Dissociative Electron Attachment Dynamics of a Promising Cancer Drug Indicates Its Radiosensitizing Potential

Abstract

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 intersystem crossing 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.