Resonant Formation of Strand Breaks in Sensitized Oligonucleotides Induced by Low‐Energy Electrons (0.5–9 eV)

Halogenated nucleobases are used as radiosensitizers in cancer radiation therapy, enhancing the reactivity of DNA to secondary low‐energy electrons (LEEs). LEEs induce DNA strand breaks at specific energies (resonances) by dissociative electron attachment (DEA). Although halogenated nucleobases show intense DEA resonances at various electron energies in the gas phase, it is inherently difficult to investigate the influence of halogenated nucleobases on the actual DNA strand breakage over the broad range of electron energies at which DEA can take place (<12 eV). By using DNA origami nanostructures, we determined the energy dependence of the strand break cross‐section for oligonucleotides modified with 8‐bromoadenine (^8BrA). These results were evaluated against DEA measurements with isolated ^8BrA in the gas phase. Contrary to expectations, the major contribution to strand breaks is from resonances at around 7 eV while resonances at very low energy (<2 eV) have little influence on strand breaks.     

Dissociative electron attachment to gas phase valine: a combined experimental and theoretical study

Using a crossed electron/molecule beam technique the dissociative electron attachment (DEA) to gas phase L-valine, (CH(3))(2)CHCH(NH(2))COOH, is studied by means of mass spectrometric detection of the product anions. Additionally, ab initio calculations of the structures and energies of the anions and neutral fragments have been carried out at G2MP2 and B3LYP levels. Valine and the previously studied aliphatic amino acids glycine and alanine exhibit several common features due to the fact that at low electron energies the formation of the precursor ion can be characterized by occupation of the pi* orbital of the carboxyl group. The dominant negative ion (M-H)(-) (m/Z=116) is observed at electron energies of 1.12 eV. This ion is the dominant reaction product at electron energies below 5 eV. Additional fragment ions with m/Z=100, 72, 56, 45, 26, and 17 are observed both through the low lying pi* and through higher lying resonances at about 5.5 and 8.0-9.0 eV, which are characterized as core excited resonances. According to the threshold energies calculated here, rearrangements play a significant role in the formation of DEA fragments observed from valine at subexcitation energies.     

Reactions in Nitroimidazole Triggered by Low‐Energy (0–2 eV) Electrons: Methylation at N1‐H Completely Blocks Reactivity

Low‐energy electrons (LEEs) at energies of less than 2 eV effectively decompose 4‐nitroimidazole (4NI) by dissociative electron attachment (DEA). The reactions include simple bond cleavages but also complex reactions involving multiple bond cleavages and formation of new molecules. Both simple and complex reactions are associated with pronounced sharp features in the anionic yields, which are interpreted as vibrational Feshbach resonances acting as effective doorways for DEA. The remarkably rich chemistry of 4NI is completely blocked in 1‐methyl‐4‐nitroimidazole (Me4NI), that is, upon methylation of 4NI at the N1 site. These remarkable results have also implications for the development of nitroimidazole based radiosensitizers in tumor radiation therapy.     

Vibrational Feshbach resonances in uracil and thymine

Sharp peaks in the dissociative electron attachment (DEA) cross sections of uracil and thymine at energies below 3 eV are assigned to vibrational Feshbach resonances (VFRs) arising from coupling between the dipole bound state and the temporary anion state associated with occupation of the lowest sigma* orbital. Three distinct vibrational modes are identified, and their presence as VFRs is consistent with the amplitudes and bonding characteristics of the sigma* orbital wave function. A deconvolution method is also employed to yield higher effective energy resolution in the DEA spectra. The site dependence of DEA cross sections is evaluated using methyl substituted uracil and thymine to block H atom loss selectively. Implications for the broader issue of DNA damage are briefly discussed.     

Functional group dependent dissociative electron attachment to simple organic molecules

Dissociative electron attachment (DEA) cross sections for simple organic molecules, namely, acetic acid, propanoic acid, methanol, ethanol, and n-propyl amine are measured in a crossed beam experiment. We find that the H(-) ion formation is the dominant channel of DEA for these molecules and takes place at relatively higher energies (>4 eV) through the core excited resonances. Comparison of the cross sections of the H(-) channel from these molecules with those from NH(3), H(2)O, and CH(4) shows the presence of functional group dependence in the DEA process. We analyze this new phenomenon in the context of the results reported on other organic molecules. This discovery of functional group dependence has important implications such as control in electron induced chemistry and understanding radiation induced damage in biological systems.     

Sensitizing DNA Towards Low‐Energy Electrons with 2‐Fluoroadenine

2‐Fluoroadenine (^2FA) is a therapeutic agent, which is suggested for application in cancer radiotherapy. The molecular mechanism of DNA radiation damage can be ascribed to a significant extent to the action of low‐energy (<20 eV) electrons (LEEs), which damage DNA by dissociative electron attachment. LEE induced reactions in ^2FA are characterized both isolated in the gas phase and in the condensed phase when it is incorporated into DNA. Information about negative ion resonances and anion‐mediated fragmentation reactions is combined with an absolute quantification of DNA strand breaks in ^2FA‐containing oligonucleotides upon irradiation with LEEs. The incorporation of ^2FA into DNA results in an enhanced strand breakage. The strand‐break cross sections are clearly energy dependent, whereas the strand‐break enhancements by ^2FA at 5.5, 10, and 15 eV are very similar. Thus, ^2FA can be considered an effective radiosensitizer operative at a wide range of electron energies.     

Shape and core‐excited resonances of thionucleobases

Thionucleobases can be used in chemoradiation therapy of cancer. Shape resonances (SRs) and core‐excited resonances (CERs) can lead to fragmentation and eventually result in strand breaks of DNA. In particular, the more energetic CERs are believed to cause double‐strand breaks that can hardly be repaired. In this work, both the SRs and CERs of exemplary 2‐thiouracil, 4‐thiouracil, 2‐thiothymine, 4‐thiothymine, and 6‐aza‐2‐thiothymine are investigated using stabilization method in conjunction with long range corrected time‐dependent density functional theory. Results indicate that the energies of (1) π*₁ and π*₂ SRs, (2) n‐π* CERs, and (3) mixed resonances of π‐π* CERs with π* SRs can be significantly stabilized due to thionation of uracil or thymine. It is noteworthy that the resonant cases of (2) and (3) can be accessed by electrons even at energies below 4 eV. Consequently, the increased decay of temporary anions can enhance strand breaks of DNA.     

Low energy electron-induced reactions in gas phase 1,2,3,5-tetra-O-acetyl-beta-D-ribofuranose: a model system for the behavior of sugar in DNA

Dissociative electron attachment to 1,2,3,5-tetra-O-acetyl-beta-D-ribofuranose (TAR) is studied in a crossed electron-molecular beam experiment with mass spectrometric detection of the observed fragment ions. Since in TAR acetyl groups are coupled at the relevant positions to the five membered ribose ring, it may serve as an appropriate model compound to study the response of the sugar unit in DNA towards low energy electrons. Intense resonances close to 0 eV are observed similar to the pure gas phase sugars (2-deoxyribose, ribose, and fructose). Further strong resonances appear in the range of 1.6-1.8 eV (not present in the pure sugars). Based on calculations on transient anions adopting the stabilization method, this feature is assigned to a series of closely spaced shape resonances of pi* character with the extra electron localized on the acetyl groups outside the ribose ring system. Further but weaker resonant contributions are observed in the range of 7-11 eV, representing core excited resonances and/or sigma* shape resonances. The decomposition processes involve single bond ruptures but also more complex reactions associated with substantial rearrangement. The authors hence propose that the sugar unit in DNA plays an active role in the molecular mechanism towards single strand breaks induced by low energy electrons.     

Strong fragmentation processes driven by low energy electron attachment to various small perfluoroether molecules

Negative ion formation in the three perfluoroethers (PFEs) diglyme (C(6)F(14)O(3)), triglyme (C(8)F(18)O(4)) and crownether (C(10)F(20)O(5)) is studied following electron attachment in the range from ～0 to 15?eV. All three compounds show intense low energy resonances at subexcitation energies (<3?eV) decomposing into a variety of negatively charged fragments. These fragment ions are generated via dissociative electron attachment (DEA), partly originating from sequential decompositions on the metastable (μs) time scale as observed from the MIKE (metastable induced kinetic energy) scans. Only in perfluorocrownether a signal due to the non-decomposed parent anion is observed. Additional and comparatively weaker resonances are located in the energy range between ～10 and 17?eV which preferentially decompose into lighter ions. It is suggested that specific features of perfluoropolyethers (PFPEs) relevant in applications, e.g., the strong bonding to surfaces induced by UV radiation of the substrate or degradation of PFPE films in computer hard disc drives can be explained by their pronounced sensitivity towards low energy electrons.     

Vibrational and electronic excitation in p-benzoquinone by electron impact

Vibrational and electronic excitation by electron impact in p-benzoquinone was studied using a trochoidal electron spectrometer. Two distinct patterns of vibrational excitation were observed. First, low quanta of a few selected vibrations are specifically excited at incident electron energies corresponding to shape resonances. Some resonances excite mainly the CO stretch, others the CH stretch vibration, and this selectivity is used in the discussion of the assignment of the resonances. A second pattern is an unspecific excitation of a quasi-continuum where no structure due to individual vibrational levels can be discerned. This feature peaks at threshold, large amounts of vibrational energy can be deposited in the molecule, and the excitation also proceeds via shape resonances. Electronic excitation spectra in the valence and Rydberg regions are also presented and discussed. A band observed at 4.37 eV with low residual energies has been tentatively assigned to the second π — π* triplet state ³B_3g.     

Towards an Understanding of Halide Interactions with the Carbonyl-Containing Molecule CH3CHO

The anion photoelectron spectra of Cl⁻⋅⋅⋅CD₃CDO, Cl⁻⋅⋅⋅(CD₃CDO)₂, Br⁻⋅⋅⋅CH₃CHO, and I⁻⋅⋅⋅CH₃CHO are presented with electron stabilisation energies of 0.55, 0.93, 0.48, and 0.40 eV, respectively. Optimised geometries of the singly solvated species featured the halide appended to the CH₃CHO molecule in-line with the electropositive portion of the C=O bond and having binding energies between 45 and 52 kJ mol⁻¹. The doubly solvated Cl⁻⋅⋅⋅(CH₃CHO)₂ species features asymmetric solvation upon the addition of a second CH₃CHO molecule. Theoretical detachment energies were found to be in excellent agreement with experiment, with comparisons drawn between other halide complexes with simple carbonyl molecules.     

Dissociative electron attachment to furan, tetrahydrofuran, and fructose

We study dissociative electron attachment to furan (FN) (C(4)H(4)O), tetrahydrofuran (THF) (C(4)H(8)O), and fructose (FRU) (C(6)H(12)O(6)) using crossed electron/molecular beams experiments with mass spectrometric detection of the anions. We find that FN and THF are weak electron scavengers and subjected to dissociative electron attachment essentially in the energy range above 5.5 eV via core excited resonances. In striking contrast to that, FRU is very sensitive towards low energy electrons generating a variety of fragment ions via a pronounced low energy feature close to 0 eV. These reactions are associated with the degradation of the ring structure and demonstrate that THF cannot be used as surrogate to model deoxyribose in DNA with respect to the attack of electrons at subexcitation energies (<3 eV). The results support the picture that in DNA the sugar moiety itself is an active part in the initial molecular processes leading to single strand breaks.     

Phosphodiester and N-glycosidic bond cleavage in DNA induced by 4-15 eV electrons

Thin molecular films of the short single strand of DNA, GCAT, were bombarded under vacuum by electrons with energies between 4 and 15 eV. Ex vacuo analysis by high-pressure liquid chromatography of the samples exposed to the electron beam revealed the formation of a multitude of products. Among these, 12 fragments of GCAT were identified by comparison with reference compounds and their yields were measured as a function of electron energy. For all energies, scission of the backbone gave nonmodified fragments containing a terminal phosphate, with negligible amounts of fragments without the phosphate group. This indicates that phosphodiester bond cleavage by 4-15 eV electrons involves cleavage of the C-O bond rather than the P-O bond. The yield functions exhibit maxima at 6 and 10-12 eV, which are interpreted as due to the formation of transient anions leading to fragmentation. Below 15 eV, these resonances dominate bond dissociation processes. All four nonmodified bases are released from the tetramer, by cleavage of the N-glycosidic bond, which occurs principally via the formation of core-excited resonances located around 6 and 10 eV. The formation of the other nonmodified products leading to cleavage of the phosphodiester bond is suggested to occur principally via two different mechanisms: (1) the formation of a core-excited resonance on the phosphate unit followed by dissociation of the transient anion and (2) dissociation of the CO bond of the phosphate group formed by resonance electron transfer from the bases. In each case, phosphodiester bond cleavage leads chiefly to the formation of stable phosphate anions and sugar radicals with minimal amounts of alkoxyl anions and phosphoryl radicals.     

Single,double, and multiple double strand breaks induced in DNA by 3-100 eV electrons

Nonthermal secondary electrons with initial kinetic energies below 100 eV are an abundant transient species created in irradiated cells and thermalize within picoseconds through successive multiple energy loss events. Here we show that below 15 eV such low-energy electrons induce single (SSB) and double (DSB) strand breaks in plasmid DNA exclusively via formation and decay of molecular resonances involving DNA components (base, sugar, hydration water, etc.). Furthermore, the strand break quantum yields (per incident electron) due to resonances occur with intensities similar to those that appear between 25 and 100 eV electron energy, where nonresonant mechanisms related to excitation/ionizations/dissociations are shown to dominate the yields, although with some contribution from multiple scattering electron energy loss events. We also present the first measurements of the electron energy dependence of multiple double strand breaks (MDSB) induced in DNA by electrons with energies below 100 eV. Unlike the SSB and DSB yields, which remain relatively constant above 25 eV, the MDSB yields show a strong monotonic increase above 30 eV, however with intensities at least 1 order of magnitude smaller than the combined SSB and DSB yields. The observation of MDSB above 30 eV is attributed to strand break clusters (nano-tracks) involving multiple successive interactions of one single electron at sites that are distant in primary sequence along the DNA double strand, but are in close contact; such regions exist in supercoiled DNA (as well as cellular DNA) where the double helix crosses itself or is in close proximity to another part of the same DNA molecule.     

Metastable anions of dinitrobenzene: resonances for electron attachment and kinetic energy release

Attachment of free, low-energy electrons to dinitrobenzene (DNB) in the gas phase leads to DNB(-) as well as several fragment anions. DNB(-), (DNB-H)(-), (DNB-NO)(-), (DNB-2NO)(-), and (DNB-NO(2))(-) are found to undergo metastable (unimolecular) dissociation. A rich pattern of resonances in the yield of these metastable reactions versus electron energy is observed; some resonances are highly isomer-specific. Most metastable reactions are accompanied by large average kinetic energy releases (KER) that range from 0.5 to 1.32 eV, typical of complex rearrangement reactions, but (1,3-DNB-H)(-) features a resonance with a KER of only 0.06 eV for loss of NO. (1,3-DNB-NO)(-) offers a rare example of a sequential metastable reaction, namely, loss of NO followed by loss of CO to yield C(5)H(4)O(-) with a large KER of 1.32 eV. The G4(MP2) method is applied to compute adiabatic electron affinities and reaction energies for several of the observed metastable channels.     

Relation between electron scattering resonances of isolated NTCDA molecules and maxima in the density of unoccupied states of condensed NTCDA layers

The empty-level structure of the 1,4,5,8-naphthalenetetracarboxylic dianhydride (NTCDA) molecule is characterized by means of dissociative electron attachment (DEA) experiments in the gas phase coupled with DFT calculations. Distinct maxima in the anion currents generated by electron attachment to NTCDA, as a function of incident electron energy, are ascribed to capture of incident electrons into empty orbitals, i.e., the process referred to as shape resonance. The empty orbital energies of gas-phase NTCDA shifted to 1.2 eV lower energy reproduce satisfactorily the maxima of the unoccupied electronic states of a multilayer NTCDA film measured by means of the very low energy electron diffraction method and the total current spectroscopy measurement scheme. The present results indicate that the empty levels of individual NTCDA molecules are stabilized in the solid state, but their relative energies remain nearly unaltered. The stabilization energy in multilayer film of NTCDA molecules is likely due to attractive polarization forces. Fragmentation of the gas-phase NTCDA temporary parent anions via the DEA mechanism, the other issue of the present investigation, leads to the rupture of the bonds between the end carbonyl groups and the naphthalene core, and occurs at incident electron energies above 2 eV. Possible chemical changes in condensed NTCDA molecules initiated by the DEA mechanism under conditions of electron transport through the film are discussed.     

Enhancements in dissociative electron attachment to CF4, chlorofluorocarbons and hydrochlorofluorocarbons adsorbed on H2O ice

We report that the absolute cross sections for dissociative attachment of approximately 0 eV electrons to chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs) are strongly enhanced by the presence of H2O ice. The absolute cross sections for CFCl3, CHF2Cl, and CH3CF2Cl on water ice are measured to be approximately 8.9 x 10(-14), approximately 5.1 x 10(-15), and approximately 4.9 x 10(-15) cm2 at approximately 0 eV, respectively. The former value is about 1 order of magnitude higher than that in the gas phase, while the latter two are 3-4 orders higher. In contrast, the resonances at electron energies > or = 2.0 eV are strongly suppressed either for CFCs and HCFCs or for CF4 adsorbed on H2O ice. The cross-section enhancement is interpreted to be due to electron transfer from precursor states of the solvated electron in ice to an unfilled molecular orbital of CFCs or HCFCs followed by its dissociation. This study indicates that electron-induced dissociation is a significant process leading to CFC and HCFC fragmentation on ice surfaces.     

Phenol, chlorobenzene and chlorophenol isomers: resonant states and dissociative electron attachment

This paper reports a study of resonant dissociative electron attachment (DEA) to the phenol, chlorobenzene, p-, m-, and o-chlorophenol molecules. On the basis of spectroscopic and thermochemical approaches the resonant states of the molecular negative ions (NIs) and the structures of some dissociative decay products are assigned. In the electron energy range up to 3 eV, DEA processes are determined by the two 2[pi*]-shape resonances resulting mainly in formation of [M-H]- and/or Cl- ions. At higher electron energies the energy correlation between peaks in the negative ion effective yield curves and bands of UV spectra allowed identification of the core-excited resonances. The peculiarities of Cl- ion formation and the vibrational fine structure on the effective yield curves of the [M-H]- ions are discussed. The mass spectrometric procedures for measurement of relative cross sections for NI formation are described.     

Degradation of vitamin C by low-energy electrons

We report on the degradation of gas phase vitamin C (ascorbic acid, AA) induced by low-energy electrons. In the energy range of (0–12) eV, different negatively charged fragments, attributed to the dehydro-ascorbic acid anion ((AA–H)⁻), OH⁻, O⁻ and H⁻, are observed. The yield functions indicate that these ions are formed via dissociative electron attachment, DEA. While the formation of (AA–H)⁻ is exclusively observed at sub-excitation energies (<1.5 eV), the other fragments arise from resonance features at higher energies. Possible implications of these observations for radiation damage and food treatment by high energy radiation are considered.     

Collisional dissociation of CH2Br+2 in selected internal energy states

The collisionally induced dissociation of CH₂Br⁺₂ to yield CH₂Br⁺ + Br has been investigated by photoelectronphotoion coincedence spectroscopy in which nominally zero kinetic electrons were detected. The reactant CH₂Br⁺₂ ions were produced by photoionzation with intenal energies of 0.0, 0.20 and 0.60 eV. For all three internal energies, the kinetic energy threshold for dissociation is just equal to the energy defect.