2-Bromo-1-(3,3-dinitroazetidin-1-yl)ethan-1-one (RRx-001) is a hypoxic cell chemotherapeutics with already demonstrated synergism in combined chemo-radiation therapy. The interaction of the compound with secondary low-energy electrons formed in large amounts during the physico-chemical phase of the irradiation may lead to these synergistic effects. The present study focuses on the first step of RRx-001 interaction with low-energy electrons in which a transient anion is formed and fragmented. Combination of two experiments allows us to disentangle the decay of the RRx-001 anion on different timescales. Sole presence of the electron initiates rapid dissociation of NO2 and HNO2 neutrals while NO2 - and Br- anions are produced both directly and via intermediate complexes. Based on our quantum chemical calculations, we propose that bidirectional state switching between π*(NO2) and σ*(C-Br) states explains the experimental spectra. The fast dynamics monitored will impact the condensed phase chemistry of the anion as well.

Center for Biomolecular Sciences Innsbruck Universität Innsbruck Technikerstrasse 25 A 6020 Innsbruck Austria

Department of Nuclear Chemistry Faculty of Nuclear Sciences and Physical Engineering Czech Technical University Prague Břehová 78 7 115 19 Prague Czech Republic

Institut für Ionenphysik und Angewandte Physik Universität Innsbruck Technikerstrasse 25 A 6020 Innsbruck Austria

J Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences v v i Dolejškova 3 18223 Prague Czech Republic

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Low-Energy Electron-Induced Dissociation of the Radiosensitizing Agent Sanazole

Nitro-Group π System Drives the Interaction of RRx-001 with Electrons in Solution