Katrin Tanzer

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.

Stability of the Parent Anion of the Potential Radiosensitizer 8-Bromoadenine Formed by Low-Energy (<3 eV) Electron Attachment

8-Bromoadenine (8BrA) is a potential DNA radiosensitizer for cancer radiation therapy due to its efficient interaction with low-energy electrons (LEEs). LEEs are a short-living species generated during the radiation damage of DNA by high-energy radiation as it is applied in cancer radiation therapy. Electron attachment to 8BrA in the gas phase results in a stable parent anion below 3 eV electron energy in addition to fragmentation products formed by resonant exocyclic bond cleavages. Density functional theory (DFT) calculations of the 8BrA- anion reveal an exotic bond between the bromine and the C8 atom with a bond length of 2.6 Å, where the majority of the charge is located on bromine and the spin is mainly located on the C8 atom. The detailed understanding of such long-lived anionic states of nucleobase analogues supports the rational development of new therapeutic agents, in which the enhancement of dissociative electron transfer to the DNA backbone is critical to induce DNA strand breaks in cancerous tissue.

Dissociative electron attachment to the gas-phase nucleobase hypoxanthine

We present high-resolution measurements of the dissociative electron attachment (DEA) to isolated gas-phase hypoxanthine (C5H4N4O, Hyp), a tRNA purine base. The anion mass spectra and individual ion efficiency curves from Hyp were measured as a function of electron energy below 9 eV. The mass spectra at 1 and 6 eV exhibit the highest anion yields, indicating possible common precursor ions that decay into the detectable anionic fragments. The (Hyp - H) anion (C5H3N4O(-)) exhibits a sharp resonant peak at 1 eV, which we tentatively assign to a dipole-bound state of the keto-N1H,N9H tautomer in which dehydrogenation occurs at either the N1 or N9 position based upon our quantum chemical computations (B3LYP/6-311+G(d,p) and U(MP2-aug-cc-pVDZ+)) and prior studies with adenine. This closed-shell dehydrogenated anion is the dominant fragment formed upon electron attachment, as with other nucleobases. Seven other anions were also observed including (Hyp - NH)(-), C4H3N4 (-)/C4HN3O(-), C4H2N3 (-), C3NO(-)/HC(HCN)CN(-), OCN(-), CN(-), and O(-). Most of these anions exhibit broad but weak resonances between 4 and 8 eV similar to many analogous anions from adenine. The DEA to Hyp involves significant fragmentation, which is relevant to understanding radiation damage of biomolecules.

Electron ionization of different large perfluoroethers embedded in ultracold helium droplets: effective freezing of short-lived decomposition intermediates

RATIONALE Electron ionization of three perfluoroethers (PFEs), C(6)F(14)O(3), C(8)F(18)O(4), and C(10)F(20)O(5), is studied in the gas phase and when the molecules are embedded in ultracold helium (He) droplets. The molecules investigated are model compounds for perfluoropolyethers used as lubricants in technical applications. The present study gives insight into possible radiolysis pathways upon radiation exposure. METHODS The experiments utilized a crossed electron/droplet beam apparatus consisting of a He droplet source and pick-up chamber combined with a commercial time-of-flight mass spectrometer. The doped droplets were ionized by electron ionization at 70 eV. RESULTS The He environment strongly affects the ionization patterns in the way that both the molecular ion M(+) and high-mass fragment ions formed by the loss of light neutral species such as F([M-F](+)), or CF(3)OCF(2) ([M-CF(3)OCF(2)](+)), etc., became strong signals in the mass spectrum. These signals were not or only barely visible in the gas-phase experiment and were identified as short lived (< µs) dissociation intermediates which in the gas phase immediately decomposed into lower-mass fragment ions. CONCLUSIONS Ionic fragmentation intermediates are frozen and subsequently stabilized in the He environment. Helium droplets can hence be viewed as a cryogenic laboratory transforming short-lived decomposition intermediates into stable fragment ions appearing as strong signals in the mass spectrum.

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 (8Br A). These results were evaluated against DEA measurements with isolated 8Br A 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.

Reactions in Nitroimidazole and Methylnitroimidazole Triggered by Low-Energy (0-8 eV) Electrons.

Low-energy electrons (0-8 eV) effectively decompose 4-nitroimidazole (4NI) and the two methylated isomers 1-methyl-5-nitroimidazole and 1-methyl-4-nitroimidazole via dissociative electron attachment (DEA). The involved unimolecular decompositions range from simple bond cleavages (loss of H(•), formation of NO2(-)) to complex reactions possibly leading to a complete degradation of the target molecule (formation of CN(-), etc.). At energies below 2 eV, the entire rich chemistry induced by DEA is completely quenched by methylation, as demonstrated in a previous communication (Tanzer, K.; Feketeová, L.; Puschnigg, B.; Scheier, P.; Illenberger. E.; Denifl, S. Angew. Chem., Int. Ed. 2014, 53, 12240). The observation that in 4NI neutral radicals and radical anions are formed via DEA at high efficiency already at threshold (0 eV) may have significant implications for the development of nitroimidazole-based radiosensitizers in tumor radiation therapy.

Low energy electron attachment to cyanamide (NH2CN)

Cyanamide (NH2CN) is a molecule relevant for interstellar chemistry and the chemical evolution of life. In the present investigation, dissociative electron attachment to NH2CN has been studied in a crossed electron-molecular beams experiment in the electron energy range from about 0 eV to 14 eV. The following anionic species were detected: NHCN(-), NCN(-), CN(-), NH2(-), NH(-), and CH2(-). The anion formation proceeds within two broad electron energy regions, one between about 0.5 and 4.5 eV and a second between 4.5 and 12 eV. A discussion of possible reaction channels for all measured negative ions is provided. The experimental results are compared with calculations of the thermochemical thresholds of the anions observed. For the dehydrogenated parent anion, we explain the deviation between the experimental appearance energy of the anion with the calculated corresponding reaction threshold by electron attachment to the isomeric form of NH2CN--carbodiimide.

Dissociative electron attachment to the radiosensitizing chemotherapeutic agent hydroxyurea

Dissociative electron attachment to hydroxyurea was studied in the gas phase for electron energies ranging from zero to 9 eV in order to probe its radiosensitizing capabilities. The experiments were carried out using a hemispherical electron monochromator coupled with a quadrupole mass spectrometer. Diversified fragmentation of hydroxyurea was observed upon low energy electron attachment and here we highlight the major dissociation channels. Moreover, thermodynamic thresholds for various fragmentation reactions are reported to support the discussion of the experimental findings. The dominant dissociation channel, which was observed over a broad range of energies, is associated with formation of NCO(-), water, and the amidogen (NH2) radical. The second and third most dominant dissociation channels are associated with formation of NCNH(-) and NHCONH2 (-), respectively, which are both directly related to formation of the highly reactive hydroxyl radical. Other ions observed with significant abundance in the mass spectra were NH2 (-)/O(-), OH(-), CN(-), HNOH(-), NCONH2 (-), and ONHCONH2 (-).

Fragmentation patterns of 4(5)-nitroimidazole and 1-methyl-5-nitroimidazole—The effect of the methylation

We present here the photofragmentation patterns of doubly ionized 4(5)-nitroimidazole and 1-methyl-5-nitroimidazole. The doubly ionized state was created by core ionizing the C 1s orbitals of the samples, rapidly followed by Auger decay. Due to the recent development of nitroimidazole-based radiosensitizing drugs, core ionization was selected as it represents the very same processes taking place under the irradiation with medical X-rays. In addition to the fragmentation patterns of the sample, we study the effects of methylation on the fragmentation patterns of nitroimidazoles. We found that methylation alters the fragmentation significantly, especially the charge distribution between the final fragments. The most characteristic feature of the methylation is that it effectively quenches the production of NO and NO+ , widely regarded as key radicals in the chemistry of radiosensitization by the nitroimidazoles.

High Resolution Electron Attachment to Water Clusters in Helium Droplets

We have determined the resonance energies for free electron (up to 3eV) attachment to water clusters embedded in helium droplets. In comparison to pure water clusters, shifts and broadening of the resonance features were observed, which shows a pronounced dependence on the water cluster anion size.