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Tracking Photoinduced Charge Separation in DNA: From Start to Finish
Abstract
The initial studies of the dynamics of photoinduced charge separation conducted in our laboratories 20 years ago found strongly distance-dependent rate constants over short distances but failed to detect intermediates in the transport of positive charge (holes). These observations were consistent with the single-step superexchange or tunneling mechanism that had been observed for numerous donor–bridge–acceptor systems at that time. Subsequent studies found weak distance dependence for hole transport over longer distances in DNA, characteristic of incoherent hopping of either localized or delocalized holes. The introduction of synthetic DNA capped hairpin constructs possessing hole donor and acceptor chromophores (or purine bases) at opposite ends of a base-pair domain made it possible to determine the time required for transit of charge from one chromophore to the other and, in some cases, to distinguish between the transit time and the much faster initial charge injection time. These studies eliminated conventional tunneling as a viable mechanism for charge transport in DNA except at very short donor–acceptor separations; however, they did not establish the presence or nature of intermediates in the charge separation process.
... Indeed, this reactivity is by far the most involved in oxidative DNA damage, initiated by reactive oxygen species (ROS) generated by normal cellular metabolism, or by exogenous sources such as ionizing or ultraviolet irradiation [1][2][3]. In the thirty years since the discovery of long-range charge transport in DNA, as reviewed by Barton and coworkers [4][5][6], a large body of experimental data have accumulated showing that the one-electron oxidation of DNA produces a hole that can migrate through the double helix with the final destination at the G sites [4][5][6][7][8][9][10]. Among the four common DNA bases (A, G, T, and C), G is the most readily oxidized to the G radical cation (G •+ ), which is also the putative initial intermediate in the oxidative DNA damage. ...
... It should be recalled that SO 4 •− reacts with all four nucleobases (G, C, A, and T) with rate constants that are close to diffusion-controlled rates [13], although the primary damage is localized at Gs, having the lowest reduction potential (cf. Section 1) [4][5][6][7][8][9][10]. ...
... •− ). Most of these species can react with DNA, and the nucleobase guanine with the lowest reduction potential is the dominant site for oxidation within DNA through the hole transfer [4][5][6][7][8][9][10]. Analytical protocols and, in particular, liquid chromatography-tandem mass spectrometry (LC-MS/MS) allow the identification of the DNA lesions with high-accuracy in cellular DNA after enzymatic digestion, as reviewed recently [92,93]. ...
The guanyl radical or neutral guanine radical G(-H)• results from the loss of a hydrogen atom (H•) or an electron/proton (e–/H+) couple from the guanine structures (G). The guanyl radical exists in two tautomeric forms. As the modes of formation of the two tautomers, their relationship and reactivity at the nucleoside level are subjects of intense research and are discussed in a holistic manner, including time-resolved spectroscopies, product studies, and relevant theoretical calculations. Particular attention is given to the one-electron oxidation of the GC pair and the complex mechanism of the deprotonation vs. hydration step of GC•+ pair. The role of the two G(-H)• tautomers in single- and double-stranded oligonucleotides and the G-quadruplex, the supramolecular arrangement that attracts interest for its biological consequences, are considered. The importance of biomarkers of guanine DNA damage is also addressed.
... The oxidation potential of adenine (A) is estimated to be 0.4 eV higher than guanine, while the pyrimidine moieties of cytosine and thymine (C,T) are oxidized at a potential higher than G (0.6-0.8 eV) [17]. Therefore, the G radical cation (G •+ ) is considered the putative initial intermediate in the oxidative DNA damage [17][18][19][20][21]. Furthermore, the formation of the Watson-Crick G:C and A:T pairs in chloroform solution ...
We examined the reaction of hydroxyl radicals (HO•) and sulfate radical anions (SO4•−), which is generated by ionizing radiation in aqueous solutions under anoxic conditions, with an alternating GC doubled-stranded oligodeoxynucleotide (ds-ODN), i.e., the palindromic 5′-d(GCGCGC)-3′. In particular, the optical spectra of the intermediate species and associated kinetic data in the range of ns to ms were obtained via pulse radiolysis. Computational studies by means of density functional theory (DFT) for structural and time-dependent DFT for spectroscopic features were performed on 5′-d(GCGC)-3′. Comprehensively, our results suggest the addition of HO• to the G:C pair moiety, affording the [8-HO-G:C]• detectable adduct. The previous reported spectra of one-electron oxidation of a variety of ds-ODN were assigned to [G(-H+):C]• after deprotonation. Regarding 5′-d(GCGCGC)-3′ ds-ODN, the spectrum at 800 ns has a completely different spectral shape and kinetic behavior. By means of calculations, we assigned the species to [G:C/C:G]•+, in which the electron hole is predicted to be delocalized on the two stacked base pairs. This transient species was further hydrated to afford the [8-HO-G:C]• detectable adduct. These remarkable findings suggest that the double-stranded alternating GC sequences allow for a new type of electron hole stabilization via delocalization over the whole sequence or part of it.
... NFX sensitized CPD formation was also inhibited, however, by a 3 -C, and was two-fold lower at TTTC, CTTC and GTTC than for acetone which could be due to charge transfer quenching of NFX from the G pairing to the 3 -C. Further complicating the interpretation of sequence effects is evidence that charge transfer quenching by G may also take place through A's (86,87), and that triplet-triplet energy transfer can occur over several base pairs (42). It is likely then that the sequence specific difference between NFX and acetone sensitization arise from a complex competition between static quenching and triplettriplet energy transfer that depends on the orientation and pi stacking geometry of the NFX relative to the dipyrimidine site. ...
Cyclobutane pyrimidine dimers (CPDs) are the major products of DNA produced by direct absorption of UV light, and result in C to T mutations linked to human skin cancers. Most recently a new pathway to CPDs in melanocytes has been discovered that has been proposed to arise from a chemisensitized pathway involving a triplet sensitizer that increases mutagenesis by increasing the percentage of C-containing CPDs. To investigate how triplet sensitization may differ from direct UV irradiation, CPD formation was quantified in a 129-mer DNA designed to contain all 64 possible NYYN sequences. CPD formation with UVB light varied about 2-fold between dipyrimidines and 12-fold with flanking sequence and was most frequent at YYYR and least frequent for GYYN sites in accord with a charge transfer quenching mechanism. In contrast, photosensitized CPD formation greatly favored TT over C-containing sites, more so for norfloxacin (NFX) than acetone, in accord with their differing triplet energies. While the sequence dependence for photosensitized TT CPD formation was similar to UVB light, there were significant differences, especially between NFX and acetone that could be largely explained by the ability of NFX to intercalate into DNA.
... 7-deazaguanosine (7dza) differs in structure from guanosine solely by the replacement of a nitrogen atom with a C-H group at position seven of the guanine moiety (Scheme 1). This minor substitution results in ∼25% reduction in the oxidation potential, from 1.24 V in guanosine to 0.95 V in 7dza, [16][17][18][19][20][21] which has enabled the use of 7dza as a molecular probe to investigate charge transfer dynamics in DNA. 20,22,23 To the best of our knowledge, however, the electronic relaxation mechanism of 7dza has not been investigated, precluding a direct comparison with the excited-state dynamics of other purine monomers. ...
Minor structural modifications to the DNA and RNA nucleobases have a significant effect on their excited state dynamics and electronic relaxation pathways. In this study, the excited state dynamics of 7-deazaguanosine and guanosine 5′-monophosphate are investigated in aqueous solution and in a mixture of methanol and water using femtosecond broadband transient absorption spectroscopy following excitation at 267 nm. The transient spectra are collected using photon densities that ensure no parasitic multiphoton-induced signal from solvated electrons. The data can be fit satisfactorily using a two- or three-component kinetic model. By analyzing the results from steady-state, time-resolved, computational calculations, and the methanol–water mixture, the following general relaxation mechanism is proposed for both molecules, Lb → La → ¹πσ*(ICT) → S0, where the ¹πσ*(ICT) stands for an intramolecular charge transfer excited singlet state with significant πσ* character. In general, longer lifetimes for internal conversion are obtained for 7-deazaguanosine compared to guanosine 5′-monophosphate. Internal conversion of the ¹πσ*(ICT) state to the ground state occurs on a similar time scale of a few picoseconds in both molecules. Collectively, the results demonstrate that substitution of a single nitrogen atom for a methine (C–H) group at position seven of the guanine moiety stabilizes the ¹ππ* Lb and La states and alters the topology of their potential energy surfaces in such a way that the relaxation dynamics in 7-deazaguanosine are slowed down compared to those in guanosine 5′-monophosphate but not for the internal conversion of ¹πσ*(ICT) state to the ground state.
... Herein, we demonstrate the utility of guaninium (G)derived low-dimensional perovskites in stabilizing the a-FAPbI 3 perovskite phase,w hich is assessed by solid-state NMR spectroscopy,X-ray crystallography,molecular dynamics simulations,a nd DFT calculations.G uanine is ab iologically relevant organic molecule that plays an important role in stabilizing the DNAs tructure (Figure 1a), while displaying the propensity for the formation of conductive supramolecular assemblies and functional materials. [18][19][20][21] We have therefore utilized its functional units to form an ovel hybrid perovskite structure based on the low dimensional G 2 PbI 4 composition, which was used to increase the performance and stability of a-FAPbI 3 perovskite solar cells. ...
Formamidinium (FA) lead iodide perovskite materials feature promising photovoltaic performances in conjunction with superior thermal stabilities. However, the conversion of the perovskite α‐FAPbI 3 phase to the thermodynamically stable yet photovoltaically inactive δ‐FAPbI3 phase compromises the photovoltaic performances of the corresponding solar cells. Herein, we demonstrate a novel strategy for overcoming this challenge by employing low‐dimensional hybrid perovskite materials comprising guaninium (G) organic spacer layers that act as stabilizers of the three‐dimensional α‐FAPbI3 phase. Furthermore, we unravel the underlying mode of interaction at the atomic level by means of solid‐state nuclear magnetic resonance spectroscopy in conjunction with X‐ray crystallography, transmission electron microscopy, molecular dynamics simulations and DFT calculations. As a result, we obtain low‐dimensional‐phase‐containing hybrid FAPbI3 perovskite solar cells with improved performances, which is accompanied by enhanced long‐term stability.
... Herein, we demonstrate the utility of guaninium (G)derived low-dimensional perovskites in stabilizing the a-FAPbI 3 perovskite phase,w hich is assessed by solid-state NMR spectroscopy,X-ray crystallography,molecular dynamics simulations,a nd DFT calculations.G uanine is ab iologically relevant organic molecule that plays an important role in stabilizing the DNAs tructure (Figure 1a), while displaying the propensity for the formation of conductive supramolecular assemblies and functional materials. [18][19][20][21] We have therefore utilized its functional units to form an ovel hybrid perovskite structure based on the low dimensional G 2 PbI 4 composition, which was used to increase the performance and stability of a-FAPbI 3 perovskite solar cells. ...
Formamidinium (FA) lead iodide perovskite materials feature promising photovoltaic performances and superior thermal stabilities. However, conversion of the perovskite α‐FAPbI3 phase to the thermodynamically stable yet photovoltaically inactive δ‐FAPbI3 phase compromises the photovoltaic performance. A strategy is presented to address this challenge by using low‐dimensional hybrid perovskite materials comprising guaninium (G) organic spacer layers that act as stabilizers of the three‐dimensional α‐FAPbI3 phase. The underlying mode of interaction at the atomic level is unraveled by means of solid‐state nuclear magnetic resonance spectroscopy, X‐ray crystallography, transmission electron microscopy, molecular dynamics simulations, and DFT calculations. Low‐dimensional‐phase‐containing hybrid FAPbI3 perovskite solar cells are obtained with improved performance and enhanced long‐term stability.
... 21 24,35,36 This suggests that dG •+ reduction by tyrosine within a NCP can compete with deprotonation and hole transfer. 36,37 Hole reduction in DNA by Tyr41 was initially probed by examining the effect of a deuterated buffer on HTE ( Figure S12, 13). We anticipated that reduction by Tyr41 would occur via proton coupled electron transfer (PCET) and would therefore be susceptible to a deuterium kinetic isotope effect (KIE). ...
Electron deficient "holes" migrate over long distances through the π-system in free DNA. Hole transfer efficiency (HTE) is strongly dependent on sequence and π-stacking. However, there is no consensus regarding the effects of nucleosome core particle (NCP) environment on hole migration. We quantitatively determined HTE in free DNA and NCPs by independently generating holes at specific positions in DNA. The relative HTE varied widely with respect to position within the NCP and proximity to tyrosine, which suppresses hole transfer. These data indicate that hole transfer in chromatin will be affected by the DNA sequence and its position with respect to histone proteins within NCPs.
Charge separation is one of the most common consequences of the absorption of UV light by DNA. Recently, it has been shown that this process can enable efficient self-repair of cyclobutane pyrimidine dimers (CPDs) in specific short DNA oligomers such as the GAT 00000000 00000000 00000000 00000000 11111111 00000000 11111111 00000000 00000000 00000000 T sequence. The mechanism was characterized as sequential electron transfer through the nucleobase stack which is controlled by the redox potentials of nucleobases and their sequence. Here, we demonstrate that the inverse sequence TTAG promotes self-repair with higher quantum yields (0.58 ± 0.23%) than GATT (0.44 ± 0.18%) in a comparative study involving UV-irradiation experiments. After extended exposure to UV irradiation, a photostationary equilibrium between self-repair and damage formation is reached at 33 ± 13% for GATT and at 40 ± 16% for TTAG, which corresponds to the maximum total yield of self-repair. Molecular dynamics and quantum mechanics/molecular mechanics (QM/MM) simulations allowed us to assign this disparity to better stacking overlap between the G and A bases, which lowers the energies of the key A⁻˙G⁺˙ charge transfer state in the dominant conformers of the TTAG tetramer. These conformational differences also hinder alternative photorelaxation pathways of the TTAG tetranucleotide, which otherwise compete with the sequential electron transfer mechanism responsible for CPD self-repair. Overall, we demonstrate that photoinduced electron transfer is strongly dependent on conformation and the availability of alternative photodeactivation mechanisms. This knowledge can be used in the identification and prediction of canonical and modified DNA sequences exhibiting efficient electron transfer. It also further contributes to our understanding of DNA self-repair and its potential role in the photochemical selection of the most photostable sequences on the early Earth.
Electron-rich 1,5-dialkoxynaphthalene (DAN) and electron-deficient 1,8,4,5-naphthalenetetracarboxylic diimide (NDI) are known to interact through the formation of charge-transfer complexes. The introduction of DAN and NDI into various DNA duplexes and hairpins was investigated by ultraviolet (UV) melting curve analysis. The positioning of the DAN:NDI pair was found to strongly influence the stability of DNA duplex and hairpins. In particular, while the introduction of one DAN/NDI pair in front of each other in the center of a DNA duplex led to a decrease of the thermal stability (ΔTm - 6 °C), the addition of a second pair restored or even increased the stability. In contrast, the introduction of DAN:NDI pairs at the end of a duplex always induced a strong stabilization (ΔTm up to +20 °C). Finally, a DAN:NDI pair positioned in the loop of a hairpin induced a stronger stabilization than a T4 loop (ΔTm + 10 °C). Based on charge-transfer interactions, the strong stabilizations observed allow the preparation of highly stabilized DNA nanostructures opening the way to numerous applications in nanotechnology.
Strongly-coupled multichromophoric assemblies orchestrate the absorption, transport, and conversion of photonic energy in natural and synthetic systems. Programming these functionalities involves the production of materials in which chromophore placement is precisely controlled. DNA nanomaterials have emerged as a programmable scaffold that introduces the control necessary to select desired excitonic properties. While the ability to control photophysical processes, such as energy transport, has been established, similar control over photochemical processes, such as interchromophore charge transfer, has not been demonstrated in DNA. In particular, charge transfer requires the presence of close-range interchromophoric interactions, which have a particularly steep distance dependence, but are required for eventual energy conversion. Here, we report a DNA-chromophore platform in which long-range excitonic couplings and short-range charge-transfer couplings can be tailored. Using combinatorial screening, we discovered chromophore geometries that enhance or suppress photochemistry. We combined spectroscopic and computational results to establish the presence of symmetry-breaking charge transfer in DNA-scaffolded squaraines, which had not been previously achieved in these chromophores. Our results demonstrate that the geometric control introduced through the DNA can access otherwise inaccessible processes and program the evolution of excitonic states of molecular chromophores, opening up opportunities for designer photoactive materials for light harvesting and computation.
Quantum dots (QDs)-based composites are promising candidates for optoelectronic and photonic devices. Understanding the photo-induced carrier dynamics is fundamental and crucial for improving the photoelectric conversion efficiency of nanocomposites. In this work, we have constructed nanocomposite hybridizing CdTe QDs with Au nanoclusters (Au NCs) and investigated the ultrafast carrier dynamics and enhanced photoelectric properties. The concurrent photoluminescence quenching and lifetime decreasing of CdTe QDs and Au NCs suggest a type-II band alignment, facilitating the carrier dynamics in the CdTe QDs-Au NCs' nanocomposite. The transient absorption measurements demonstrate an ultrafast and efficient electron transfer from CdTe QDs to Au NCs, effectively promoting the charge separation and inhibiting the exciton recombination. We found that the quantum efficiency of hot electron transfer can reach ∼50% with a rate constant of 1.01 × 10 ¹³ s ⁻¹ for the CdTe QDs-Au NCs' nanocomposite. As a result, the photocurrent performance of the CdTe QDs-Au NC device has been dramatically enhanced due to the efficient separation of photogenerated carriers, compared to that of individual CdTe QDs and Au NCs. These findings are significant for developing the light-harvesting and photoelectric devices based on semiconductor QDs and metal NCs.
This Communication describes the formation of 1D-coordination polymeric motifs involving modified flavin analog connected together through intervening silver ions. Rare bidentate coordination mode for model flavin was achieved with silver...
The flow of charge through molecules is central to the function of supramolecular machines, and charge transport in nucleic acids is implicated in molecular signaling and DNA repair. We examine the transport of electrons through nucleic acids to understand the interplay of resonant and nonresonant charge carrier transport mechanisms. This study reports STM break junction measurements of peptide nucleic acids (PNAs) with a G-block structure and contrasts the findings with previous results for DNA duplexes. The conductance of G-block PNA duplexes is much higher than that of the corresponding DNA duplexes of the same sequence; however, they do not display the strong even-odd dependence conductance oscillations found in G-block DNA. Theoretical analysis finds that the conductance oscillation magnitude in PNA is suppressed because of the increased level of electronic coupling interaction between G-blocks in PNA and the stronger PNA-electrode interaction compared to that in DNA duplexes. The strong interactions in the G-block PNA duplexes produce molecular conductances as high as 3% G0, where G0 is the quantum of conductance, for 5 nm duplexes.
The designing of tunable molecular systems that can host spin qubits is a promising strategy for advancing the development of quantum information science (QIS) applications. Photogenerated radical pairs are good spin qubit pair (SQP) candidates because they can be initialized in a pure quantum state that exhibits relatively long coherence times. DNA is a well-studied molecular system that allows for control of energetics and spatial specificity through careful design and thus serves as a tunable scaffold on which to control multispin interactions. Here, we examine a series of DNA hairpins that use naphthalenediimide (NDI) as the hairpin linker. Photoexcitation of the NDI leads to subnanosecond oxidation of guanine (G) within the duplex or a stilbenediether (Sd) end-cap to give NDI•--G•+ or NDI•--Sd•+ SQPs, respectively. A 2,2,6,6-tetramethylpiperdinyl-1-oxyl (TEMPO) stable radical is covalently attached to the hairpin at varying distances from the SQP spins. While TEMPO has a minimal effect on the SQP formation and decay dynamics, EPR spectroscopy indicates that there are significant spin-spin dipolar interactions between the SQP and TEMPO. We also demonstrate the ability to implement more complex spin manipulations of the NDI•--Sd•+-TEMPO system using pulse-EPR techniques, which is important for developing DNA hairpins for QIS applications.
The photochemical reaction of 4-nitroindole and guanosine was studied with the transient absorption spectroscopy as guanine is an effective hole trap during the charge transfer in DNA, and 4-nitroindole is a universal base. Excitation of 4-nitroindole generates the lowest triplet excited state 4-nitroindole (³HN-NO2) within 10 ns in the quantum yield 0.41. ³HN-NO2 has increased basicity compared to its ground state. Consequently, its nitro group exhibits the hydrogen bond accepting ability. ³HN-NO2 can interact with guanosine (G) to form the hydrogen-bonded ³HN-NO2…G complex with the rate constant k=(8.7 ± 0.3)×10⁹ M⁻¹⋅s⁻¹. The hydrogen-bonded complex is identified based on the blue shift evolvement of the absorption maximum of ³HN-NO2 in alcoholic solutions. The reduction potential of ³HN-NO2 is Ered(³HN-NO2) = 1.23 V vs. SCE. The electron transfer occurs in the ³HN-NO2…G complex and generates G+• and HN-NO2−• followed by the proton transfer from N1 and N2 of G producing radicals HN-NO2H•, G(N1-H)• and G(N2-H)•.
Experimental evidence suggests that DNA-mediated redox signaling between high-potential [Fe4S4] proteins is relevant to DNA replication and repair processes, and protein-mediated charge transfer (CT) between [Fe4S4] clusters and nucleic acids is a fundamental process of the signaling and repair mechanisms. We analyzed the dominant CT pathways in the base excision repair glycosylase MutY using molecular dynamics simulations and hole hopping pathway analysis. We find that the adenine nucleobase of the mismatched A·oxoG DNA base pair facilitates [Fe4S4]-DNA CT prior to adenine excision by MutY. We also find that the R153L mutation in MutY (linked to colorectal adenomatous polyposis) influences the dominant [Fe4S4]-DNA CT pathways and appreciably decreases their effective CT rates.
The chirality-induced spin selectivity (CISS), demonstrated in diverse chiral molecules by numerous experimental and theoretical groups, has been attracting extensive and ongoing interest in recent years. As the secondary structure of DNA, the charge transfer along DNA hairpins has been widely studied for more than two decades, finding that DNA hairpins exhibit spin-related effects as reported in recent experiments. Here, we propose a setup to demonstrate directly the CISS effect in DNA hairpins contacted by two nonmagnetic leads at both ends of the stem. Our results indicate that DNA hairpins present a pronounced CISS effect and the spin polarization could be enhanced by using conducting molecules as the loop. In particular, DNA hairpins exhibit several intriguing features. First, the local spin currents can flow circularly and assemble into a number of vortex clusters when the electron energy locates in the left/right electronic band of the stem. The chirality of vortex clusters in each band is the same and will be reversed by switching the electron energy from the left band to the right one, inducing the sign reversal of the spin polarization. Interestingly, the local spin currents can be greater than the corresponding spin component of the source-drain current. Second, both the conductance and the spin polarization can increase with molecular length as well as dephasing strength, contrary to the physical intuition that the transmission ability of molecular wires should be poorer when suffering from stronger scattering. Third, we unveil the optimal contact configuration of efficient electron transport and that of the CISS effect, which are distinct from each other and can be controlled by dephasing strength. The experimental realization of these results is discussed and the underlying physical mechanism is illustrated.
There has never been a time when colour did not fascinate humanity, inspiring an unceasing manufacturing of a kaleidoscopic variety of dyes and pigments that brought about great revolutions in art, cosmetics, fashion, and our lifestyle as a whole. Over the centuries these tints evolved from raw earths to molecular masterpieces devised by expert chemists whose properties are now being exploited far beyond traditional applications. Mimicking Nature, a timely challenge, regards the preparation of innovative and highly efficient multicoloured architectures structured at the molecular and nanoscopic scale with specific light-absorbing and light-emitting properties. This tutorial review provides an overview on the chemical strategies developed to engineer and customise these ingenious coloured nanostructures tackling the current performance of organic matter in cutting edge technological sectors, such as solar energy conversion. Key learning points Synthetic strategies tailoring colours in multichromophoric systems with tuneable absorptive and emissive properties. Strength and limitations of covalent and non-covalent bottom-up approaches for the synthesis of light-harvesting systems. Tailoring the photophysical properties of multichromophoric architectures: structure/property correlations.
The redox properties of two large DNA fragments composed of 39 base pairs, differing only by an 8-oxoguanine (8oxoG) defect replacing a guanine (G), were investigated in physiological conditions using mixed quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulations. The quantum region of the native fragment comprised 3 G-C base pairs, while one G was replaced by an 8oxoG in the defect fragment. The calculated values for the redox free energy are 6.55 ± 0.28 eV and 5.62 ± 0.30 eV for the native and the 8oxoG-containing fragment, respectively. The respective estimates for the reorganization free energy are 1.25 ± 0.18 eV and 1.00 ± 0.18 eV. Both reactions follow Marcus theory for electron transfer. The large difference in redox potential between the two fragments shows that replacement of a G by an 8oxoG renders the DNA more easily oxidizable. This finding is in agreement with the suggestion that DNA fragments containing an 8oxoG defect can act as sinks of oxidative damage that protect the rest of the genome from assault. In addition, the difference in redox potential between the native and the defect DNA fragment indicates that a charge transfer-based mechanism for the recognition of DNA defects might be feasible, in line with recent suggestions based on experimental observations.
Charge transfer and charge transport are by far among the most important processes for sustaining life on Earth and for making our modern ways of living possible. Involving multiple electron-transfer steps, photosynthesis and cellular respiration have been principally responsible for managing the energy flow in the biosphere of our planet since the Great Oxygen Event. It is impossible to imagine living organisms without charge transport mediated by ion channels, or electron and proton transfer mediated by redox enzymes. Concurrently, transfer and transport of electrons and holes drive the functionalities of electronic and photonic devices that are intricate for our lives. While fueling advances in engineering, charge-transfer science has established itself as an important independent field, originating from physical chemistry and chemical physics, focussing on paradigms from biology, and gaining momentum from solar-energy research. Here, we review the fundamental concepts of charge transfer, and outline its core role in a broad range of unrelated fields, such as medicine, environmental science, electronics and photonics. The ubiquitous nature of dipoles, for example, sets demands on deepening the understanding of how they affect charge transfer. Charge-transfer electrets, thus, prove important for advancing the field and for interfacing fundamental science with engineering. Synergy between the vastly different aspects of charge-transfer science sets the stage for the broad global impacts that the advances in this field have.
ConspectusGuanine (G) radicals are precursors to DNA oxidative damage, correlated with carcinogenesis and aging. During the past few years, we demonstrated clearly an intriguing effect: G radicals can be generated upon direct absorption of UV radiation with energy significantly lower than the G ionization potential. Using nanosecond transient absorption spectroscopy, we studied the primary species, ejected electrons and guanine radicals, which result from photoionization of various DNA systems in aqueous solution.The DNA propensity to undergo electron detachment at low photon energies greatly depends on its secondary structure. Undetected for monomers or unstacked oligomers, this propensity may be 1 order of magnitude higher for G-quadruplexes than for duplexes. The experimental results suggest nonvertical processes, associated with the relaxation of electronic excited states. Theoretical studies are required to validate the mechanism and determine the factors that come into play. Such a mechanism, which may be operative over a broad excitation wavelength range, explains the occurrence of oxidative damage observed upon UVB and UVA irradiation.Quantification of G radical populations and their time evolution questions some widespread views. It appears that G radicals may be generated with the same probability as pyrimidine dimers, which are considered to be the major lesions induced upon absorption of low-energy UV radiation by DNA. As most radical cations undergo deprotonation, the vast majority of the final reaction products is expected to stem from long-lived deprotonated radicals. Consequently, when G radical cations are involved, the widely used oxidation marker 8-oxodG is not representative of the oxidative damage.Beyond the biological consequences, photogeneration of electron holes in G-quadruplexes may inspire applications in nanoelectronics; although four-stranded structures are currently studied as molecular wires, their behavior as photoconductors has not been explored so far.In the present Account, after highlighting some key experimental issues, we first describe the photoionization process, and then, we focus on radicals. We use as show-cases new results obtained for genomic DNA and OxytrichaG-quadruplexes. Generation and reaction dynamics of G radicals in these systems provide a representative picture of the phenomena reported previously for duplexes and G-quadruplexes, respectively.
Photoinduced electron transfer across an organic capsular wall between excited donors and ground state acceptors is established to occur with rate constants varying in the range 0.2 – 4.0 × 1011 s-1 in aqueous buffer solution. The donor is encapsulated within an anionic supramolecular capsular host and the cationic acceptor remains closer to the donor separated by the organic frame through Coulombic attraction. Such an arrangement results in electron transfer proceeding without diffusion. Free energy of the reaction (G°) and the rate of electron transfer show Marcus relation with inversion. From the plot the and Vel were estimated to be 1.918 eV and 0.0058 eV. Given that the donor remains within the non-polar solvent free confined space, and there is not much change in the environment around the acceptor the observed is believed to be due to ‘internal’ reorganization rather than ‘solvent’ reorganization. A similarity exists between the capsular assembly investigated here and glass and crystals at low temperature where the medium is rigid. The estimated electronic coupling (Vel) implies the existence of interaction between the donor and the acceptor through the capsular wall. Existence of such an interaction is also suggested by 1H NMR spectra. Results of this study suggests that molecules present within a confined space could be activated from outside. This provides an opportunity to probe the reactivity and dynamics of radical ions within an organic capsule.
Single-molecule hybridisation of CY3 dye labelled short oligonucleotides to surface immobilised probes was investigated in zero-mode waveguide nanostructures using a modified DNA sequencer. At longer measuring times, we observed changes of the initial hybridisation fluorescence pulse pattern which we attribute to products created by chemical reactions at the nucleobases. The origin is a charge separated state created by a photo- induced electron transfer from nucleobases to the dye followed by secondary reactions with oxygen and water, respectively. The positive charge can migrate through the hybrid resulting in base modifications at distant sites. Static fluorescence spectra were recorded in order to determine the properties of CY3 stacking to different base pairs, and compared to pulse intensities. A characteristic pulse pattern change was assigned to the oxidation of G to 8-oG besides the formation of a number of secondary products that are not yet identified. Further, we present a method to visualise the degree of chemical reactions to gain an overview of ongoing processes. Our study demonstrates that CY3 is able to oxidise nucleobases in ds DNA, and also in ss overhangs. An important finding is the correlation between nucleobase oxidation potential and fluorescence quenching which explains the intensity changes observed in single molecule measurements. The analysis of fluorescence traces provides the opportunity to track complete and coherent reaction sequences enabling to follow the fate of a single molecule over a long period of time, and to observe chemical reactions in real-time. This opens up the opportunity to analyse reaction pathways, to detect new products and short-lived intermediates, and to investigate rare events due to the large number of single molecules observed in parallel.
The extent of electronic wave function delocalization for the charge carrier (electron or hole) in double helical DNA plays an important role in determining the DNA charge transfer mechanism and kinetics. The size of the charge carrier’s wave func- tion delocalization is regulated by the solvation induced localization and the quantum delocalization among the π stacked base pairs at any instant of time. Using a newly developed localized orbital scaling correction (LOSC) density functional theory method, we accurately characterized the quantum delocalization of the hole wave function in double helical B-DNA. This approach can be used to diagnose the extent of delocalization in fluctuating DNA structures. Our studies indicate that the hole state tends to delocalize among four guanine-cytosine (GC) base pairs and among three adenine- thymine (AT) base pairs when these adjacent bases fluctuate into degeneracy. The relatively small delocalization in AT base pairs is caused by the weaker π − π interaction. This extent of delocalization has significant implications for assessing the role of coherent, incoherent, or flickering coherent carrier transport in DNA.
The main insights on the photoactivated dynamics of Guanine quadruplexes (G4s) recently provided by Quantum Mechanical computations are concisely reviewed here. The experimental steady state absorption and circular dichroism spectra of different topologies can be reproduced and assigned. After light absorption from excited states delocalized over multiple bases, the most important decay pathways involve localization of the excitation over a single base or on two stacked Guanines, excimers with different degree of Charge Transfer character. Two main photochemical reactions are discussed. One involves the photodimerization of two stacked Guanine bases on the ‘neutral’ excimer path. The other, ionization of Guanine, which triggers deprotonation of the resulting cation to form (G-H2)• and (G-H1)• radicals. Both the static and dynamical properties of G4 excited states are ruled by their topology and modulated by the inner coordinated metal ions.
Photoinduced electron transfer can produce radical pairs having two quantum entangled electron spins that can act as spin qubits in quantum information applications. Manipulation of these spin qubits requires selective addressing of each spin using microwave pulses. In this work, photogenerated spin qubit pairs are prepared within chromophore-modified DNA hairpins with varying spin qubit distances, and are probed using transient EPR spectroscopy. By performing pulse-EPR measurements on the shortest hairpin, selective addressing of each spin qubit comprising the pair is demonstrated. Furthermore, these spin qubit pairs have coherence times of more than 4 µs, which provides a comfortable time window for performing complex spin manipulations for quantum information applications. The applicability of these DNA-based photogenerated two-qubit systems is discussed in the context of quantum gate operations, specifically the controlled-NOT gate.
Here we report a synthetic protocol toward a merocyanine (MC) pentamer 1 which represents the first merocyanine oligomer longer than dimer. By continuously decreasing the solvent polarity we demonstrate the stepwise folding from partially folded monomeric and dimeric MC subunits (in chloroform) up to the full pentamer π-stack (in 75% methyl-cyclohexane/25% chloroform) and a subsequent self-assembly of pentamer 1 into larger aggregates (in 80% methylcy-clohexane/20% chloroform). This hierarchical structure formation process became possible due to the predominant dipole-dipole interactions among MC dyes that allowed for a precise modulation of the energy landscape by the solvent polarity. This unprecedented stepwise control of dye assembly via hierarchical dipole-dipole interactions opens a door for a more precise control of dye-dye interactions in artificial multichromophoric ensembles.
We report on the light-switch behavior of two head-to-tail expanded bipyridinium species as a function of their interaction with calf thymus DNA and polynucleotides. In particular, both DNA and polynucleotides containing exclusively adenine or guanine moieties quench the luminescence of the fused expanded bipyridinium species. This behaviour has been rationalized demonstrating that a reductive photoinduced electron transfer process takes place involving both adenine or guanine moieties. The charge separated state so produced recombines in the tens of picoseconds. These results could help on designing new organic substrates for application in DNA probing technology and lab on chip-based sensing systems.
The electron hole injection from a family of spiropyran photoswitches into A/T-duplex DNA has been investigated at molecular level for the first time. Multiscale computations coupled to automatized quantitative wavefunction analysis reveal a pronounced directionality and regioselectivity towards the template strand of the duplex DNA. Our findings suggest that this directional and regioselective photoinduced electron hole transfer could thus be exploited to tailor charge transport processes in DNA in specific applications.
The corpus of electron transfer (ET) theory provides considerable power to describe the kinetics and dynamics of electron flow at the nanoscale. How is it, then, that nucleic acid (NA) ET continues to surprise, while protein-mediated ET is relatively free of mechanistic bombshells? I suggest that this difference originates in the distinct electronic energy landscapes for the two classes of reactions. In proteins, the donor/acceptor-to-bridge energy gap is typically several-fold larger than in NAs. NA ET can access tunneling, hopping, and resonant transport among the bases, and fluctuations can enable switching among mechanisms; protein ET is restricted to tunneling among redox active cofactors and, under strongly oxidizing conditions, a few privileged amino acid side chains. This review aims to provide conceptual unity to DNA and protein ET reaction mechanisms. The establishment of a unified mechanistic framework enabled the successful design of NA experiments that switch electronic coherence effects on and off for ET processes on a length scale of multiple nanometers and promises to provide inroads to directing and detecting charge flow in soft-wet matter. Expected final online publication date for the Annual Review of Physical Chemistry Volume 70 is April 20, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Achieving high-yielding photoinduced charge separation through the π-stacked bases of DNA is a critical requirement for realizing numerous DNA-based technologies. In the current work, we combine two strategies for achieving high-yield charge separation. First, a chromophore with a high driving force for charge injection, naphthalenediimide (NDI), is used since it generates hot carriers that enhance charge transfer rates. Second, a diblock DNA sequence is used with two or three adenines followed by a series of guanines to implement an energy landscape that accelerates charge separation while retarding charge recombination. The photoinduced dynamics of these NDI diblock oligomers with and without a terminal hole acceptor are probed by femtosecond transient absorption spectroscopy. The measured rate constants for various charge separation and recombination processes are interpreted within the context of a full kinetic model of these systems. We find that the A2 and A3 oligomers achieve similar charge separation yields for a given length, yet the critical recombination process that determines these yields occurs at different distances from the NDI chromophore and on different time scales. This type of analysis could be used to predict charge separation efficiencies in candidate DNA structures.
The ability to prepare physical qubits in specific initial quantum states is a critical requirement for their use in quantum information science (QIS). Sub-nanosecond photoinduced electron transfer in a structurally well-defined donor-acceptor system can be used to produce an entangled spin qubit (radical) pair in a pure initial singlet state fulfilling this criterion. Synthetic DNA is a promising platform on which to build spin qubit arrays with fixed spatial relationships; therefore, we have prepared a series of DNA hairpins in which naphthalenediimide (NDI) is the chromophore/acceptor hairpin linker, variable length diblock A- and G-tracts are intermediate donors, and a stilbenediether (Sd) is the terminal donor. Photoexcitation of NDI in these DNA hairpins generates high yield, long-lived, entangled spin qubit pairs at 85 K, and time-resolved and pulse electron paramagnetic resonance (EPR) spectroscopies are used to probe their spin dynamics. Specifically, measurements of the distance-dependent dipolar coupling between the two spins is used to obtain the average spin qubit pair distance and reveals that one of the spins is fully delocalized across up to five adjacent guanines in a G-tract on the EPR timescale. We have recently shown that extensive spin hopping between degenerate sites accessible to one spin of the pair may result in spin decoherence. However, we observe a strong out-of-phase electron spin echo envelope modulation (OOP-ESEEM) signal from the NDI•- - Sd•+ spin qubit pair in DNA hairpins showing that spin coherence is maintained across a two adenine A-tract followed by a 2-4 guanine G-tract as a result of rapid spin transport to Sd. These results demonstrate that pulse-EPR can manipulate coherent spin states in DNA hairpins, which is essential for quantum gate operations relevant to QIS applications.
In the past few decades, charge transfer in DNA has attracted considerable attention from researchers in a wide variety of fields, including bioscience, physical chemistry, and nanotechnology. Charge transfer in DNA has been investigated using various techniques. Among them, time-resolved spectroscopic methods have yielded valuable information on charge transfer dynamics in DNA, providing an important basis for numerical practical applications such as development of new therapy applications and nanomaterials. In DNA, holes and excess electrons act as positive and negative charge carriers, respectively. Although hole transfer dynamics have been investigated in detail, the dynamics of excess electron transfer have only become clearer relatively recently. In the present paper, we summarize studies on the dynamics of hole and excess electron transfer conducted by several groups including our own.
DNA-based molecular electronics will require charges to be transported from one site within a 2D or 3D architecture to another. While this has been shown previously in linear, π-stacked DNA sequences, the dynamics and efficiency of charge transport across a DNA three-way junction (3WJ) have yet to be determined. Here, we present an investigation of hole transport and trapping across a DNA-based three-way junction systems by a combination of femtosecond transient absorption spectroscopy and molecular dynamics simulations. Hole transport across the junction is proposed to be gated by conformational fluctuations in the ground state which bring the transiently-populated hole carrier nucleobases into better aligned geometries on the nanosecond timescale, thus modulating the - electronic coupling along the base pair sequence.
Rapid photoinduced electron transfer is demonstrated over a distance of greater than 40 angstroms between metallointercalators that are tethered to the 5' termini of a 15-base pair DNA duplex. An oligomeric assembly was synthesized in which the donor is Ru(phen)2dppz2+ (phen, phenanthroline, and dppz, dipyridophenazine) and the acceptor is Rh(phi)2phen3+ (phi, phenanthrenequinone diimine). These metal complexes are intercalated either one or two base steps in from the helix termini. Although the ruthenium-modified oligonucleotide hybridized to an unmodified complement luminesces intensely, the ruthenium-modified oligomer hybridized to the rhodium-modified oligomer shows no detectable luminescence. Time-resolved studies point to a lower limit of 10(9) per second for the quenching rate. No quenching was observed upon metallation of two complementary octamers by Ru(phen)3(2+) and Rh(phen)3(3+) under conditions where the phen complexes do not intercalate. The stacked aromatic heterocycles of the DNA duplex therefore serve as an efficient medium for coupling electron donors and acceptors over very long distances.
The distance dependence of photoinduced electron transfer in duplex DNA was determined for a family of synthetic DNA hairpins
in which a stilbene dicarboxamide forms a bridge connecting two oligonucleotide arms. Investigation of the fluorescence and
transient absorption spectra of these hairpins established that no photoinduced electron transfer occurs for a hairpin that
has six deoxyadenosine-deoxythymidine base pairs. However, the introduction of a single deoxyguanosine-deoxycytidine base
pair resulted in distance-dependent fluorescence quenching and the formation of the stilbene anion radical. Kinetic analysis
suggests that duplex DNA is somewhat more effective than proteins as a medium for electron transfer but that it does not function
as a molecular wire.
Electron transfer (ET) processes in DNA are of current interest because of their involvement in oxidative strand cleavage reactions and their relevance to the development of molecular electronics. Two mechanisms have been identified for ET in DNA, a single-step tunneling process and a multistep charge-hopping process. The dynamics of tunneling reactions depend on both the distance between the electron donor and acceptor and the nature of the molecular bridge separating the donor and acceptor. In the case of protein and alkane bridges, the distance dependence is not strongly dependent on the properties of the donor and acceptor. In contrast, we show here that the distance decay of DNA ET rates varies markedly with the energetics of the donor and acceptor relative to the bridge. Specifically, we find that an increase in the energy of the bridge states by 0.25 eV (1 eV = 1.602 x 10(-19) J) relative to the donor and acceptor energies for photochemical oxidation of nucleotides, without changing the reaction free energy, results in an increase in the characteristic exponential distance decay constant for the ET rates from 0.71 to 1.1 A(-1). These results show that, in the small tunneling energy gap regime of DNA ET, the distance dependence is not universal; it varies strongly with the tunneling energy gap. These DNA ET reactions fill a "missing link" or transition regime between the large barrier (rapidly decaying) tunneling regime and the (slowly decaying) hopping regime in the general theory of bridge-mediated ET processes.
The crystal structure of the DNA dodecamer duplex CATGGGCCCATG lies on a structural continuum along the transition between
A‐ and B‐DNA. The dodecamer possesses the normal vector plot and inclination values typical of B‐DNA, but has the crystal
packing, helical twist, groove width, sugar pucker, slide and x‐displacement values typical of A‐DNA. The structure shows highly ordered water structures, such as a double spine of water
molecules against each side of the major groove, stabilizing the GC base pairs in an A‐like conformation. The different hydration
of GC and AT base pairs provides a physical basis for solvent‐dependent facilitation of the A↔B helix transition by GC base
pairs. Crystal structures of CATGGGCCCATG and other A/B‐DNA intermediates support a ‘slide first, roll later’ mechanism for
the B→A helix transition. In the distribution of helical parameters in protein–DNA crystal structures, GpG base steps show
A‐like properties, reflecting their innate predisposition for the A conformation.
The crystal structure of [d(CGCAAATTTGCG)]2 has been determined to 1.5 A resolution, representing the first high-resolution structure of this DNA fragment. The ion interactions are novel. A spermine molecule replaces a Mg2+ observed in analogous structures. Unlike lower-resolution structures, the minor groove is narrow and the major groove lacks extra Watson-Crick hydrogen bonds. In addition, a monolayer of solvent sites, including a "spine of hydration", is visible in the minor groove. The crystal of [d(CGCAAATTTGCG)]2 was grown from a solution containing spermine, magnesium, and lithium. The conformation recapitulates that of "monovalent-minus" DNA.
The hole transport dynamics of DNA hairpins possessing a stilbene electron acceptor and donor along with a modified guanine (G) nucleobase, specifically 8-(4′-phenylethynyl)deoxyguanosine, or EG, have been investigated. The nearly indistinguishable oxidation potentials of EG and G and unique spectroscopic characteristics of EG+• make it well-suited for directly observing transient hole occupation during charge transport between a stilbene electron donor and acceptor. In contrast to the cation radical G+•, EG+• possesses a strong absorption near 460 nm and has a distinct Raman-active ethynyl stretch. Both spectroscopic characteristics are easily distinguished from those of the stilbene donor/acceptor radical ion chromophores. Employing EG, we observe its role as a shallow hole trap, or as an intermediate hole transport site when a deeper trap state is present. Using a combination of ultrafast absorption and stimulated Raman spectroscopies, the hole-transport dynamics are observed to be similar in systems having EG vs. G bases, with small perturbations to the charge transport rates and yields. These results show EG can be deployed at specified locations throughout the sequence to report on hole occupancy, thereby enabling detailed monitoring of the hole transport dynamics with base-site specificity.
The dynamics of electron injection have been investigated in intramolecular i-motif conjugates possessing stilbenediether (Sd) and perylenediimide (PDI) chromophores separated by either four or six hemi-protonated cytosine C-C base pairs assembled with synthetic loops. Circular dichroism spectra are consistent with the formation of i-motif structures in the absence or presence of Sd and PDI chromophores. The fluorescence of the Sd chromophore is essentially completely quenched by neighboring C-C base pairs, consistent with their function as an electron donor and electron acceptor, respectively. However, the fluorescence of the PDI chromophore is only partially quenched. The dynamics of electron injection from singlet Sd into the i-motif and subsequent charge recombination has been determined by femtosecond transient absorption (fsTA) spectroscopy and compared with the results for electron injection and charge recombination in Sd-linked hairpins possessing cytosine-guanine (C-G) or 5-fluorourancil-adenine (F-A) base pairs. While charge injection is ultrafast (< 0.8 ps) for the i-motifs, charge transport across the i-motif C-C base pairs to the PDI electron trap is not observed. The absence of electron transport is related to the structure of the stacked C-C base pairs in the i motif.
Steady state spectroscopy, femtosecond transient absorption spectroscopy (fsTA), and femtosecond stimulated Raman spectroscopy (FSRS) of DNA mini-hairpins possessing a diphenylacetylenedicarboxamide (DPA) linker and 1-3 adenine-thymine (A-T) or guanine-cytosine (G-C) base pairs have been investigated. Ultraviolet and circular dichroism (UV and CD) spectra are consistent with ground state conformations that are predominantly base-paired and -stacked for conjugates possessing two or three base pairs; however, they offer no information concerning the conformation of conjugates possessing a single base pair. fsTA spectra are indicative of -stacked structures excepted in the case of the conjugate possessing a single G-C base pair. All of the conjugates display transient absorption bands characteristic of the DPA-. anion radical. Conjugates possessing two or three G-C base pairs display a transient absorption band characteristic of the short-lived G+. cation radical. The mini-hairpins with 1-3 A-T base pairs do not display the transient absorption band characteristic of the (An+.) polaron. This implies that an A-tract with three base pairs is too short to support polaron formation.
The dynamics and efficiency of photoinduced charge transport has been investigated in DNA capped hairpins possessing a stilbenedicarboxamide (Sa) hole donor and stilbenediether (Sd) hole acceptor separated by DNA G-quadruplex structures possessing 2-to-4 tetrads by means of femtosecond and nanosecond transient absorption spectroscopy with global analysis. The results for the quadruplex structures are compared with those for the corresponding duplex structures having G-C base pairs in place of the G-tetrads. Following photoinduced charge separation to form a contact radical ion pair, hole transport to form the Sa ./Sd+. charge-separated state is slower but more efficient for the quadruplex vs. duplex structures. Thus the G-quadruplex serves as an effective conduit for positive charge rather than as a hole trap when inserted into a duplex, as previously postulated.
Charge transport through the DNA double helix is of fundamental interest in chemistry and biochemistry, but also has potential technological applications such as for DNA-based nanoelectronics. For the latter, it is of considerable interest to explore ways to influence or enhance charge transfer. In this Article we demonstrate a new mechanism for DNA charge transport, namely 'deep-hole transfer', which involves long-range migration of a hole through low-lying electronic states of the nucleobases. Here, we demonstrate, in a combined experimental and theoretical study, that it is possible to achieve such transfer behaviour by changing the energetics of charge injection. This mechanism leads to an enhancement in transfer rates by up to two orders of magnitude and much weaker distance dependence. This transfer is faster than relaxation to the lowest-energy state, setting this mechanism apart from those previously described. This opens up a new direction to optimize charge transfer in DNA with unprecedented charge-transfer rates. © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
The excited state behavior of DNA hairpins possessing a diphenylacetylenedicarboxamide (DPA) linker separated from a single guanine‒cytosine (G‒C) base pair by zero-to-six adenine‒thymine (A‒T) base pairs has been investigated by a combination of femtosecond and nanosecond transient absorption spectroscopy and femtosecond stimulated Raman spectroscopy. In the case of hairpins with zero or one A‒T base pair separating DPA and G, formation of both DPA anion radical (DPA-•) and G cation radical (G+•) are directly observed and characterized by their transient absorption and stimulated Raman spectra. For hairpins with two or more intervening A‒T base pairs, the transient absorption spectra of DPA-• and the adenine polaron (An+•) are observed. In addition to characterization of the hole carriers, the dynamics of each step in the charge separation and charge recombination process as well as the overall efficiency of charge separation have been determined, thus providing a complete account of the mechanism and dynamics of photoinduced charge transport in these DNA hairpins.
The oxidation of guanine (G) is studied by using the transient absorption and time-resolved resonance Raman (TR<sup>3</sup>) spectroscopies combined with pulse radiolysis. The transient absorption spectral change demonstrates that the neutral radical of G (G<sup)•</sup>(-H<sup>+</sup>)), generated by the deprotonation of G radical cation (G<sup>•+</sup>), is rapidly converted to other G radical species. The formation of this species shows the pH-dependence, suggesting that it is the G radical cation (G<sup>•+</sup>)' formed from the protonation at the N7 of G<sup)•</sup>(-H<sup>+</sup>). On one hand, most of Raman bands of (G<sup>•+</sup>)' are up-shifted relative to those of G, indicating the increase in the bonding order of pyrimidine (Pyr) and imidazole rings. The (G<sup>•+</sup>)' exhibits the characteristic CO stretching mode at 1266 cm-1 corresponding to a C-O single bond, indicating that the unpaired electron in (G•+) is localized on the oxygen of Pyr ring.
Intermolecular static and dynamic fluorescence quenching constants of eight coumarin derivatives by nucleobase derivatives have been determined in aqueous media. One common sequence of the quenching efficiency has been found for the nucleobases. The feasibility of a photoinduced electron transfer reaction for the nucleobase-specific quenching of fluorescent dyes is investigated by the calculation of the standard free energy changes with the Rehm-Weller equation. A complete set of one-electron redox potential data for the nucleobases are determined electrochemically in aprotic solvents for the first time, which are compared with values obtained by various other methods. Depending on the redox properties of the fluorescent dyes, the sequences of the quenching efficiencies can be rationalized by the orders of electrochemical oxidation potentials (vs NHE) of nucleosides (dG (+1.47 V) < dA ( dC approximate to dT < U (greater than or equal to +2.39 V)) and reduction potentials (de (( -2.76 V) < dA < dC approximate to dT < U (-2.07 V)). The correlation between the intermolecular dynamic quenching constants and the standard free energy of photoinduced electron transfer according to the classical Marcus equation indicates that photoinduced electron transfer is the rate-limiting step. However, an additional, water-specific gain of free energy between -0.5 and -0.9 eV shows that additional effects, like a coupled proton transfer and a hydrophobic effect, have to be considered, too. Furthermore, the capability of the nucleobases to form ground state complexes with fluorescent dyes is influenced by their redox potentials. The relevance of these observations to current efforts for DNA sequencing with a detection by laser-induced fluorescence and their application to other dyes are discussed.
The effects of an artificial cyclohexyl base pair on the quantum yields of fluorescence and dynamics of charge separation and charge recombination have been investigated for several synthetic DNA hairpins. The hairpins possess stilbenedicarboxamide, perylenediimide, or naphthalenediimide linkers and base-paired stems. In the absence of the artificial base pair hole injection into both adenine and guanine purine bases is exergonic and irreversible, except in the case of stilbene with adenine for which it is slightly endergonic and reversible. Insertion of the artificial base pair renders hole injection endergonic or isoergonic except in the case of the powerful naphthalene acceptor for which it remains exergonic. Both hole injection and charge recombination are slower for the naphthalene acceptor in the presence of the artificial base pair than in its absence. The effect of an artificial base pair on charge separation and charge recombination in hairpins possessing stilbene and naphthalene acceptor linkers and a stilbenediether donor capping group has also been investigated. In the case of the stilbene acceptor-stilbene donor capped hairpins photoinduced charge separation across six base pairs is efficient in the absence of the artificial base pair but does not occur in its presence. In the case of the naphthalene acceptor-stilbene donor capped hairpins the artificial base pair slows but does not stop charge separation and charge recombination, leading to the formation of long-lived charge separated states.
We have prepared a G-quadruplex (GQ-1) that incorporates an 8-(4'-aminophenylethynyl)guanine (GEAn) electron donor covalently attached to a 4-aminonaphthalene-1,8-imide (ANI) chromophore and a naphthalene-1,8:4,5-bis(dicarboximide) (NDI) electron acceptor (GEAn-ANI-NDI, 1). In the presence of KPF6 in tetrahydrofuran (THF), 1 self-assembles into a monodisperse, C4-symmetric GQ-1 with small spatial intra-quadruplex overlap between the ANI-NDI units. Photoexcitation of monomeric 1 induces the two-step charge transfer GEAn-1*ANI-NDI → GEAn+•-ANI-•-NDI → GEAn+•-ANI-NDI-• that occurs in τCS1 = 5 ps and τCS2 = 330 ps, respectively, while charge recombination in ca. 300 ns. Sharpening of the GEAn+• transient absorption and a shift of the ethynyl vibrational frequency in 1 were observed, concomitant with the stepwise electron transfer from ANI-• to NDI. Formation of GQ-1 from 1 in THF increases the secondary charge-shifting rate (τCS2 = 110 ps), and results in no change in ethynyl vibrational frequency. Charge recombination in GQ-1 is slowed by enhanced radical-pair intersystem crossing driven by the greater number of hyperfine couplings in the assembly. Moreover, time-resolved EPR spectroscopy shows that the spin-spin-exchange interaction (J) between the radicals of GEAn+•-ANI-NDI-• within GQ-1 is smaller than that of 1, suggesting that the spin (charge) density in GEAn+• is more dispersed in GQ-1. The spectroscopic results are consistent with hole sharing among the guanines within the G-quadruplex that is kinetically competitive with the formation of GEAn+•. This suggests that G-quadruplexes can serve as effective hole conduits in ordered donor-acceptor assemblies.
The mechanism and dynamics of photoinduced electron injection and charge recombination have been investigated for several series of DNA hairpins. The hairpins possess a stilbenediether linker which serves as an electron donor and base pair stems which possess different pyrimidine bases adjacent to the linker. Hairpins with adjacent thymine-adenine (T-A) base pairs undergo fast electron injection and relatively slow charge recombination with rate constants that are not strongly dependent upon the following base pair. Hairpins with adjacent cytosine-guanine (C-G) base pairs undergo reversible electron injection and much faster charge recombination than those with adjacent T-A base pairs. Hairpins with 5-fluorouracil or other halogenated pyrimidines in their first and second base pair undergo fast electron injection and multiexponential charge recombination. The difference in kinetic behavior for the different series of hairpins and its implications for the formation of long-lived charge-separated states are discussed and compared to results reported previously for other electron donor chromophores.
The solvent dependent free enthalpies of exciplex and radical ion pair formation in solution have been calculated on the basis of the experimentally obtained thermodynamic and spectroscopic values and with the aid of theoretical considerations concerning solvent polarity effects in general.
Significance
Electron transport through DNA plays a central role in nucleic acid damage and repair, and it is usually modeled using a carrier tunneling mechanism (at short distances) and a hopping mechanism (at longer distances). We find that fluctuations into transient geometries that bring multiple bases into electronic degeneracy may support band-like transport during the resonance lifetimes over a distance of ≲15 Å, obviating the need to invoke electron tunneling at short distances. This line of research may help to reveal mechanisms of charge transport in multiheme proteins, bacterial nanowires, and synthetic nanowires, and may also assist in framing the mechanisms of coherent multipigment excitonic transport in light-harvesting proteins.
Base stacking in DNA is related to long-living excited states whose molecular nature is still under debate. To elucidate the molecular background we study well-defined oligonucleotides with natural bases, which allow selective UV excitation of one single base in the strand. IR probing in the picosecond regime enables us to dissect the contribution of different single bases to the excited state. All investigated oligonucleotides show long-living states on the 100-ps time scale, which are not observable in a mixture of single bases. The fraction of these states is well correlated with the stacking probabilities and reaches values up to 0.4. The long-living states show characteristic absorbance bands that can be assigned to charge-transfer states by comparing them to marker bands of radical cation and anion spectra. The charge separation is directed by the redox potential of the involved bases and thus controlled by the sequence. The spatial dimension of this charge separation was investigated in longer oligonucleotides, where bridging sequences separate the excited base from a sensor base with a characteristic marker band. After excitation we observe a bleach of all involved bases. The contribution of the sensor base is observable even if the bridge is composed of several bases. This result can be explained by a charge delocalization along a well-stacked domain in the strand. The presence of charged radicals in DNA strands after light absorption may cause reactions-oxidative or reductive damage-currently not considered in DNA photochemistry.
We developed a model for hole migration along relatively short DNA hairpins with fewer that seven adenine (A):thymine (T) base pairs. The model was used to simulate hole migration along poly(A)-poly(T) sequences with a particular emphasis on the impact of partial hole localization on the different rate processes. The simulations, performed within the framework of the stochastic surrogate Hamiltonian approach, give values for the arrival rate in good agreement with experimental data. Theoretical results obtained for hairpins with fewer than three A:T base pairs suggest that hole transfer along short hairpins occurs via superexchange. This mechanism is characterized by the exponential distance dependence of the arrival rate on the donor/acceptor distance, ka ≃ e-βR, with β = 0.9 Å-1. For longer systems, up to six A:T pairs, the distance dependence follows a power law ka ≃ R-η with η = 2. Despite this seemingly clear signature of unbiased hopping, our simulations show the complete delocalization of the hole density along the entire hairpin. According to our analysis, the hole transfer along relatively long sequences may proceed through a mechanism which is distinct from both coherent single-step superexchange and incoherent multistep hopping. The criterion for the validity of this mechanism intermediate between superexchange and hopping is proposed. The impact of partial localization on the rate of hole transfer between neighboring A bases was also investigated.
The structure and properties of the electron donor-acceptor complexes formed between methyl viologen (MV) and purine nucleosides and nucleotides in water and the solid state have been investigated using a combination of experimental and theoretical methods. Solution studies were performed using UV-vis and 1H NMR spectroscopy. Theoretical calculations were performed within the framework of density functional theory (DFT). Energy decomposition analysis indicates that dispersion and induction (charge-transfer) interactions dominate the total binding energy, whereas electrostatic interactions are largely repulsive. The appearance of charge transfer bands in the absorption spectra of the complexes are well described by time-dependent (TD) DFT and are further explained in terms of the redox properties of purine monomers and solvation effects. Crystal structures are reported for complexes of methyl viologen with the purines 2'-deoxyguanosine 3'-monophosphate GMP (DAD'DAD' type) and 7-deazaguanosine zG (DAD'ADAD' type). Comparison of the structures determined in the solid state and by theoretical methods in solution provides valuable insights into the nature of charge-transfer interactions involving purine bases as electron donors.
The -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 -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.
The synthesis and properties of a perylenediamide diol linker and several DNA hairpins possessing this linker are described. The diol linker absorbs and fluoresces strongly in the visible. Hairpins having poly(dA)–poly(dT) stems have fluorescence quantum yields and decay times similar to those of the linker, indicating that hole injection does not occur from the singlet excited linker into the base pair domain. Fluorescence quenching by dG or dZ bases is observed when these bases are located near the linker. The strong distance dependence of fluorescence quenching is consistent with a superexchange mechanism for electron transfer. Failure to observe formation of the linker anion radical by means of femtosecond time resolved absorption spectroscopy is attributed to fast charge recombination. The properties and behavior of the perylene linker and its hairpins are compared to those of other arenedicarboxamide linkers.Graphical abstractDNA hairpins possessing perylenedicarboxamide linkers are strongly fluorescent except when a guanine or deazaguanine base is located adjacent to the linker.
Bis(oligonucleotide) conjugates with synthetic linkers connecting short complementary oligonucleotides are known to form synthetic DNA or RNA hairpins which are, in some cases, more stable than natural hairpins which possess oligonucleotide linkers. The authors report here that conjugates possessing stilbenediether (SE) linkers form exceptionally stable (poly)dT-SE-(poly)dA hairpins. The crystal structure of a Se-bridged hairpin confirms that it adopts a B-form structure in which the stilbene is -stacked with the adjacent base pair. The stilbenediether also mediates novel lattice interactions that are distinct from those normally found in DNA crystals. The singlet excited state of the stilbenediether is a strong electron donor which is rapidly quenched by either neighboring dT-dA or dC-dG base pairs which function as electron acceptors. This behavior is complementary to that of conjugates possessing a stilbenedicarboxamide linker (SA, Chart 1), which serves as an electron acceptor.
A linker containing a terephthalamide group, -P(O)(O-)O(CH2)6NHC(O)C6H4C(O)NH(CH2)6OP(O)(O-)-, is shown to be an effective structural element for organizing oligonucleotide chains in solution. Capping a pair of complementary oligonucleotides with this linker leads to marked enhancement in stability of the Watson-Crick duplex structure. Joining a pair of thymidylate oligomers with this linker gives a compound exhibiting unusually high affinity for oligo(dA) strands; even a tetramer unit can be recognized in dilute solution. Presumably Hoogsteen as well as Watson-Crick hydrogen bonding stabilizes a bimolecular 'triplex". Both types of linkage (i.e., joining two complementary strands and joining two pyrimidine strands) are embodied in the novel compound, d(TTTTTT-X-TTTTTT-X-AAAAAA), and function jointly in stabilizing a doubly folded monomolecular triple stranded structure (T(m) 58-degrees-C, 1 M NaCl; -X- represents the terephthalamide linker group).
Time-resolved resonance Raman spectra of the lowest excited triplet state, T{sub 1}, the radical cation, R{sup {sm_bullet}+}, and the radical anion, R{sup {sm_bullet}{minus}}, of diphenylacetylene (DPA) have been measured. Vibrational assignments of the Raman bands of these transients have been based on the frequency shifts on phenyl deuterations and {sup 13}C substitution of the C{triple_bond}C triple bond. The Raman spectra have shown that the C{triple_bond}C stretch exhibits large low-frequency shifts in the order, S{sub 0} (2217 cm{sup {minus}1}), R{sup {sm_bullet}+} (2142 cm{sup {minus}1}), R{sup {sm_bullet}{minus}} (2091 cm{sup {minus}1}), and T{sub 1} (1972 cm{sup {minus}1}), indicating that the C{triple_bond}C triple bond weakens dramatically in this sequence. The same trend, though not large, has been observed for phenyl skeletal vibrations as well. The dependence of the yield of R{sup {sm_bullet}+} on the pump laser power has revealed that the photoionization of DPA to produce R{sup {sm_bullet}+} is a biphotonic ionization can occur through the T{sub 1} state. 21 refs., 10 figs., 1 tab.
We report here the effect of replacing one or both of the purine or pyrimidine blocks of a diblock stilbene donor-acceptor capped hairpin with locked nucleic acid (LNA) bases on the dynamics and efficiency of hole transport. The structures of the DNA and LNA:DNA hybrids are tentatively assigned to B- or A-type structures on the basis of their circular dichroism spectra. Replacing the bases in either the A-block or the G-block of the diblock DNA hairpin with LNA bases results in a modest decrease in the base-to-base hopping rate constant and quantum yield for charge separation. Somewhat larger decreases are observed when all of the purine or pyrimidine bases are replaced by LNA bases.
The dynamics of photoinduced charge separation and charge recombination in synthetic DNA hairpins have been investigated by means of femtosecond and nanosecond transient spectroscopy. The hairpins consist of a stilbene linker connecting two complementary 6-mer or 7-mer oligonucleotide strands. Base pairing between these strands results in formation of hairpins in which the stilbene is approximately parallel to the adjacent base pair. The singlet stilbene is selectively quenched by guanine, but not by the other nucleobases, via an electron-transfer mechanism in which the stilbene singlet state is the electron acceptor and guanine is the electron donor. In a hairpin containing only A:T base pairs, no quenching occurs and the restricted geometry results in a long stilbene lifetime and high fluorescence quantum yield. In families of hairpins which contain a single G:C base pair at varying locations in the hairpin stem, the stilbene fluorescence lifetime and quantum yield decrease as the stilbene-guanine distance decreases. Transient absorption spectroscopy is used to monitor the disappearance of the stilbene singlet and the formation and decay of the stilbene anion radical. Analysis of these data provides the rate constants for charge separation and charge recombination. Both processes show an exponential decrease in rate constant with increasing stilbene-guanine distance. Thus, electron transfer is concluded to occur via a single-step superexchange mechanism with a distance dependence) 0.7 Å -1 for charge separation and 0.9 Å -1 for charge recombination. The rate constants for charge separation and charge recombination via polyA vs polyT strands are remarkably similar, slightly larger values being observed for polyA strands. The dynamics of electron transfer in hairpins containing two adjacent G:C base pairs have also been investigated. When the guanines are in different strands, the second guanine has little effect on the efficiency or dynamics of electron transfer. However, when the guanines are in the same strand, somewhat faster charge separation and slower charge recombination are observed than in the case of hairpins with a single G:C base pair. Thus, the GG step functions as a shallow hole trap. The relationship of these results to other theoretical and experimental studies of electron transfer in DNA is discussed.
Photoinduced electron transfer (PET) in DNA can occur via one of two mechanisms, single-step superexchange and multi-step hole hopping. The dynamics of superexchange charge separation and charge recombination has recently been investigated in several structurally well-defined systems. In each of these systems, an electron acceptor is separated from a guanine or deazaguanine nucleobase donor by a variable number of A:T base pairs. The results of experimental studies on these and related systems are presented and analyzed within the framework of semi-classical electron transfer theory. Comparison of the results with those for other bridge-mediated electron transfer systems indicates that the π-stacked bases of DNA provide a better medium for electron transfer than the sigma bonded pathways of proteins and saturated hydrocarbons but do not function as a molecular wire.
Transport of positive charge or holes in DNA occurs via a thermally activated multi-step hopping mechanism. The fastest hopping rates reported to date are those for repeating poly(purine) sequences in which hopping occurs via a random walk mechanism with rate constants of k(hop) = 4.3 × 10(9) s(-1) for poly(dG) and 1.2 × 10(9) s(-1) for poly(dA). We report here the dynamics of charge separation in DNA conjugates possessing repeating 7-deazaadenine (dzA) sequences. These data provide an estimated value of k(hop) = 4.2 × 10(10) s(-1) for poly(dzA), an order of magnitude faster than for poly(dG).
We report the measurement of distance- and temperature-dependent rate constants for charge separation in capped hairpins in which a stilbene hole acceptor and hole donor are separated by A(3)G(n) diblock polypurine sequences consisting of 3 adenines and 1-19 guanines. The longer diblock systems obey the simplest model for an unbiased random walk, providing a direct measurement of k(hop) = 4.3 × 10(9) s(-1) for a single reversible G-to-G hole hopping step, somewhat faster than the value of 1.2 × 10(9) s(-1) calculated for A-tract hole hopping. The temperature dependence for hopping in A(3)G(13) provides values of E(act) = 2.8 kcal/mol and A = 7 × 10(9) s(-1), consistent with a weakly activated, conformationally gated process.
A kinetics model is designed to investigate the charge separation (CT) process in stilbene-capped DNA hairpins composed of AT base pairs. This model combines standard tunneling and hopping electron transport with exciplex formation upon photoexcitation of the acceptor stilbene and its neighboring adenine and is capable of interpreting the CT rate and yield data within experimental accuracy. An analysis of hopping transport within the framework of a 1-D diffusion model results in a calculation of the nearest-neighbor CT rate to be approximately 1.2 ns(-1). In agreement with previous experimental and theoretical work, it is ascertained through a novel application of an extension to classical Marcus theory that the nearest-neighbor CT is adiabatic with reorganization energy lambda approximately 0.83 eV. The kinetics model can be extended to accurately characterize CT in other poly(A)-poly(T) systems with different hole donors (naphthaldiimide and 2-aminopurine) and acceptors (phenothiazine and guanine).
Some of the critical characteristics of DNA charge transport (CT) chemistry were studied. Among the most interesting characteristics of charge transport in DNA is the long distance over which it occurs. It is notable that initial measurements of DNA-mediated charge transport for both photooxidation experiments and device experiments found rates and conductivities spanning several orders of magnitude over comparable distances, depending on the experimental conditions. The structure of DNA is central to its extraordinary effectiveness as the genetic template for the cell. The ionic strength can dictate the conformation of DNA. A high ionic strength drives the transition from the B-form to the more extended Z-form of DNA. Poor base stacking, associated with this condensed structure, leads to less efficient DNA-mediated CT. In addition to global changes in structural integrity, subtle modulations to structure can also have profound effects on the rates and yields of DNA-mediated CT. It is clear that DNA, when adequately coupled between the donor and acceptor, can competently mediate CT over long distances.
DNA charge transfer chemistry has been subject of considerable interest with consequences in the formation of oxidative damage to the DNA which can result in mutagenesis or carcinogenesis. In this article, important examples of spectro-scopical and biochemical assays are compared and discussed in terms of the effiencies, rates, and mechanisms. Coupled with the demonstration that such charge transfer can be modulated both negatively and positively by DNA-binding proteins, these observations therefore suggest the intriguing possibility that DNA-mediated charge transfer chemistry is biological relevant and may play a role in cellular processes. Additionally, charge transfer chemistry plays a growing role in the recent development of DNA chips detecting mutations or lesions of nucleic acids.
The realization of highly efficient photoinduced charge separation across the pi-stacked base pairs in duplex DNA remains elusive. The low efficiencies (<5%) typically observed for charge separation over a dozen or more base pairs are a consequence of slow charge transport and rapid charge recombination. We report here a significant (5-fold or greater) enhancement in the efficiency of charge separation in diblock purine oligomers consisting of two or three adenines followed by several guanines, when compared to oligomers consisting of a single purine or alternating base sequences. This approach to wire-like behavior is attributed to both slower charge recombination and faster charge transport once the charge reaches the G-block in these diblock systems.
A perylenediimide chromophore (P) was incorporated into DNA hairpins as a base-pair surrogate to prevent the self-aggregation of P that is typical when it is used as the hairpin linker. The photoinduced charge-transfer and spin dynamics of these hairpins were studied using femtosecond transient absorption spectroscopy and time-resolved EPR spectroscopy (TREPR). P is a photooxidant that is sufficiently powerful to quantitatively inject holes into adjacent adenine (A) and guanine (G) nucleobases. The charge-transfer dynamics observed following hole injection from P into the A-tract of the DNA hairpins is consistent with formation of a polaron involving an estimated 3-4 A bases. Trapping of the (A 3-4) (+*) polaron by a G base at the opposite end of the A-tract from P is competitive with charge recombination of the polaron and P (-*) only at short P-G distances. In a hairpin having 3 A-T base pairs between P and G ( 4G), the radical ion pair that results from trapping of the hole by G is spin-correlated and displays TREPR spectra at 295 and 85 K that are consistent with its formation from (1*)P by the radical-pair intersystem crossing mechanism. Charge recombination is spin-selective and produces (3*)P, which at 85 K exhibits a spin-polarized TREPR spectrum that is diagnostic of its origin from the spin-correlated radical ion pair. Interestingly, in a hairpin having no G bases ( 0G), TREPR spectra at 85 K revealed a spin-correlated radical pair with a dipolar interaction identical to that of 4G, implying that the A-base in the fourth A-T base pair away from the P chromophore serves as a hole trap. Our data suggest that hole injection and transport in these hairpins is completely dominated by polaron generation and movement to a trap site rather than by superexchange. On the other hand, the barrier for charge injection from G (+*) back onto the A-T base pairs is strongly activated, so charge recombination from G (or even A trap sites at 85 K) most likely proceeds by a superexchange mechanism.
The deprotonation of guanine cation radical (G+*) in oligonucleotides (ODNs) was measured spectroscopically by nanosecond pulse radiolysis. The G+* in ODN, produced by oxidation with SO4-*, deprotonates to form the neutral G radical (G(-H)*). In experiments using 5-substituted cytosine-modified ODN, substitution of the cytosine C5 hydrogen by a methyl group increased the rate constant of deprotonation, whereas replacement by bromine decreased the rate constant. Kinetic solvent isotope effects on the kinetics of deoxyguanosine (dG) and ODN duplexes were examined in H2O and D2O. The rate constant of formation of G(-H)* in dG was 1.7-fold larger in H2O than D2O, whereas the rate constant in the ODN duplex was 3.8-fold larger in H2O than D2O. These results suggest that the formation of G(-H)* from G+* in the ODN corresponds to the deprotonation of the oxidized hydrogen-bridged (G+*-C) base pair by a water molecule. The characteristic absorption maxima of G+* around 400 nm were shifted to a longer wavelength in the order of G<GG<GGG-containing ODNs. In contrast, the spectra of G(-H)* were not affected by the sequence and were essentially similar to that of free dG. These results suggest that the positive charge in G+* in ODN is delocalized over the extended pi orbitals of DNA base. The rate constant of the deprotonation was altered by the sequence of ODNs, where bases adjacent to guanine are important factors for deprotonation.
The non-self-complementary DNA decamer C-A-A-A-G-A-A-A-A-G/C-T-T-T-T-C-T-T-T-G is a DNA/DNA analogue of a portion of the polypurine tract or PPT, which is a RNA/DNA hybrid that serves as a primer for synthesis of the (+) DNA strand by HIV reverse transcriptase (RT), and which is not digested by the RNase H domain of reverse transcriptase following (-) strand synthesis. The same unusual conformation that eludes RNase H, thought to be a change in width of minor groove, may also be responsible for the inhibition of HIV RT by minor groove binding drugs such as distamycin and their bis-linked derivatives. The present X-ray crystal structure of this DNA decamer exhibits the usual properties of A-tract B-DNA under biologically relevant conditions: large propeller twist of base-pairs, narrowed minor groove, and a straight helix axis. Groove narrowing is fully developed in the A-A-A-A region, but not in the A-A-A region, which previous investigators have proposed as being too short to exhibit typical A-tract properties. The RNA/DNA hybrid produced by HIV reverse transcriptase during (-) strand synthesis presumably forms a "heteromerous" or H-helix with narrower minor groove than an A-helical RNA/RNA duplex. If the narrowing of minor groove in A-tract H-helices is comparable to that seen in A-tract B-helices, then the narrowed minor groove of the polypurine tract could make the second primer site both (1) impervious to RNase H digestion, and (2) susceptible to inhibition by minor groove binding drugs.
Many experiments have been done to determine how far and how freely holes can move along the stack of base pairs in DNA. The results of these experiments are usually described in terms of a parameter β under the assumption that it describes an exponential decay with distance. The reported values range from β < 0.2/Å to β > 1.4/Å. For the larger values of β, the transport can be accounted for as single step superexchange-mediated hole transfer. To account for the smaller values, hopping models have been proposed, the simplest being nearest-neighbor hopping. This model assumes that, between hops, the hole is localized on a single base with no overlap to neighbors. Noting that an electron or hole added to a DNA stack, as to other essentially one-dimensional entities, should distort its structure to form a polaron, Schuster and coworkers [Henderson, P. T., Jones, D., Hampikian, G., Kan, Y. and Schuster, G. B. (1999) Proc. Natl. Acad. Sci. USA 96, 8353-8358 and Ly, D., Sanii, L. and Schuster, G. B. (1999) J. Am. Chem. Soc. 121, 9400- 9410] proposed that transport occurs by polaron hopping between sites having approximately equal energies as a result of overlap. A recent experimental determination by Wan et al. [Wan, C., Fiebig, T., Kelley, S. O., Treadway, C. R., Barton, J. K. and Zewail, A. H. (1999) Proc. Natl. Acad. Sci. USA 96, 6014-6019] of the time required for an injected hole on DNA to travel a known distance leads to a large value of the diffusion constant. From this constant, a mobility of 0.2 cm2/V·s was deduced, orders of magnitude larger than typical hopping mobilities. We suggest that this ultrafast transport is due to polaron drift, which has been shown to lead to similar mobilities in chains of conjugated polymers. Using a simple model for the polaron, similar to that used for conjugated polymers such as polyacetylene, we show that, for reasonable values of the parameters, an injected electron or hole can form a polaron on a DNA stack.
The function of DNA during oxidative stress and its suitability as a potential building block for molecular devices depend on long-distance transfer of electrons and holes through the molecule, yet many conflicting measurements of the efficiency of this process have been reported. It is accepted that charges are transported over long distances through a multistep hopping reaction; this 'G-hopping' involves positive charges moving between guanines (Gs), the DNA bases with the lowest ionization potential. But the mechanism fails to explain the persistence of efficient charge transfer when the guanine sites are distant, where transfer rates do not, as expected, decrease rapidly with transfer distance. Here we show experimentally that the rate of charge transfer between two guanine bases decreases with increasing separation only if the guanines are separated by no more than three base pairs; if more bridging base pairs are present, the transfer rates exhibit only a weak distance dependence. We attribute this distinct change in the distance dependence of the rate of charge transfer through DNA to a shift from coherent superexchange charge transfer (tunnelling) at short distances to a process mediated by thermally induced hopping of charges between adenine bases (A-hopping) at long distances. Our results confirm theoretical predictions of this behaviour, emphasizing that seemingly contradictory observations of a strong as well as a weak influence of distance on DNA charge transfer are readily explained by a change in the transfer mechanism.
The dynamics of one-electron oxidation of guanine (G) base mononucleotide and that in DNA have been investigated by pulse radiolysis. The radical cation (G+*) of deoxyguanosine (dG), produced by oxidation with SO(4)-*, rapidly deprotonates to form the neutral G radical (G(-H)*) with a rate constant of 1.8 x 10(7) s(-1) at pH 7.0, as judged from transient spectroscopy. With experiments using different double-stranded oligonucleotides containing G, GG, and GGG sequences, the absorbance increases at 625 nm, characteristic of formation of the G(-H)*, were found to consist of two phases. The rate constants of the faster ( approximately 1.3 x 10(7) s(-1)) and slower phases ( approximately 3.0 x 10(6) s(-1)) were similar for the different oligonucleotides. On the other hand, in the oligonucleotide containing G located at the 5'- and 3'-terminal positions, only the faster phase was seen. These results suggest that the lifetime of the radical cation of the G:C base pair (GC+*), depending on its location in the DNA chain, is longer than that of free dG. In addition, the absorption spectral intermediates showed that hole transport to a specific G site within a 12-13mer double-stranded oligonucleotide is complete within 50 ns; that is, the rate of hole transport over 20 A is >10(7) s(-1).
Synthetic conjugates possessing bis(2-hydroxyethyl)stilbene-4,4'-diether linkers (Sd2) form the most stable DNA hairpins reported to date. Factors that affect stability are length and flexibility of the linkers and pi-stacking of the stilbene moiety on the adjacent base pair. The crystal structure of the hairpin d(GT(4)G)-Sd2-d(CA(4)C) was determined at 1.5 A resolution. The conformations of the two molecules in the asymmetric unit differ both in the linker and the stem portions. One of them shows a planar stilbene that is stacked on the adjacent G:C base pair. The other displays considerable rotation between the phenyl rings and an unprecedented edge-to-face orientation of stilbene and base pair. The observation of considerable variations in the conformation of the Sd moiety in the crystal structure allows us to exclude restriction of motion as the reason for the absence of Sd photoisomerization in the hairpins. Conformational differences in the stem portion of the two hairpin molecules go along with different Mg(2+) binding modes. Most remarkable among them is the sequence-specific coordination of a metal ion in the narrow A-tract minor groove. The crystal structure provides unequivocal evidence that a fully hydrated Mg(2+) ion can penetrate the narrow A-tract minor groove, causing the groove to further contract. Overall, the structural data provide a better understanding of the origins of hairpin stability and their photochemical behavior in solution.
The synthesis, steady-state spectroscopy, and transient absorption spectroscopy of DNA conjugates possessing both stilbene electron donor and electron acceptor chromophores are described. These conjugates are proposed to form nicked DNA dumbbell structures in which a stilbenedicarboxamide acceptor and stilbenediether donor are separated by variable numbers of A-T or G-C base pairs. The nick is located either adjacent to one of the chromophores or between two of the bases. Thermal dissociation profiles indicate that stable structures are formed possessing as few as two A-T base pairs. Circular dichroism (CD) spectra in the base pair region are characteristic of B-DNA duplex structures, whereas CD spectra at longer wavelengths display two bands attributed to exciton coupling between the two stilbenes. The sign and intensity of these bands are dependent upon both the distance between the chromophores and the dihedral angle between their transition dipoles [Deltaepsilon approximately Rda(-2) sin(2theta)]. Pulsed laser excitation of the stilbenediamide results in creation of the acceptor-donor radical ion pair, which decays via charge recombination. The dynamics of charge separation and charge recombination display an exponential distance dependence, similar to that observed previously for systems in which guanine serves as the electron donor. Unlike exciton coupling between the stilbenes, there is no apparent dependence of the charge-transfer rates upon the dihedral angle between donor and acceptor stilbenes. The introduction of a single G-C base pair between the donor and acceptor results in a change in the mechanism for charge separation from single step superexchange to hole hopping.
The mechanism and dynamics of photoinduced charge separation and charge recombination have been investigated in synthetic DNA hairpins possessing donor and acceptor stilbenes separated by one to seven A:T base pairs. The application of femtosecond broadband pump-probe spectroscopy, nanosecond transient absorption spectroscopy, and picosecond fluorescence decay measurements permits detailed analysis of the formation and decay of the stilbene acceptor singlet state and of the charge-separated intermediates. When the donor and acceptor are separated by a single A:T base pair, charge separation occurs via a single-step superexchange mechanism. However, when the donor and acceptor are separated by two or more A:T base pairs, charge separation occurs via a multistep process consisting of hole injection, hole transport, and hole trapping. In such cases, hole arrival at the electron donor is slower than hole injection into the bridging A-tract. Rate constants for charge separation (hole arrival) and charge recombination are dependent upon the donor-acceptor distance; however, the rate constant for hole injection is independent of the donor-acceptor distance. The observation of crossover from a superexchange to a hopping mechanism provides a "missing link" in the analysis of DNA electron transfer and requires reevaluation of the existing literature for photoinduced electron transfer in DNA.
Gute Übereinstimmung: Die Kinetik des photoinduzierten Lochtransports über DNA-A-Bereiche mit 1–7 Basenpaaren wurde durch transiente Femtosekundenabsorptionsspektroskopie bestimmt. Die Werte sind bei bis zu vier Basenpaaren stark entfernungsabhängig, bei größeren Abständen dann aber kaum noch. Diese Kinetik-Ergebnisse (□, ▪) stimmen sehr gut mit den DNA-Strangbruchergebnissen von Giese et al. (○, •) überein.
This work reports ESR studies that identify the favored site of deprotonation of the guanine cation radical (G*+) in an aqueous medium at 77 K. Using ESR and UV-visible spectroscopy, one-electron oxidized guanine is investigated in frozen aqueous D2O solutions of 2'-deoxyguanosine (dGuo) at low temperatures at various pHs at which the guanine cation radical, G*+ (pH 3-5), singly deprotonated species, G(-H)* (pH 7-9), and doubly deprotonated species, G(-2H)*- (pH > 11), are found. C-8-deuteration of dGuo to give 8-D-dGuo removes the major proton hyperfine coupling at C-8. This isolates the anisotropic nitrogen couplings for each of the three species and aids our analyses. These anisotropic nitrogen couplings were assigned to specific nitrogen sites by use of 15N-substituted derivatives at N1, N2, and N3 atoms in dGuo. Both ESR and UV-visible spectra are reported for each of the species: G*+, G(-H)*, and G(-2H)*-. The experimental anisotropic ESR hyperfine couplings are compared to those obtained from DFT calculations for the various tautomers of G(-H)*. Using the B3LYP/6-31G(d) method, the geometries and energies of G*+ and its singly deprotonated state in its two tautomeric forms, G(N1-H)* and G(N2-H)*, were investigated. In a nonhydrated state, G(N2-H)* is found to be more stable than G(N1-H)*, but on hydration with seven water molecules G(N1-H)* is found to be more stable than G(N2-H)*. The theoretically calculated hyperfine coupling constants (HFCCs) of G*+, G(N1-H)*, and G(-2H)*- match the experimentally observed HFCCs best on hydration with seven or more waters. For G(-2H)*-, the hyperfine coupling constant (HFCC) at the exocyclic nitrogen atom (N2) is especially sensitive to the number of hydrating water molecules; good agreement with experiment is not obtained until nine or 10 waters of hydration are included.