Hole Transfer In DNA Research Articles

Coherent Effects in Charge Transport in Molecular Wires: Toward a Unifying Picture of Long-Range Hole Transfer in DNA.

In the framework of a multistep mechanism in which environmental motion triggers comparatively faster elementary electron-transfer steps and stabilizes hole-transfer products, microscopic coherence is crucial for rationalizing the observed yield ratios of oxidative damage to DNA. Interference among probability amplitudes of indistinguishable electron-transfer paths is able to drastically change the final outcome of charge transport, even in DNA oligomers constituted by similar building blocks, and allows for reconciling apparently discordant experimental observations. Properly tailored DNA oligomers appear to be a promising workbench for studying tunneling in the presence of dissipation at the macroscopic level.

The Dynamics of Hole Transfer in DNA.

High-energy radiation and oxidizing agents can ionize DNA. One electron oxidation gives rise to a radical cation whose charge (hole) can migrate through DNA covering several hundreds of Å, eventually leading to irreversible oxidative damage and consequent disease. Understanding the thermodynamic, kinetic and chemical aspects of the hole transport in DNA is important not only for its biological consequences, but also for assessing the properties of DNA in redox sensing or labeling. Furthermore, due to hole migration, DNA could potentially play an important role in nanoelectronics, by acting as both a template and active component. Herein, we review our work on the dynamics of hole transfer in DNA carried out in the last decade. After retrieving the thermodynamic parameters needed to address the dynamics of hole transfer by voltammetric and spectroscopic experiments and quantum chemical computations, we develop a theoretical methodology which allows for a faithful interpretation of the kinetics of the hole transport in DNA and is also capable of taking into account sequence-specific effects.

Experimental and Theoretical Study of Deprotonation of DNA Adenine Cation Radical

Among all the DNA components, extremely redox-active guanine (G) and adenine (A) bases are subject to facile loss of an electron and form cation radicals (G+· and A+·) when exposed to irradiation or radical oxidants. The subsequent deprotonation of G+· and A+· can invoke DNA damage or interrupt hole transfer in DNA. However, compared with intensive reports for G+·, studies on the deprotonation of A+· are still limited at present. Herein, we investigate the deprotonation behavior of A+· by time-resolved laser flash photolysis. The deprotonation product of A(N6-H)· is observed and the deprotonation rate constant, (2.0±0.1) × 107 s−1, is obtained at room temperature. Further, the deprotonation rate constants of A+· are measured at temperatures varying from 280 K to 300 K, from which the activation energy for the N6-H deprotonation is determined to be (17.1±1.0) kJ/mol by Arrhenius equation. In addition, by incorporating the aqueous solvent effect, we perform density functional theory calculations for A+· deprotonation in free base and in duplex DNA. Together with experimental results, the deprotonation mechanisms of A+· in free base and in duplex DNA are revealed, which are of fundamental importance for understanding the oxidative DNA damage and designing DNA-based electrochemical devices.

Sequence-Dependent Photocurrent Generation through Long-Distance Excess-Electron Transfer in DNA.

Given its well-ordered continuous π stacking of nucleobases, DNA has been considered as a biomaterial for charge transfer in biosensors. For cathodic photocurrent generation resulting from hole transfer in DNA, sensitivity to DNA structure and base-pair stacking has been confirmed. However, such information has not been provided for anodic photocurrent generation resulting from excess-electron transfer in DNA. In the present study, we measured the anodic photocurrent of a DNA-modified Au electrode. Our results demonstrate long-distance excess-electron transfer in DNA, which is dominated by a hopping mechanism, and the photocurrent generation is sequence dependent.

Sequence‐Dependent Photocurrent Generation through Long‐Distance Excess‐Electron Transfer in DNA

AbstractGiven its well‐ordered continuous π stacking of nucleobases, DNA has been considered as a biomaterial for charge transfer in biosensors. For cathodic photocurrent generation resulting from hole transfer in DNA, sensitivity to DNA structure and base‐pair stacking has been confirmed. However, such information has not been provided for anodic photocurrent generation resulting from excess‐electron transfer in DNA. In the present study, we measured the anodic photocurrent of a DNA‐modified Au electrode. Our results demonstrate long‐distance excess‐electron transfer in DNA, which is dominated by a hopping mechanism, and the photocurrent generation is sequence dependent.

Length-independent transport rates in biomolecules by quantum mechanical unfurling.

Experiments on hole transfer in DNA between donor and acceptor moieties revealed transfer rates which are independent of the molecular bridge length (within experimental error). However, the physical origin of this intriguing observation is still unclear. The hopping model implies that the hole propagates in multiple steps along the bridge from one localized state to another, and therefore the longer the bridge, the slower the transfer. This can explain weak length-dependence but not a length-independent transfer rate. We show that the rigid molecular structure of a poly-A bridge supports single step transitions from a localized hole state to delocalized states, spread over the entire bridge. Since propagation to the bridge end is a single step process (termed quantum unfurling) the transfer rate becomes independent of the bridge length. This explanation is consistent with experimental results, and emphasizes the importance of structural order in charge transfer through bio-molecular systems.

Charge-transfer matrix elements by FMO-LCMO approach: Hole transfer in DNA with parameter tuned range-separated DFT

A scheme for computing charge-transfer matrix elements with the linear combination of fragment molecular orbitals and the ‘nonempirically tuned range-separated’ density functional is presented. It takes account of the self-consistent orbital relaxation induced by environmental Coulomb field and the exchange interaction in fragment pairs at low computational scaling along the system size. The accuracy was confirmed numerically on benchmark systems of imidazole and furane homo-dimer cations. Applications to hole transfers in DNA nucleobase pairs and in a π-stack adenine octomer highlight the effects of orbital relaxation.

Driving Force Dependence of Charge Separation and Recombination Processes in Dyads of Nucleotides and Strongly Electron-Donating Oligothiophenes

Charge transfer in DNA has attracted great attention of scientists because of its importance in biological processes. However, our knowledge on excess-electron transfer in DNA still remains limited in comparison to numerous studies of hole transfer in DNA. To clarify the dynamics of excess-electron transfer in DNA by photochemical techniques, new electron-donating photosensitizers should be developed. Herein, a terthiophene and two 3,4-ethylenedioxythiophene oligomers were used as photosensitizers in dyads including natural nucleobases as electron acceptors. The charge separation and recombination processes in the dyads were investigated by femtosecond laser flash photolysis, and the driving force dependence of these rate constants was discussed on the basis of the Marcus theory. From this study, the conformation effect on charge recombination process was found. We expect that 3,4-ethylenedioxythiophene oligomers are useful in investigation of excess-electron-transfer dynamics in DNA.

A hybrid approach to simulation of electron transfer in complex molecular systems

Electron transfer (ET) reactions in biomolecular systems represent an important class of processes at the interface of physics, chemistry and biology. The theoretical description of these reactions constitutes a huge challenge because extensive systems require a quantum-mechanical treatment and a broad range of time scales are involved. Thus, only small model systems may be investigated with the modern density functional theory techniques combined with non-adiabatic dynamics algorithms. On the other hand, model calculations based on Marcus's seminal theory describe the ET involving several assumptions that may not always be met. We review a multi-scale method that combines a non-adiabatic propagation scheme and a linear scaling quantum-chemical method with a molecular mechanics force field in such a way that an unbiased description of the dynamics of excess electron is achieved and the number of degrees of freedom is reduced effectively at the same time. ET reactions taking nanoseconds in systems with hundreds of quantum atoms can be simulated, bridging the gap between non-adiabatic ab initio simulations and model approaches such as the Marcus theory. A major recent application is hole transfer in DNA, which represents an archetypal ET reaction in a polarizable medium. Ongoing work focuses on hole transfer in proteins, peptides and organic semi-conductors.

Hole Transfer Kinetics of DNA

Not long after the discovery of the double-helical structure of DNA in 1952, researchers proposed that charge transfer along a one-dimensional π-array of nucleobases might be possible. At the end of the 1990s researchers discovered that a positive charge (a hole) generated in DNA migrates more than 200 Å along the structure, a discovery that ignited interest in the charge-transfer process in DNA. As a result, DNA became an interesting potential bottom-up material for constructing nanoelectronic sensors and devices because DNA can form various complex two-dimensional and three-dimensional structures, such as smiley faces and cubes. From the fundamental aspects of the hole transfer process, DNA is one of the most well-studied organic molecules with many reports on the synthesis of artificial nucleobase analogues. Thus, DNA offers a unique system to study how factors such as the HOMO energy and molecular flexibility affect hole transfer kinetics. Understanding the hole transfer mechanism requires a discussion of the hole transfer rate constants (kHT). This Account reviews the kHT values determined by our group and by Lewis and Wasielewski's group, obtained by a combination of the synthesis of modified DNA and time-resolved spectroscopy. DNA consists of G/C and A/T base pairs; the HOMO localizes on the purine bases G and A, and G has a lower oxidation potential and a higher energy HOMO. Typically, long-range hole transfer proceeded via sequential hole transfer between G/C's. The kinetics of this process in DNA sequences, including those with mismatches, is reproducible via kinetic modeling using the determined kHT for each hole transfer step between G/C's. We also determined the distance dependence parameter (β), which describes the steepness of the exponential decrease of kHT. Because of this value, >0.6 Å(-1) for hole transfer in DNA, DNA itself does not serve as a molecular wire. Interestingly, hole transfer proceeded exceptionally fast for some sequences in which G/C's are located close to each other, an observation that we cannot explain by a simple sequential hole transfer between G/C's but rather through hole delocalization over the nucleobases. To further investigate and refine the factors that affect kHT, we examined various artificial nucleobases. We clearly demonstrated that kHT depends strongly on the HOMO energy gap between the bases (ΔHOMO), and that kHT can be increased with decreasing ΔHOMO. We reduced ΔHOMO between the two type of base pairs by replacing adenines (A's) with deazaadenines ((z)A's) or diaminopurines (D's) and showed that the hole transfer rate through the G/C and A/T mix sequence increased by more than 3 orders of magnitude. We also investigated how DNA flexibility affects kHT. Locked nucleic acid (LNA) modification, which makes DNA more rigid, lowered kHT by more than 2 orders of magnitude. On the other hand, 5-Me-2'-deoxyzebularine (B) modification, which increases DNA flexibility, increased kHT by more than 1 order of magnitude. These new insights in hole transfer kinetics obtained from modified DNAs may aid in the design of new molecular-scale conducting materials.

A Theory of Hole Transfer in DNA

A theory, which was previously applied to electron transfer in DNA, is applied to hole transfer between a dye molecule and an electrode coupled through a DNA bridge, because the applicability to such hole transfer has not yet been studied. The results calculated using the theory are compared with the experimental results for the same system. The theory reproduces the dependence of the current between the dye molecule and the electrode on the length of DNA. However, the agreement with experimental results requires that the reorganization energy in the ground state of a dye molecule be larger than that employed in previous studies of electron transfer.

Hole and excess electron transfer dynamics in DNA

Charge transfer in DNA attracts substantial attention from researchers in a wide group of fields such as bioscience, nanotechnology and physical chemistry. It is well known that both positive and negative charges, which are holes and excess electrons, respectively, contribute to the charge transfer in DNA. In the case of hole transfer in DNA, detailed mechanisms and dynamical parameters have been estimated by means of time-resolved spectroscopic methods and product analysis. On the other hand, detailed dynamics of excess electron transfer have not been established yet, although several aspects have been revealed by the continuous efforts of various research groups. In the present Perspective, studies on the charge transfer dynamics in DNA are summarized.

Temperature dependence for the rate of hole transfer in DNA: Nonadiabatic regime

The positive charge transfer in DNA is investigated, using the first principle treatment of the electron-vibrational interaction. We show that rearrangements of atoms belonging to base pairs induced by charge transfer are essentially quantum mechanical in nature. Particularly at room temperature, around half of the rearrangements occur via quantum tunneling, while the other half takes place via thermally activated transitions. This effect reduces activation energies for charge transfer between both AT and GC pairs by a factor of two compared to their classical values. These behaviors are described within small polaron theory for the non-adiabatic charge transfer and compared to the experimental data and previous theoretical studies.

Direct Measurement of the Dynamics of Excess Electron Transfer through Consecutive Thymine Sequence in DNA

Charge transfer in DNA is an essential process in biological systems because of its close relation to DNA damage and repair. DNA is also an important material used in nanotechnology for wiring and constructing various nanomaterials. Although hole transfer in DNA has been investigated by various researchers and the dynamic properties of this process have been well established, the dynamics of a negative charge, that is, excess electron, in DNA have not been revealed until now. In the present paper, we directly measured the rate of excess electron transfer (EET) through a consecutive thymine (T) sequence in nicked-dumbbell DNAs conjugated with a tetrathiophene derivative (4T) as an electron donor and diphenylacetylene (DPA) as an electron acceptor at both ends. The selective excitation of 4T by a femtosecond laser pulse caused the excess electron injection into DNA, and led to EET in DNA by a consecutive T-hopping mechanism, which eventually formed the DPA radical anion (DPA(•-)). The rate constant for the process of EET through consecutive T was determined to be (4.4 ± 0.3) × 10(10) s(-1) from an analysis of the kinetic traces of the ΔO.D. during the laser flash photolysis. It should be emphasized that the EET rate constant for T-hopping is faster than the rate constants for oxidative hole transfers in DNA (10(4) to 10(10) s(-1) for A- and G-hopping).

Coarse-Grained Time-Dependent Density Functional Simulation of Charge Transfer in Complex Systems: Application to Hole Transfer in DNA

We present a coarse-grained tight-binding method based on density functional theory (DFT) for the simulation of charge transfer in complex materials. The charge-transfer parameters are computed using a fragment-orbital approach combined with the approximative DFT method self-consistent charge density functional tight binding (SCC-DFTB), which allows to follow the dynamics of excess charge along nanosecond MD trajectories, still accounting for the important impact of structural fluctuations and solvent effects. Since DFT suffers from the self-interaction error, which would lead to a delocalization of the hole charge over the entire system, we study the effect of an empirical self-interaction correction in detail. The wave function of the excess charge is propagated within the framework of time-dependent DFT, where the electron (hole) and the atomic system are propagated simultaneously according to the derived coupled equations of motion. In the case of DNA, the solvent polarization effects are a dominant factor affecting the hole transport. The hole charge polarizes the surrounding water, which in turn supports a localization of the hole charge--a water polaron is formed, extended dynamically over several nucleobases. As this polarization of water accompanies the migrating hole, the motion of hole is significantly slowed down due to the solvent reorganization energy involved. The estimated hopping rate between neighboring adenines in poly(A)-DNA is in the order of 100 ns(-1), and our simulations clearly show that the charge transfer occurs in a nonadiabatic fashion, due to the small average electronic coupling of around 0.06 eV.

Solvent Fluctuations Drive the Hole Transfer in DNA: A Mixed Quantum−Classical Study

We studied the hole transfer across adenine bridges in double-stranded DNA by means of a multiscale approach, propagating the hole in the framework of time-dependent DFT coupled to classical molecular dynamics simulation using a QM/MM scheme. The hole transfer in DNA is codetermined by the large fluctuations of site energies on the order of 0.4 eV, induced by the solvent degrees of freedom. These fluctuations lead to charge-transfer active conformations with large transfer efficiency, which are characterized by a favorable alignment of site energies along the DNA strand. This reduces the barrier for the hole transfer dramatically. Consequently, we find that a charge hopping mechanism is operative already for short bridges with fewer than four adenines, in contrast to the charge-transfer models assuming static DNA structures, where only tunneling occurs. The solvent fluctuations introduce a significant correlation between neighboring sites, enhancing the charge-transfer rate, while the fluctuation of electronic couplings has only a minor impact on the charge-transfer characteristics. Our results emphasize the importance of an accurate description of solvent effects as well as proper sampling, and it is suggested that charge transfer in DNA is gated by the dynamics of solvent.

Modeling hole transfer in DNA. II. Molecular basis of charge transport in the DNA chain

A theoretical multiconfigurational second-order perturbation method, CASPT2, has been employed to determine the binding energies and electronic couplings for all pairs of stacked canonical nucleobases in the standard conformation of the B-DNA. The existence and relevance of conical intersections mediating the hole transfer process has been shown in different systems in vacuo and, by using hybrid QM/MM techniques, in a more realistic biological environment, formed by a double helix of 18 oligomers of DNA surrounded by water molecules. The present results support, therefore, the cooperative micro-hopping mechanism proposed in a previous work for the migration of the hole between adjacent π-stacked 2′-deoxycytidine 5′-monophosphate (dCMP) or alternate 2′-deoxyadenosine 5′-monophosphate and dCMP oligonucleotides.

Importance of Protonation State of Guanine Radical Cation During Hole Transfer in DNA

Importance of Protonation State of Guanine Radical Cation During Hole Transfer in DNA

Combined density functional theory and Landauer approach for hole transfer in DNA along classical molecular dynamics trajectories

We investigate in detail the charge transport characteristics of DNA wires with various sequences and lengths in the presence of solvent. Our approach combines large-scale quantum/classical molecular dynamics (MD) simulations with transport calculations based on Landauer theory. The quantum mechanical transmission function of the wire is calculated along MD trajectories and thus encodes the influence of dynamical disorder arising from the environment (water, backbone, counterions) and from the internal base dynamics. We show that the correlated fluctuations of the base pair dynamics are crucial in determining the transport properties of the wire and that the effect of fluctuations can be quite different for sequences with low and high static disorders (differences in base ionization potentials). As a result, in structures with high static disorder as is the case of the studied Dickerson dodecamer, the weight of high-transmissive structures increases due to dynamical fluctuations and so does the calculated average transmission. Our analysis further supports the basic intuition of charge-transfer active conformations as proposed by Barton et al. [J. Am. Chem. Soc. 126, 11471 (2004)]. However, not DNA conformations with good stacking contacts leading to large interbase hopping values are necessarily the most important, but rather those where the average fluctuation of ionization potentials along the base stack is small. The reason behind this is that the ensemble of conformations leads to average electronic couplings, which are large enough for sufficient transmission. On the other hand, the alignment of onsite energies is the critical parameter which gates the charge transport.

Solvent Reorganization Energy of Hole Transfer in DNA

We present an application of a molecular-dynamics-based scheme to evaluate the solvent reorganization energy of hole transfer in DNA. The obtained parameters can be used for simulations of hole transfer in DNA by means of Marcus' theory. Also, we perform an analysis of the reorganization energies, including the case of transfer of a delocalized hole.