Reductive electron transfer and transport of excess electrons in DNA

In principle, DNA-mediated charge transfer processes can be categorized as either oxidative hole transfer or reductive electron transfer. In research on DNA damage, major efforts have focused on the investigation of oxidative hole transfer or transport, resulting in insights on the mechanisms. On the other hand, the transport or transfer of excess electrons has a large potential for biomedical applications, mainly for DNA chip technology. Yet the mechanistic details of this type of charge transfer chemistry were unclear. In the last two years this mechanism has been addressed in gamma-pulse radiolysis studies with randomly DNA-bound electron acceptors or traps. The major disadvantage of this experimental setup is that the electron injection and trapping is not site-selective. More recently, new photochemical assays for the chemical and spectroscopic investigation of reductive electron transfer and electron migration in DNA have been published which give new insights into these processes. Based on these results, an electron-hopping mechanism is proposed which involves pyrimidine radical anions as intermediate electron carriers.     

Investigation of the pathways of excess electron transfer in DNA with flavin-donor and oxetane-acceptor modified DNA hairpins

Oxetane is a potential intermediate that is enzymatically formed during the repair of (6-4) DNA lesions by special repair enzymes (6-4 DNA photolyases). These enzymes use a reduced and deprotonated flavin to cleave the oxetane by single electron donation. Herein we report synthesis of DNA hairpin model compounds containing a flavin as the hairpin head and two different oxetanes in the stem structure of the hairpin. The data show that the electron moves through the duplex even over distances of 17 A. Attempts to trap the moving electron with N2O showed no reduction of the cleavage efficiency showing that the electron moves through the duplex and not through solution. The electron transfer is sequence dependent. The efficiency is reduced by a factor of 2 in GC rich DNA hairpins.     

Electronic structures and long‐range electron transfer through DNA molecules

Quantum chemical calculation on an entire molecule of segments of native DNA was performed in an ab initio scheme with a simulated aqueous solution environment by overlapping dimer approximation and negative factor counting method. The hopping conductivity was worked out by random walk theory and compared with recent experiment. We conclude that electronic transport in native DNA molecules should be caused by hopping among different bases as well as phosphates and sugar rings. Bloch type transport through the delocalized molecular orbitals on the whole molecular system also takes part in the electronic transport, but should be much weaker than hopping. The complementary strand of the double helix could raise the hopping conductivity for more than 2 orders of magnitudes, while the phosphate and sugar ring backbone could increase the hopping conductivity through the base stacks for about 1 order of magnitude. DNA could transport electrons easily through the base stacks of its double helix but not its single strand. Therefore, the dominate factor that influences the electronic transfer through DNA molecules is the π stack itself instead of the backbone. The final conclusion is that DNA can function as a molecular wire in its double helix form with the conditions that it should be doped, the transfer should be a multistep hopping process, and the time period of the transfer should be comparable with that of an elementary chemical reaction. © 2000 John Wiley & Sons, Inc. Int J Quant Chem 78: 112–130, 2000     

Kinetic studies on the single electron transfer reaction between 2, 2, 6, 6-tetramethylpiperidine oxoammonium ions and phenothiazines: the application of Marcus theory

Electron transfer reactions take place readily between 2, 2, 6, 6-tetramethylpiperidine oxoammonium ions (1a, 1b) and phenothiazines (2a—2g), giving corresponding nitroxides (3a, 3b) and phenothiazine radical cations (4a—4g). The rate constants for the electron self-exchange reactions between 1 and 3, as well as between 2 and 4, are determined by EPR and ~1H NMR line-broadening effect in acetonitrile. By application of the Marcus theory, the kinetics of the cross-exchange reactions between 1 and 2 is studied.     

生物体系中电子转移机理的研究Ⅱ: 分子间电子转移及 电子供、受体间不同基 团的影响

利用自编程序MOPAC-ET中AM1方法,及KT(Koopman'sTheorem)法,研究了二苯负离子体系的分子间电子转移现象,计算了其电子供、受体在不同距离下的V~A~B及它们之间的相关性,另外,还对两苯环间不同介入基团对电子转移的影响做了初步研究,发现不同的介入基团存在着较大的差异。     

RNA is more UV resistant than DNA: the formation of UV-induced DNA lesions is strongly sequence and conformation dependent

DNA and RNA hairpins, which represent well-folded oligonucleotide structures, were irradiated and the amount of damaged hairpins was directly quantified by using ion-exchange HPLC. The types of photoproducts formed in the hairpins were determined by ESI-HPLC-MS/MS experiments. Irradiation of hairpins with systematically varied sequences and conformations (A versus B) revealed remarkable differences regarding the amount of photolesions formed. UV-damage formation is, therefore, a strongly sequence and conformation dependent process.     

Electron transfer in the photochemical reactions of phenothiazine with halomethanes

Photochemical transformations of phenothiazine (PTA) in solutions of halomethanes CH_nX_4–n (X = Cl, Br; n = 0, 1, 2) and in n-hexane—CH_nX_4–n mixtures under the irradiation with = 337 and 365 nm were studied. The rate constants of quenching of PTA fluorescence with halomethanes (k _q) are 4·10⁵—1.3·10¹⁰ L mol^–1 s^–1. The process occurs due to electron transfer with the C—X bond cleavage in the radical anion fragment of the primary radical ion pair. This results in the formation of the stable radical cation salt (PTA^·+X^–). The plot of k _q vs. free energy of electron transfer corresponds to the Rehm—Weller empirical equation for a one-electron process and is satisfactorily described in terms of the theory of nonradiative electron transitions in the approximation of one quantum vibration.     

Theoretical study on electron transfer in biological systems (III)

Iritramolwular electron transfer of nlctal-containing spiro π-electron system was studied by AM1 method in the MOPAC-ET program developed by the present group. The results indicated that with the increasing of the outer electric field F, the activation energy of the reaction decreased. When F reaches a certain threshold value, the activation energy barrirr becomcs zero and the rate of reaction achieves the largest value. The results also indicated that electron transfer matrix elements V_AB and reorganization energy λ were not obviously affected by outer electric field while the exothermicity ΔE was directly proportional to it.     

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.