A molecular dynamics calculations of hole transfer rates in DNA strands

A computational model, which includes both tunneling and thermal hopping mechanisms, has been applied to study the charge transfer in DNA (GC)n and (AT)n strands. The calculations revealed the crucial role played by the A or G NH2-group vibrations in the hole transfer in both types of strands. Charge-transfer rates in the two strands have been determined based on the molecular dynamics calculations. They are in good agreement with the available experimental data. The modeling approach used here may be employed in the theoretical study of the charge transfer in natural and artificial DNA strands containing AT and GC pairs.     

Cytosine-gated hole creation and transfer in DNA in aqueous solution

The selenite radical, SeO3-, has been found to selectively produce the cytosyl radical upon one-electron oxidation of duplex DNA. This is at first a surprising result as SeO3- can only oxidize guanine of the DNA bases, implying that the transiently formed guanyl radical cation must transpose into the neutral cytosyl radical with loss of a proton. Back oxidation to produce the neutral guanyl radical, in competition with another fixation reaction, is observed.     

Hole transfer in DNA: DNA as a scaffold for hole transfer between two organic molecules

Hole transfer process in ODNs conjugated with two organic molecules, pyrene (Py) and phenothiazine (Ptz) was investigated with the pulse radiolysis measurements. Monitoring the transient absorption of Py⁺ and Ptz⁺, it was shown that the hole transfer rate was dependent on the distance and sequence between Py and Ptz.     

Influence of solvent on the energetics of hole transfer in DNA

We have investigated the contribution of molecular environment to the exchange reactions in the DNA molecule taking into account different geometries of the reaction centers in oxidized and reduced states. We have observed the influence of the ionization potential of the donor and the acceptor on the free energy of the hole transfer reaction in the solvated DNA molecule: A decrease of the free energy occurs if IPA > or = IPD and an increase if IPA < or = IPD. The corresponding decrease of the potential barrier by 0.244 eV for hole migration from (G-C) to (A-T) and increase for migration from (G-C) to (G-C)n in solvent have been determined. The prevalence of oxidation of the redox states in the molecule center in comparison to the molecule sides due to the nonuniform charge distribution along the phosphate backbone was found to be stronger for the non-neutralized backbone than for the neutralized case. The influence of the single counterion on the electrostatic interactions within the solute DNA molecule has been found to be smoothly spread over a long distance approximately 7-8 base pairs. Therefore, each counterion contributes to the oxidation potential of the 7-8 nearest nucleosides and any irregularity due to phosphate neutralization would not significantly modify the potential profile for the hole migration through the DNA molecule.     

Kinetics of weak distance-dependent hole transfer in DNA by adenine-hopping mechanism

The kinetics of hole transfer in DNA by adenine-hopping mechanism was investigated by the combined pulse radiolysis-laser flash photolysis method. The hole transfer from Ptz*+* to oxG across the (A)n-bridge preceded by the A-hopping mechanism and the weak distance-dependent hole transfer with the rates faster than 108 s-1 over the distance range of 7-22 A was demonstrated. In contrast, hole transfer from oxG*+ to Ptz followed the single-step super exchange mechanism. Thus, two different processes for the hole transfer across the identical (A)n-bridge in DNA have been demonstrated. The results clearly show that the mechanism of hole transfer in DNA strongly depends on the redox nature of the oxidant, whether it produces only G*+ or both A*+ and G*+.     

Mechanism of charge separation in DNA by hole transfer through consecutive adenines

To investigate the mechanism of charge separation in DNA with consecutive adenines adjacent to a photosensitizer (Sens), a series of naphthalimide (NI) and 5-bromouracil ((br)U)-modified DNAs were prepared, and the quantum yields of formation of the charge-separated states (Phi) upon photo-excitation of the Sens NI in DNA were measured. The Phi was modulated by the incorporation site of (br)U, which changes the oxidation potential of its complementary A through hydrogen bonding and the hole-transfer rates between adenines. The results were interpreted as charge separation by means of the initial charge transfer between NI in the singlet excited state and the second- and third-nearest adenine to the NI. In addition, the oxidation of the A nearest to NI leads to the rapid charge recombination within a contact ion pair. This suggests that the charge-separation process can be refined to maximize the Phi by putting a redox-inactive spacer base pair between a photosensitizer and an A-T stretch.     

CASSCF/CAS-PT2 study of hole transfer in stacked DNA nucleobases

CASSCF and CAS-PT2 calculations are performed for the ground and excited states of radical cations consisting of two and three nucleobases. The generalized Mulliken-Hush approach is employed for estimating electronic couplings for hole transfer in the pi-stacks. We compare the CASSCF results with data obtained within Koopmans' approximation. The calculations show that an excess charge in the ground and excited states in the systems is quite localized on a single base both at the CASSCF level and in Koopmans' picture. However, the CASSCF calculations point to a larger degree of localization and, in line with this, smaller transition dipole moments. The agreement between the CAS-PT2 corrected energy gaps and the values estimated with Koopmans' theorem is better, with the CAS-PT2 calculations giving somewhat smaller gaps. Overall, both factors result in smaller CASSCF/CAS-PT2 couplings, which are reduced by up to 40% of the couplings calculated using Koopmans' approximation. The tabulated data can be used as benchmark values for the electronic couplings of stacked nucleobases. For the base trimers, comparison of the results obtained within two- and three-state models show that the multistate treatment should be applied to derive reliable estimates. Finally, the superexchange approach to estimate the donor acceptor electronic coupling in the stacks GAG and GTG is considered.     

Long-lived charge-separated state leading to DNA damage through hole transfer

The hole transfer causes the long-lived charge-separated state in DNA during the photosensitized one-electron oxidation of DNA. The combination of the transient absorption measurement and DNA damage quantification by HPLC clearly demonstrated that the yield of the DNA damage correlates well with the lifetime of the charge-separated state.     

Hole transfer rates in A-form DNA/2'-OMeRNA hybrid

The hole transfer rates in the DNA/DNA B-form duplex and DNA/2'-OMeRNA A-form duplex were measured which occurred in the time range of approximately 100 micros. The hole transfer rates in the A-form duplexes were slower and more strongly dependent on the temperature compared to those in the B-form duplexes, suggesting that the A-form is more rigid than the B-form duplex in this time scale.     

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.     

Theoretical rate constants of super-exchange hole transfer and thermally induced hopping in DNA

Recently, the electronic properties of DNA have been extensively studied, because its conductivity is important not only to the study of fundamental biological problems, but also in the development of molecular-sized electronics and biosensors. We have studied theoretically the reorganization energies, the activation energies, the electronic coupling matrix elements, and the rate constants of hole transfer in B-form double-helix DNA in water. To accommodate the effects of DNA nuclear motions, a subset of reaction coordinates for hole transfer was extracted from classical molecular dynamics (MD) trajectories of DNA in water and then used for ab initio quantum chemical calculations of electron coupling constants based on the generalized Mulliken-Hush model. A molecular mechanics (MM) method was used to determine the nuclear Franck-Condon factor. The rate constants for two types of mechanisms of hole transfer-the thermally induced hopping (TIH) and the super-exchange mechanisms-were determined based on Marcus theory. We found that the calculated matrix elements are strongly dependent on the conformations of the nucleobase pairs of hole-transferable DNA and extend over a wide range of values for the "rise" base-step parameter but cluster around a particular value for the "twist" parameter. The calculated activation energies are in good agreement with experimental results. Whereas the rate constant for the TIH mechanism is not dependent on the number of A-T nucleobase pairs that act as a bridge, the rate constant for the super-exchange process rapidly decreases when the length of the bridge increases. These characteristic trends in the calculated rate constants effectively reproduce those in the experimental data of Giese et al. [Nature 2001, 412, 318]. The calculated rate constants were also compared with the experimental results of Lewis et al. [Nature 2000, 406, 51].     

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.     

Electron transfer rates in DNA films as a function of tether length

A homologous series of DNA-modified electrodes has been investigated in which the molecular tether length varies. Using intercalated, covalently bound daunomycin as a redox probe, an exponential dependence of electron transfer rates on the number of intervening methylene groups in the sigma-bonded tether is observed. In contrast, variation in DM position within DNA yields no detectable change in rate. These data confirm that overall electron transfer rates in DNA films are limited by the tether, not the DNA.     

Investigation of excess-electron transfer in DNA double-duplex systems allows estimation of absolute excess-electron transfer and CPD cleavage rates

To investigate the parameters and rates that determine excess-electron transfer processes in DNA duplexes, we developed a DNA double-duplex system containing a reduced and deprotonated flavin donor at the junction of two duplexes with either the same or different electron acceptors in the individual duplex substructures. This model system allows us to bring the two electron acceptors in the duplex substructures into direct competition for injected electrons and this enables us to decipher how the kind of acceptor influences the transfer data. Measurements with the electron acceptors 8-bromo-dA (BrdA), 8-bromo-dG (BrdG), 5-bromo-dU (BrdU), and a cyclobutane pyrimidine dimer, which is a UV-induced DNA lesion, allowed us to obtain directly the maximum overall reaction rates of these acceptors and especially of the T=T dimer with the injected electrons in the duplex. In line with previous observations, we detected that the overall dimer cleavage rate is about one order of magnitude slower than the debromination of BrdU. Furthermore, we present a more detailed explanation of why sequence dependence cannot be observed when a T=T dimer is used as the acceptor and we estimate the absolute excess-electron hopping rates.     

DFT performance for the hole transfer parameters in DNA π stacks

Recently, we showed that unoccupied Kohn‐Sham (KS) orbitals stemming from DFT calculations of a neutral system can be used to derive accurate estimates of the free energy and electronic couplings for excess electron transfer in DNA (Félix and Voityuk, J Phys Chem A 2008, 112, 9043). In this article, we consider the propagation of radical cation states (hole transfer) through DNA π‐stacks and compare the performance of different exchange‐correlation functionals to estimate the hole transfer (HT) parameters. Two different approaches are used: (1) calculations that use occupied KS orbitals of neutral π stacks of nucleobases, and (2) the time‐dependent DFT method which is applied to the radical cation states of these stacks. Comparison of the calculated parameters with the reference data suggests that the best results are provided by the KS scheme with hybrid functionals (B3LYP, PBE0, and BH&HLYP). The TD DFT approach gives significantly less accurate values of the HT parameters. In agreement with high‐level ab initio results, the KS scheme predicts that the hole in π stacks is confined to a single nucleobase; in contrast, the spin‐unrestricted DFT method considerably overestimates the hole delocalization in the radical cations. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Pi stack structure and hole transfer couplings in DNA hairpins and DNA. A combined QM/MD study

Many key characteristics of hole transfer (HT) in DNA have been derived from spectroscopic studies of DNA hairpins. Because the capping groups in the hairpins can remarkably influence the structure and flexibility of the pi stack, and therefore, the charge transfer rate, the question arises of whether the HT parameters obtained for hairpins may be transferred to DNA oligomers. On the basis of large-time scale QM/MD simulations, we compare structural and electronic parameters of AT stacks in hairpins and DNA oligomers. We find that even in short hairpins, Sa-AA-Sd and Sa-AAA-Sd, the effects of the capping chromophores on the structure of the pi stack and the HT couplings properly averaged over MD trajectories are relatively small, and therefore, the hairpins are good models to study hole transfer through DNA. By contrast, the calculations of the electronic couplings based on the average structures of the systems lead to essential errors in the HT rate and the misleading statement that the charge transfer properties of DNA domains within hairpins are quite different from those of normal sequences.     

Computational model of hole transport in DNA

A computational model based on the molecular dynamics (MD) simulation for the hole transport in DNA has been developed and applied to study hole current in DNA strands consisting of different numbers of GC pairs. The approach is based on the hopping mechanism which is thermally activated. The calculations show that the hole hopping intensifies with the temperature and the transport rate increases in agreement with the experimental evidence. It is also determined that the degree of structural ordering in the DNA strand enhances the hole conductivity and reasons are provided why this may occur.