Michael A. Huels

RESONANT DISSOCIATION OF DNA BASES BY SUBIONIZATION ELECTRONS

We have measured the electron energy dependence for production of a great variety of anion fragments, induced by resonant attachment of subionization electrons to thymine (T) and cytosine (C) within femto-second time scales. At the lowest electron energies we also observe stable molecular anions of these bases, viz., T− and C−. Our measurements suggest that this resonant mechanism may relate to critical damage of irradiated cellular DNA by subionization electrons prior to thermalization.

Cross Sections for Low-Energy (10 – 50 eV) Electron Damage to DNA

Abstract Boudaïffa, B., Cloutier, P., Hunting, D., Huels, M. A. and Sanche, L. Cross Sections for Low-Energy (10 – 50 eV) Electron Damage to DNA. Radiat. Res. 157, 227 – 234 (2002). We report direct measurements of the formation of single-, double- and multiple strand breaks in pure plasmid DNA as a function of exposure to 10 – 50 eV electrons. The effective cross sections to produce these different types of DNA strand breaks were determined and were found to range from approximately 10−17 to 3  × 10−15 cm2. The total effective cross section and the effective range for destruction of supercoiled DNA extend from 3.4 to 4.4  × 10−15 cm2 and 12 to 14 nm, respectively, over the range 10 – 50 eV. The variation of the effective cross sections with electron energy is discussed in terms of the electrons inelastic mean free path, penetration depth, and dissociation mechanisms, including resonant electron capture; the latter is found to dominate the effective cross sections for single- and double-strand breaks at 10 eV. The most striking observations are that (1) supercoiled DNA is approximately one order of magnitude more sensitive to the formation of double-strand breaks by low-energy electrons than is relaxed circular DNA, and (2) the dependence of the effective cross sections on the incident electron energy is unrelated to the corresponding ionization cross sections. This finding suggests that the traditional notion that radiobiological damage is related to the number of ionization events would not apply at very low energies.

Formation of anion fragments from gas-phase glycine by low energy (0–15 eV) electron impact

We have measured the formation of anion fragments in gas phase glycine (H2NCH2COOH) via dissociative electron attachment (DEA) reactions in the 0–15 eV electron energy range, using a monochromatic electron beam and mass spectrometric detection of the negative ions. By far the most intense product observed is the closed shell glycine anion (H2NCH2COO)− which appears from a low-energy resonance with a peak located at 1.4 eV and a cross section in the range 10−16 cm2. The corresponding precursor ion can be characterized by electron attachment into the empty π* orbital of the −COOH group as recently assigned from electron transmission experiments and ab initio self-consistent field calculations [Aflatooni, Hitt, Gallup, and Burrow, J. Chem. Phys. 115, 6489 (2001)]. This precursor state is also observed to decompose (with much lower intensity) yielding a negative ion fragment with 58 amu, which is attributed to anions of the stoichiometric composition H2C2O2− or H4C2NO−. A further prominent DEA peak is observe...

Dissociative electron attachment to gas-phase 5-bromouracil

We report measurements of dissociative electron attachment (DEA) to gaseous 5-bromouracil (BrU) for incident electron energies between 0 and 16 eV. Low energy electron impact on BrU leads not only to the formation of a long lived parent anion BrU−, but also various anion fragments resulting from endo- and exo-cyclic bond ruptures, such as Br−, uracil-yl anions, i.e., (U-yl)−, OCN−, and a 68 amu anion tentatively attributed to H2C3NO−. The incident electron energy dependent signatures of either the Br− and (U-yl)− yields (at 0, 1.4, and 6 eV), or the OCN− and H2C3NO− yields (at 1.6 and 5.0 eV) suggests competing DEA channels for anion fragment formation. The production cross sections, at 0 eV incident electron energy, for BrU−, Br−, and (U-yl)− are estimated to be about 6×10−15, 6×10−14, and 1.0×10−15 cm2, respectively.

Halogen anion formation in 5-halouracil films: X rays compared to subionization electrons.

The radiosensitization properties of 5-halouracils (5-FU, 5-BrU and 5-IU), i.e. the enhanced sensitivity of biological media containing these compounds to ionizing radiation, have been studied using surface science methods. We show that soft X rays and near 0 eV electrons both induce dissociation of 5-halouracils into a halogen anion and a uracilyl radical. The yield of anions from 5-FU is much smaller than that from the bromo- and iodo-analogs. We explain the high anion yields in 5-BrU and 5-IU with dissociative electron attachment (DEA) of near 0 eV electrons. The thermodynamic threshold for DEA to 5-FU is near 2 eV and therefore prohibits dissociation by near 0 eV electrons.

Single-Strand-Specific Radiosensitization of DNA by Bromodeoxyuridine

Abstract Cecchini, S., Girouard, S., Huels, M. A., Sanche, L. and Hunting, D. J. Single-Strand-Specific Radiosensitization of DNA by Bromodeoxyuridine. Radiat. Res. 162, 604–615 (2004). The effects of bromodeoxyuridine (BrdUrd) substitution for thymidine on γ-ray-induced strand breakage were determined in single- and double-stranded oligonucleotides and double-stranded oligonucleotides containing a mismatched bubble region. BrdUrd does not sensitize complementary double-stranded DNA to γ-ray-induced strand breakage, but it greatly sensitizes single-stranded DNA. However, when the BrdUrd is present in a single-stranded bubble of a double-stranded oligonucleotide, the non-base-paired nucleotides adjacent to the BrdUrd as well as several unpaired sites on the opposite unsubstituted strand are strongly sensitized. The radiosensitization properties of BrdUrd result primarily from the electrophilic nature of the bromine, making it a good leaving group and leading to the irreversible formation of the uridine-yl radical (dUrd·) or the uridine-yl anion (dUrd−) upon addition of an electron. The radiolytic loss of the bromine atom is greatly suppressed in double-stranded compared to single-stranded DNA. Thus we propose that the radiosensitization effects of bromouracil in vivo will likely be limited to single-strand regions such as found in transcription bubbles, replication forks, DNA bulges and the loop region of telomeres. Our results may have profound implications for the clinical use of bromodeoxyuridine (BrdUrd) as a radiosensitizer as well as for the development of targeted radiosensitizers.

Reactive scattering of O− in organic films at subionization collision energies

Anion desorption stimulated by the impact of 0–20 eV electrons on O2/hydrocarbon mixed films is reported. It is shown that part of the H−, OH−, CH−, and CH2− desorption yields from O2/hydrocarbon films is the result of reactive scattering of O− fragments produced via dissociative electron attachment (DEA) in the alkane and alkene thin films. These results support the interpretation that the DEA O− react with the hydrocarbon molecules to form a transient molecular anion complex which, in addition to autodetachment, may decay by dissociation into various anion and neutral fragments, and thus cause chemical modification of the solid.

Fragmentation dynamics of condensed phase thymine by low-energy (10-200 eV) heavy-ion impact.

We report measurements of the formation and desorption of ionic fragments induced by very low-energy (10-200 eV) Ar(+) irradiation of thymine (T) films, deposited on a polycrystalline Pt substrate. A multitude of dissociation channels is observed, among which the major cation species are identified as HNCH(+), HNC(3)H(4) (+), C(3)H(3) (+), OCNH(2) (+), [T-OCN](+), [T-OCNH(2)](+), [T-O](+), and [T+H](+) and the major anions as H(-), O(-), CN(-),and OCN(-). Cation fragment desorption appears at much lower threshold energies (near 15 eV) than anion fragment desorption, where the latter depends strongly on the film thickness. It is proposed that anion fragment formation and desorption results from projectile impact-induced excitation of either (1) a neutral thymine molecule, followed by fragmentation and charge exchange between the energetic neutral fragment and the substrate (or film) and/or (2) a deprotonated monoanionic thymine molecule to a dissociative state, followed by a unimolecular fragmentation of the excited thymine anion. The H(-) and O(-) fragment formations may have a further contribution from dipolar dissociation, e.g., formation of electronically excited neutral thymine, followed by dissociation into O(-)+[T-O](+), due to their reduced sensitivity to the film thickness. Positive-ion fragment desorption exhibits no significant dependence on film thickness before the emergence of surface charging, and originates from a kinetically assisted charge-transfer excitation. The results suggest that the potential energy of the incident ion plays a significant role in lowering the threshold energy of kinetic fragmentation of thymine. Measurements of the time-dependent film degradation yields for 100-eV Ar(+) suggest a quantum efficiency for degradation of about six thymine molecules per incident ion.

Electron stimulated desorption of O− and metastable CO* from physisorbed CO2

We report electron stimulated desorption (ESD) measurements of O− yields produced by dissociative electron attachment (DEA) to physisorbed CO2. The molecules are condensed at about 17–20 K on polycrystalline Pt, either as pure multilayer films, or in submonolayer (ML) quantities onto thick rare gas substrates. For the pure disordered multilayer solids, we observe four peaks in the O− yield function at incident electron energies, E(e), of about 4.1, 8.5, 11.2, and 15 eV. The lowest two are assigned, respectively, to the 2Πu and 2Πg resonance states of CO−2, which dissociate into O−(2P)+CO(X 1Σ+), and are known to dominate the gas phase DEA O− production cross section for E(e)≤20 eV. Measurements of ESD CO* metastable yields from similar CO2 multilayer solids on Pt(111), also presented here, suggest that the 11.2 and 15 eV O− peaks are associated with the manifold of close‐lying CO2*− states which dissociate into O−(2P)+CO* (a 3Π, a′ 3Σ+, or d 3Δ). For 0.15 ML of CO2 physisorbed on 20 ML thick rare gas subs...

Photofragmentation of 2-deoxy-D-ribose molecules in the gas phase

We have measured the synchrotron-induced photofragmentation of isolated 2-deoxy-D-ribose molecules (C(5)H(10)O(4)) at four photon energies, namely, 23.0, 15.7, 14.6, and 13.8 eV. At all photon energies above the molecules ionization threshold we observe the formation of a large variety of molecular cation fragments, including CH(3) (+), OH(+), H(3)O(+), C(2)H(3) (+), C(2)H(4) (+), CH(x)O(+) (x=1,2,3), C(2)H(x)O(+) (x=1-5), C(3)H(x)O(+) (x=3-5), C(2)H(4)O(2) (+), C(3)H(x)O(2) (+) (x=1,2,4-6), C(4)H(5)O(2) (+), C(4)H(x)O(3) (+) (x=6,7), C(5)H(7)O(3) (+), and C(5)H(8)O(3) (+). The formation of these fragments shows a strong propensity of the DNA sugar to dissociate upon absorption of vacuum ultraviolet photons. The yields of particular fragments at various excitation photon energies in the range between 10 and 28 eV are also measured and their appearance thresholds determined. At all photon energies, the most intense relative yield is recorded for the m/q=57 fragment (C(3)H(5)O(+)), whereas a general intensity decrease is observed for all other fragments- relative to the m/q=57 fragment-with decreasing excitation energy. Thus, bond cleavage depends on the photon energy deposited in the molecule. All fragments up to m/q=75 are observed at all photon energies above their respective threshold values. Most notably, several fragmentation products, for example, CH(3) (+), H(3)O(+), C(2)H(4) (+), CH(3)O(+), and C(2)H(5)O(+), involve significant bond rearrangements and nuclear motion during the dissociation time. Multibond fragmentation of the sugar moiety in the sugar-phosphate backbone of DNA results in complex strand lesions and, most likely, in subsequent reactions of the neutral or charged fragments with the surrounding DNA molecules.