Sanazole is a hypoxic radiosensitizer for which the activation mechanism in cells has been suggested to involve initial reduction. Herein, electron attachment to sanazole under isolated conditions and upon microhydrations is investigated. Employing mass spectrometry supported by quantum chemical calculations, the anion formation mechanism and subsequent fragmentation pathways are examined. In the case of electron attachment to the isolated molecule, predominantly dissociative electron attachment is observed. The most prominent fragment anion, (NTR-yl)- at m/z 113, is suggested to be formed in an exothermic pathway through a single-bond dissociation, whereas other intense fragments require structural reorganization. The limited abundance of the parent anion under isolated conditions is altered upon microhydration conditions since in the latter situation only the (microhydrated) parent anion is observed. This result suggests that hydration closes and/or slows down the dissociation process and indicates that for sanazole, the initial mechanism of action in a reductive cell environment may be similar to that of well-studied nitroimidazole radiosensitizers.

• Klíčová slova
• electron attachment, electron‐induced dissociation, radiosensitizer, sanazol,
• MeSH
• elektrony * MeSH
• hmotnostní spektrometrie MeSH
• radiosenzibilizující látky * chemie   MeSH
• triazoly * chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• radiosenzibilizující látky * MeSH
• triazoly * MeSH

Reactivity toward low-energy electrons (LEE) has been hypothesized as a cause of radio-modifying properties for various molecules. LEE's transient nature, however, prevents the establishment of clear links between initial processes at the sub-ps time scale and the final products of radiolysis. Here, such links are explored for the radio-modifying compound RRx-001 (1-bromoacetyl-3,3-dinitroazetidine). Picosecond pulse radiolysis demonstrates the high scavenging capacity of the molecule for secondary quasi-free and solvated electrons forming stable parent anions confirmed by studies of microsolvated RRx-001 in clusters. The anions decay either via auto-detachment of an electron or dissociate involving hydrogen transfer from solvent, resulting in NO2 and 1-(bromoacetyl)-3-nitroazetidine. Surprisingly, no Br dissociation is observed despite its high electron affinity. We assign this behavior to the "inaccessibility" of sigma virtual states for electrons in the solvent, which can be of a general nature.

• Klíčová slova
• catalytic electron, electron attachment, low‐energy electrons, radiosensitizer, state selective,
• Publikační typ
• časopisecké články MeSH

Details of electron-induced chemistry of methyl methacrylate (MMA) upon complexation are revealed by combining gas-phase 2D electron energy loss spectroscopy with electron attachment spectroscopy of isolated MMA and its clusters. We show that even though isolated MMA does not form stable parent anions, it efficiently thermalizes the incident electrons via intramolecular vibrational redistribution, leading to autodetachment of slow electrons. This autodetachment channel is reduced in clusters due to intermolecular energy transfer and stabilization of parent molecular anions. Bond breaking via dissociative electron attachment leads to an extensive range of anion products. The dominant OCH3- channel is accessible via core-excited resonances with threshold above 5 eV, despite the estimated thermodynamic threshold below 3 eV. This changes in clusters, where MnOCH3- anions are observed in a lower-lying resonance due to neutral dissociation of the 1(n, π*) state and electron self-scavenging. The present findings have implications for electron-induced chemistry in lithography with poly(methyl methacrylate).

• Publikační typ
• časopisecké články MeSH

Metronidazole belongs to the class of nitroimidazole molecules and has been considered as a potential radiosensitizer for radiation therapy. During the irradiation of biological tissue, secondary electrons are released that may interact with molecules of the surrounding environment. Here, we present a study of electron attachment to metronidazole that aims to investigate possible reactions in the molecule upon anion formation. Another purpose is to elucidate the effect of microhydration on electron-induced reactions in metronidazole. We use two crossed electron/molecular beam devices with the mass-spectrometric analysis of formed anions. The experiments are supported by quantum chemical calculations on thermodynamic properties such as electron affinities and thresholds of anion formation. For the single molecule, as well as the microhydrated condition, we observe the parent radical anion as the most abundant product anion upon electron attachment. A variety of fragment anions are observed for the isolated molecule, with NO2- as the most abundant fragment species. NO2- and all other fragment anions except weakly abundant OH- are quenched upon microhydration. The relative abundances suggest the parent radical anion of metronidazole as a biologically relevant species after the physicochemical stage of radiation damage. We also conclude from the present results that metronidazole is highly susceptible to low-energy electrons.

• Klíčová slova
• clusters, electron attachment, hydration, low-energy electron, metronidazole, radiosensitizer, reduction,
• Publikační typ
• časopisecké články MeSH

We report experimental results of low-energy electron interactions with.

• Klíčová slova
• dissociative electron attachment, low-energy electrons, pyrimidine, radiosensitizer,
• MeSH
• chemické modely MeSH
• dlaždicobuněčné karcinomy hlavy a krku chemie   farmakoterapie   radioterapie   MeSH
• dusíkaté sloučeniny chemie   farmakologie   MeSH
• elektrony * MeSH
• ionizující záření MeSH
• lidé MeSH
• molekulární modely MeSH
• nádorové buněčné linie MeSH
• nádory hypofaryngu chemie   farmakoterapie   radioterapie   MeSH
• pyrimidiny chemie   farmakologie   MeSH
• radiosenzibilizující látky chemie   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 2,4-dichloropyrimidine MeSH Prohlížeč
• dusíkaté sloučeniny MeSH
• pyrimidiny MeSH
• radiosenzibilizující látky MeSH

We study the reactivity of misonidazole with low-energy electrons in a water environment combining experiment and theoretical modelling. The environment is modelled by sequential hydration of misonidazole clusters in vacuum. The well-defined experimental conditions enable computational modeling of the observed reactions. While the NO 2 - dissociative electron attachment channel is suppressed, as also observed previously for other molecules, the OH - channel remains open. Such behavior is enabled by the high hydration energy of OH - and ring formation in the neutral radical co-fragment. These observations help to understand the mechanism of bio-reductive drug action. Electron-induced formation of covalent bonds is then important not only for biological processes but may find applications also in technology.

• Klíčová slova
• bond formation, clusters, electron attachment, low-energy electron, misonidazole,
• MeSH
• elektrony * MeSH
• misonidazol chemie   MeSH
• molekulární modely MeSH
• molekulární struktura MeSH
• rozpouštědla MeSH
• spektrální analýza MeSH
• teoretické modely MeSH
• voda MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• misonidazol MeSH
• rozpouštědla MeSH
• voda MeSH