Investigation of Excess-Electron Transfer in DNA Double-Duplex Systems Allows Estimation of Absolute Excess-Electron Transfer and CPD Cleavage Rates (original) (raw)
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Effects of Duplex Stability on Charge-Transfer Efficiency within DNA
Topics in Current Chemistry, 2004
In the first part of the chapter, emphasis is placed on the description of the main reactions of radical cations of the four predominant DNA purine and pyrimidine bases and minor 5-methylcytosine in aerated aqueous solutions. Information is also provided on the final one-electron oxidation products of 8-oxo-7,8-dihydroguanine, an ubiquitous decomposition product of DNA with most chemical and physical oxidizing agents, that exhibits a low ionization potential, and is therefore an excellent sink for positive hole migration within double-stranded DNA. In the second part of the review, it is shown that duplex stability plays a major role in the redistribution of positive holes generated by high intensity UV laser pulses on purine and pyrimidine bases towards guanine residues. These results were obtained by measurement of several oxidized nucleosides within DNA using a sensitive and accurate high performance liquid chromatography-tandem mass spectrometry assay.
Electron interaction with a DNA duplex: dCpdC:dGpdG
Physical chemistry chemical physics : PCCP, 2016
Electron attachment to double-stranded cytosine-rich DNA, dCpdC:dGpdG, has been studied by density functional theory. This system represents a minimal descriptive unit of a cytosine-rich double-stranded DNA helix. A significant electron affinity for the formation of a cytosine-centered radical anion is revealed to be about 2.2 eV. The excess electron may reside on the nucleobase at the 5' position (dC˙(-)pdC:dGpdG) or at the 3' position (dCpdC˙(-):dGpdG). The inter-strand proton transfer between the radical anion centered cytosine (N3) and the paired guanine (HN1) results in the formation of radical anion center separated complexes dC1H˙pdC:dG2-H(-)pdG and dCpdC2H˙:dGpdG1-H(-). These distonic radical anions are found to be approximately 1 to 4 kcal mol(-1) more stable than the normal radical anions. Intra-strand cytosine π → π transition energies are below the electron detachment energy. Inter-strand π → π transitions of the excess electron from C to G are predicted to be le...
DNA Electron Transfer Processes: Some Theoretical Notions
Charge motion within DNA stacks, probed by measurements of electric conductivity and by time-resolved and steady-state damage yield measurements, is determined by a complex mixture of electronic effects, coupling to quantum and classical degrees of freedom of the atomic motions in the bath, and the effects of static and dynamic disorder. The resulting phenomena are complex, and probably cannot be understood using a single integrated modeling viewpoint. We discuss aspects of the electronic structure and overlap among base pairs, the viability of simple electronic structure models including tight-binding band pictures, and the Condon approximation for electronic mixing. We also discuss the general effects of disorder and environmental coupling, resulting in motion that can span from the coherent regime through superexchange-type hopping to diffusion and gated transport. Comparison with experiment can be used to develop an effective phenomenological multiple-site hopping/superexchange model, but the microscopic understanding of the actual behaviors is not yet complete.
Angewandte Chemie International Edition, 2006
Numerous studies of the long-distance hole-migration process through a DNA double strand have revealed detailed insight into the distance and sequence dependence of charge-movement processes. In contrast to the wealth of information now available on the long-distance hole transfer, less is known about the complementary excess-electron-transfer process in which an anion, instead of a cation, moves through the duplex. We, and others, have recently shown that excess electrons move through DNA by a hopping-type mechanism in which the pyrimidine bases dT and dC act as stepping stones. Although the hopping of excess electrons through DNA is now a generally accepted model, conflicting data on the sequence dependence of this process were reported. The charge-transfer process was investigated by using DNA that was modified with either arylamines, pyrenes, or phenothiazines as the electron donor, or 5-bromouracil as the electron acceptor. It was shown that GC base pairs, in contrast to AT base pairs, reduce the efficiency of the excess-electron transfer through the duplex. Our studies with a reduced flavin [**] We thank the Deutsche Forschungsgemeinschaft, the Volkswagen Foundation, and the EU Marie Curie training and mobility program , project number MRTN-CT-2003-505086 [CLUSTOXDNA], for financial support. S.B. thanks the Fonds der Chemischen Industrie for a predoctoral fellowship.
Journal of the American Chemical Society, 2012
Electron tunneling pathways in enzymes are critical to their catalytic efficiency. Through electron tunneling, photolyase, a photoenzyme, splits UV-induced cyclobutane pyrimidine dimer into two normal bases. Here, we report our systematic characterization and analyses of photo-initiated three electron transfer processes and cyclobutane ring splitting by following the entire dynamical evolution during enzymatic repair with femtosecond resolution. We observed the complete dynamics of the reactants, all intermediates and final products, and determined their reaction time scales. Using (deoxy)uracil and thymine as dimer substrates, we unambiguously determined the electron tunneling pathways for the forward electron transfer to initiate repair and for the final electron return to restore the active cofactor and complete the catalytic photocycle. Significantly, we found that the adenine moiety of the unusual bent flavin cofactor is essential to mediating all electron-transfer dynamics through a super-exchange mechanism, leading to a delicate balance of time scales. The cyclobutane ring splitting takes tens of picoseconds while electron-transfer dynamics all occur on a longer time scale. The active-site structural integrity, unique electron tunneling pathways and the critical role of adenine assure the synergy of these elementary steps in this complex photorepair machinery to achieve maximum repair efficiency which is close to unity. Finally, we used the Marcus electron-transfer theory to evaluate all three electron transfer processes and thus obtained their reaction driving forces (free energies), reorganization energies, and electronic coupling constants, concluding the forward and futile back electron transfer in the normal region and that the final electron return of the catalytic cycle is in the inverted region.
Nucleic Acids Research, 2001
Fluorescence resonance energy transfer (FRET) experiments have been performed to elucidate the structural features of oligonucleotide duplexes containing the pyrimidine(6-4)pyrimidone photoproduct, which is one of the major DNA lesions formed at dipyrimidine sites by UV light. Synthetic 32mer duplexes with and without the (6-4) photoproduct were prepared and fluorescein and tetramethylrhodamine were attached, as a donor and an acceptor, respectively, to the aminohexyl linker at the C5 position of thymine in each strand. Steadystate and time-resolved analyses revealed that both the FRET efficiency and the fluorescence lifetime of the duplex containing the (6-4) photoproduct were almost identical to those of the undamaged duplex, while marked differences were observed for a cisplatin-modified duplex, as a model of kinked DNA. Lifetime measurements of a series of duplexes containing the (6-4) photoproduct, in which the fluorescein position was changed systematically, revealed a small unwinding at the damage site, but did not suggest a kinked structure. These results indicate that formation of the (6-4) photoproduct induces only a small change in the DNA structure, in contrast to the large kink at the (6-4) photoproduct site reported in an NMR study.
Superexchange Mediated Charge Hopping in DNA †
The Journal of Physical Chemistry A, 2002
We explore the relationship between the electronic-nuclear level structure, the electronic couplings, and the dynamics of hole hopping transport in DNA. We utilized the electronic coupling matrix elements for hole transfer between nearest-neighbor nucleobases in DNA Rösch, N. J. Chem. Phys. 2001, 114, 5614] to evaluate intrastrand and interstrand superexchange electronic couplings, which determine hole hopping rates within the framework of a semiempirical quantum mechanical-kinetic model. Calculations of the exponential distance (R) dependence of the superexchange mediated intrastrand electronic couplings |V super | 2 ∝ exp(-R) between guanines (G) in "short" G + (T-A) n G (n j 3) duplexes result in ) 0.8-0.9 Å -1 . We interpret the experimental data on time-resolved hole transport in the presence of a site-specifically bound methyl transferase mutant in DNA [Wagenknecht, H.-A.; Rajski, S. R.; Pascally, M.; Stemp, E. D. A.; Barton, J. K. J. Am. Chem. Soc. 2001, 123, 4400] in terms of composite sequential, interstrand and intrastrand superexchange mediated, and direct interstrand hole hopping. This mechanism accounts for the rate determining step, for the weak duplex size dependence of the rate, and for the longrange charge transport induced by interstrand superexchange via short (T-A) bridges, containing a single mediating nucleobase. For hole transfer via longer (T-A) n (n J 3) bridges, the superexchange mechanism is replaced by the parallel mechanism of thermally induced hole hopping (TIH) via long (A) n chains. A kinetic analysis of the experimental data for hole transport through seven GG pairs separated by (T-A) n (n ) 2-5) bridges across the 3′-5′ strand of the DNA duplex Schuster, G. B. J. Phys. Chem. B, 2001, 105, 11057] reveals that the superexchange-TIH crossover occurs at n ) n x ) 3. The explorations of the range of applicability and the breakdown of the superexchange mechanism in DNA lay the foundations for the scrutiny of the universality and system specificity of this mechanism in large-scale chemical and biophysical systems.
Chemphyschem, 2004
5-(Pyren-1-yl)-2′-deoxyuridine (PydU) and 5-(Pyren-1-yl)-2′-deoxycytidine (PydC) were used as model nucleosides for DNA-mediated reductive electron transport (ET) in steady-state fluorescence and femtosecond time-resolved transient absorption spectroscopy studies. Excitation of the pyrene moiety in PydU and PydC leads to an intramolecular electron transfer that yields the pyrenyl radical cation and the corresponding pyrimidine radical anion (dU.− and dC.−. By comparing the excited state dynamics of PydC and PydU, we derived information about the energy difference between the two pyrimidine radical anion states. To determine the influence of protonation on the rates of photoinduced intramolecular ET, the spectroscopic investigations were performed in acetonitrile, MeCN, and in water at different pH values. The results show a significant difference in the basicity of the generated pyrimidine radical anions and imply an involvement of proton transfer during electron hopping in DNA. Our studies revealed that the radical anion dC.− is being protonated even in basic aqueous solution on a picosecond time scale (or faster). These results suggest that protonation of dC.− may also occur in DNA. In contrast, efficient ET in PydU could only be observed at low pH values (<5). In conclusion, we propose—based on the free energy differences and the different basicities—that only dT.− but not dC.− can participate as an intermediate charge carrier for excess electron migration in DNA.