tunneling Constant β for Single-Step Excess Electron Transfer

An investigation of electron transfer in DNA at low temperatures in an aqueous glassy medium is reported for a system in which electrons are generated by radiation and trapped on DNA. The transfer ...

Soliton-like Solutions and Electron Transfer in DNA.

We consider various mechanisms of long-range electron transfer in DNAwhich enable us to explain recent controversial experiments. We show thatcontinuous super-exchange theory can explain the values of electron rateconstants in short fragments of DNA. The soliton-type electron transfer inlong segments of DNA is also dealt with.

DNA repair: models for damage and mismatch recognition

Maintaining the integrity of the genome is critical for the survival of any organism. To achieve this, many families of enzymatic repair systems which recognize and repair DNA damage have evolved. Perhaps most intriguing about the workings of these repair systems is the actual damage recognition process. What are the chemical characteristics which are common to sites of nucleic acid damage that DNA repair proteins may exploit in targeting sites? Importantly, thermodynamic and kinetic principles, as much as structural factors, make damage sites distinct from the native DNA bases, and indeed, in many cases, these are the features which are believed to be exploited by repair enzymes. Current proposals for damage recognition may not fulfill all of the demands required of enzymatic repair systems given the sheer size of many genomes, and the efficiency with which the genome is screened for damage. Here we discuss current models for how DNA damage recognition may occur and the chemical characteristics, shared by damaged DNA sites, of which repair proteins may take advantage. These include recognition based upon the thermodynamic and kinetic instabilities associated with aberrant sites. Additionally, we describe how small changes in base pair structure can alter also the unique electronic properties of the DNA base pair π-stack. Further, we describe photophysical, electrochemical, and biochemical experiments in which mismatches and other local perturbations in structure are detected using DNA-mediated charge transport. Finally, we speculate as to how this DNA electron transfer chemistry might be exploited by repair enzymes in order to scan the genome for sites of damage.

Electronic Interactions between π-Stacked DNA Base Pairs and Diphenylacetylene-4,4‘-dicarboxamide in Hairpin DNA

The {pi}-stacked base pairs of B-form DNA provide a unique medium for the investigation of electron transfer. Most recent investigations of the dynamics of photoinduced electron transfer in DNA have employed probe chromophores that are {pi}-stacked with an adjacent base pair. The approach has been to use organic chromophores as linkers in hairpin-forming bis(oligo-nucleotide) conjugates. A hairpin structure in which the organic chromophore is approximately coplanar with the adjacent base pair is supported by spectroscopic studies, molecular modeling, and crystallography.

Protein-Modulated DNA Electron Transfer

Protein-Modulated DNA Electron Transfer

Naphthalenedicarboxamides as Fluorescent Probes of Inter- and Intramolecular Electron Transfer in Single Strand, Hairpin, and Duplex DNA

The 2,6-naphthalenedicarboxamide chromophore has been investigated as a fluorescent probe for DNA hairpin and duplex formation and DNA electron transfer. The high fluorescence quantum yield and long singlet lifetime of this chromophore make it an attractive candidate for these studies. The kinetics of intermolecular quenching of a naphthalenedicarboxamide by nucleosides is dependent upon the nucleoside oxidation potential and solvent. Bis(oligonucleotide) conjugates containing naphthalene linkers have been prepared by means of conventional phosphoramidite chemistry. The base-sequence dependence of the naphthalene fluorescence intensity and decay times in both single-strand and hairpin conjugates indicates that singlet naphthalene is quenched by neighboring dA more efficiently than by dT, in accord with an electron-transfer quenching mechanism. These data are analyzed by means of a three-state model which includes a nonemissive “dark” state. Duplexes formed between complementary naphthalene-linked oligonucleotides display naphthalene excimer emission. The base-sequence dependence of the excimer emission quantum yields indicates that the excimer is not quenched by neighboring dA but that distance-dependent electron-transfer quenching by dG may occur. Quenching serves to protect the naphthalene chromophore from photobleaching in both single strand and duplex structures.

Energetics and rate of electron transfer in DNA from base radical anions to electron-affinic intercalators in aqueous solution

The dependency of the rate of intramolecular electron transfer in DNA in aqueous solution on the free energy change (ΔG°) and distance (L) is determined by observing electron transfer from DNA base radical anions to a series of eight compounds which are randomly intercalated into the DNA. Electron transfer initiated in DNA is found to be activation energy-controlled with k=k° exp(constant/L), which is different from published studies on electron transfer between photodonor–acceptor complexes attached to DNA that invoke an electron tunnelling description.

Electron migration in DNA matrix: an electron transfer reaction

This paper brings an active and provocative area of current research. It describes the investigation of electron transfer (ET) chemistry in general and ET reactions results in DNA in particular. Two DNA intercalating molecules were used: Ethidium Bromide as the donor (D) and Methyl-Viologen as the acceptor (A), the former intercalated between DNA bases and the latter in its surface. Using the Perrin model and fluorescence quenching measurements the distance of electron migration, herein considered to be the linear spacing between donor and acceptor molecule along the DNA molecule, was obtained. A value of 22.6 (± 1.1) angstroms for the distance and a number of 6.6 base pairs between donor and acceptor were found. In current literature the values found were 26 angstroms and almost 8 base pairs. DNA electron transfer is considered to be mediated by through-space interactions between the p-electron-containing base pairs.

DNA-mediated electron transfer from a modified base to ethidium: π-stacking as a modulator of reactivity

Background: The DNA double helix is composed of an array of aromatic heterocyclic base pairs and, as a molecular π-stack, represents a novel system for studying long-range electron transfer. Because many base damage and repair processes result from electron-transfer reactions, the ability of DNA to mediate charge transport holds important biological implications. Seemingly contradictory conclusions have been drawn about electron transfer in DNA from the many different studies that have been carried out. These studies must be reconciled so that this phenomenon can be understood both at a fundamental level and in the context of biological systems. Results: The photoinduced oxidation of a modified base, 7-deazaguanine, has been examined as a function of distance, sequence, and base stacking in DNA duplexes covalently modified with ethidium. Over ethidium/deazaguanine separations of 6–27 Å, the photooxidation reaction proceeded on a subnanosecond time scale, and the quenching yield exhibited a shallow distance dependence. The efficiency of the reaction was highly sensitive to small changes in base composition. Moreover, the overall distance-dependence of the reaction is sensitive to sequence, despite the constancy of photoexcited ethidium as acceptor. Conclusions: The remarkable efficiency of deazaguanine photooxidation by intercalated ethidium over long distances provides new evidence for fast electron-transfer pathways through DNA. By varying sequence as well as reactant separation, this work provides the first experimental demonstration of the importance of reactant stacking in the modulation of long-range DNA-mediated electron transfer.

DNA-mediated electron transfer

Electron transfer in DNA has been investigated for decades, but recent experiments highlight our limited fundamental understanding of these processes. Modern electron transfer theory may help to address some of the open mechanistic issues. We summarize and analyze the results of recent experiments from a theoretical perspective. Future research directions are suggested that might help to establish the molecular mechanism(s) for long-range DNA electron transfer.

Electron transfer in DNA: covalent attachment of spectroscopically unique donor and acceptor complexes

The notion that DNA is capable of electron transfer (ET) has inspired several groups to investigate the nature of this intriguing process. While several factors modulate ET reaction rates, the distance dependence of ET in DNA is the focus of our current investigations. To this end we propose that several design criteria must be met to facilitate the collection of kinetic data corresponding to DNA-mediated ET reactions. These criteria include (1) covalent attachment of site-selective donor-acceptor pairs, (2) incorporation of donor-acceptor pairs that offer minimal structural perturbation of the DNA duplex, and (3) use of spectroscopically distinguishable donor and acceptor complexes that allow identification of kinetic intermediates.

Electron transfer mechanisms

The tunneling pathway framework description of protein electron transfer reactions has prompted a lively discussion of how structure and evolution influence electron transfer rates. Recent protein and model system experiments, performed in solution and in organized media, are providing answers. The molecular mechanisms of DNA electron transfer reactions are being probed as well with new theoretical and experimental strategies.

Electron Transfer through DNA in the Course of Radical-Induced Strand Cleavage.

No benefit from base stacking is observed for rates of electron transfer in DNA. This conclusion was drawn from experiments with a new DNA assay in which a radical cationic site, generated by strand cleavage, can be reduced by the guanine bases in the same DNA (the electron transfer is indicated by arrows in the diagram). The distance dependence of this electron transfer step is determined by the chemical yield of the reduction product.

Distance Dependence of Photoinduced Electron Transfer in DNA

An intercalator that was selectively introduced into a DNA helix (see schematic representation on the right) was utilized to observe electron transfer through the DNA π stack. A clear distance dependence between the donor and the acceptor was given for electron transfer in both the 3′ and 5′ directions of a DNA.

Distance Dependence of Photoinduced Electron Transfer in DNA

Distance Dependence of Photoinduced Electron Transfer in DNA

Electron migration in DNA matrix: an electron transfer reaction

This paper brings an active and provocative area of current research. It describes the investigation of electron transfer (ET) chemistry in general and ET reactions results in DNA in particular. Two DNA intercalating molecules were used: Ethidium Bromide as the donor (D) and Methyl-Viologen as the acceptor (A), the former intercalated between DNA bases and the latter in its surface. Using the Perrin model and fluorescence quenching measurements the distance of electron migration, herein considered to be the linear spacing between donor and acceptor molecule along the DNA molecule, was obtained. A value of 22.6 (± 1.1) angstroms for the distance and a number of 6.6 base pairs between donor and acceptor were found. In current literature the values found were 26 angstroms and almost 8 base pairs. DNA electron transfer is considered to be mediated by through-space interactions between the p-electron-containing base pairs.

Charge Transfer in DNA: A Controversy

Electron transfer over distances of more than 40 Å through a DNA double strand (see schematic representation on the right) still stimulates controversy about mechanism but seems to be proven experimentally. Biochemical processes such as repair of photodimer damage can be initiated by DNA electron transfer. The dependence of electron transport on how nearly perfect a DNA base stack is suggests that conductivity can be used to quantify stacking quality or to recognize a DNA single strand.

Charge Transfer through the DNA Base Stack

AbstractWhether the DNA base pair stack might serve as a medium for efficient, long‐range charge transfer has been debated almost since the first proposal of the double‐helical structure of DNA. The consequences of long‐range radical migration through DNA are important with respect to understanding carcinogenesis and mutagenesis. Double‐helical DNA has in its core a stacked array of aromatic heterocyclic base pairs, and this molecular π stack represents a unique system in which to explore the chemistry of electron transfer. We designed a family of metal complexes which bind to DNA by intercalative stacking within the helix; these metallointercalators may be usefully applied in probing DNA‐mediated electron transfer. Here we describe a range of electron transfer reactions we carried out which are mediated by the DNA base paired stack. In some cases, DNA serves as a bridge, and spectroscopic analyses permit us to probe how the π stack couples DNA‐bound donors and acceptors. These studies point to the sensitivity of coupling to DNA intercalation. However, if the DNA π stack effectively bridges donors and acceptors, the base‐pair stack itself might serve not only as a conduit for electron transfer in DNA, but also in reactions initiated from a remote position. We carried out a series of reactions involving oxidative damage to DNA arising from the remotely positioned oxidant on the helix. The implications of long‐range charge migration through DNA to effect damage are substantial. As in other DNA‐mediated charge transfers, these reactions are highly dependent on DNA intercalation and the integrity of the intervening base‐pair stack, but not on molecular distance. Furthermore, a physiologically important DNA lesion, the thymine dimers, can be reversed in a reaction initiated by electron transfer. This repair reaction can also be promoted from a distance as a result of long‐range charge migration through the DNA base pair stack.

DNA Is Not a Molecular Wire: Protein-like Electron-Transfer Predicted for an Extended π-Electron System

The earliest studies of electron-transfer proteins1 raised the question of whether or not π-electron residues might facilitate electron transport.2 Three recent long-range electron-transfer experiments utilizing DNA bridges revisit this provocative, yet unresolved, question.3,4,5 The distance dependence of electron transfer in DNA is not a matter of purely academic concern; it controls the mechanism of DNA damage and repair in cells and is being exploited in new molecular probes of DNA sequence. We present a theoretical analysis based upon very large scale self-consistent-field quantum calculation of all valence electrons (as many as ∼3300) in these three systems. This computation is the first performed on such large macromolecules and also the first to extract long-range electronic interactions at this level of theory. DNA electron transfer is found to be mediated by through-space interactions between the π-electron-containing base pairs, but the magnitude of the coupling facilitated by this channel drops rapidly with distance, as a consequence of the ∼3.4 Å noncovalent gap between base pairs. These predictions are in agreement with most of the experimental data. The rapid decay of electron-transfer rates with distance computed here suggests that biologically controlled DNA electron-transfer events, of importance in DNA repair,6 must function over relatively short range. Moreover, the predicted distance dependence of electron transfer in DNA is strikingly close to that found in proteins.