5-trifluoromethanesulfonyl-uracil (OTfU), a recently proposed radiosensitizer, is decomposed in the gas-phase by attachment of low-energy electrons. OTfU is a derivative of uracil with a triflate (OTf) group at the C 5-position, which substantially increases its ability to undergo effective electron-induced dissociation. We report a rich assortment of fragments formed upon dissociative electron attachment (DEA), mostly by simple bond cleavages (e.g., dehydrogenation or formation of OTf −). The most favorable DEA channel corresponds to the formation of the triflate anion alongside with the reactive uracil-5-yl radical through the cleavage of the O-C 5 bond, particularly at about 0 eV. Unlike for halouracils, the parent anion was not detected in our experiments. The experimental findings are accounted by a comprehensive theoretical study carried out at the M06-2X/aug-cc-pVTZ level. The latter comprises the thermodynamic thresholds for the formation of the observed anions calculated under the experimental conditions (383.15 K and 3 × 10 −11 atm). The energy-resolved ion yield of the dehydrogenated parent anion, (OTfU-H) − , is discussed in terms of vibrational Feshbach resonances arising from the coupling between the dipole bound state and vibrational levels of the transient negative ion. We also report the mass spectrum of the cations obtained through ionization of OTfU by electrons with a kinetic energy of 70 eV. The current study endorses OTfU as a potential radiosensitizer agent with possible applications in radio-chemotherapy.

Tirapazamine (TPZ) has been tested in clinical trials on radio‐chemotherapy due to its potential highly selective toxicity towards hypoxic tumor cells. It was suggested that either the hydroxyl radical or benzotriazinyl radical may form as bioactive radical after the initial reduction of TPZ in solution. In the present work, we studied low‐energy electron attachment to TPZ in the gas phase and investigated the decomposition of the formed TPZ− anion by mass spectrometry. We observed the formation of the (TPZ–OH)− anion accompanied by the dissociation of the hydroxyl radical as by far the most abundant reaction pathway upon attachment of a low‐energy electron. Quantum chemical calculations suggest that NH2 pyramidalization is the key reaction coordinate for the reaction dynamics upon electron attachment. We propose an OH roaming mechanism for other reaction channels observed, in competition with the OH dissociation.

Efficient radiotherapy requires the concomitant use of ionizing radiation (IR) and a radiosensitizer. In the present work uracil-5-yl O -sulfamate (SU) is tested against its radiosensitizing potential. The compound possesses appropriate dissociative electron attachment (DEA) characteristics calculated at the M06-2X/6-31++G(d,p) level. Crossed electron–molecular beam experiments in the gas phase demonstrate that SU undergoes efficient DEA processes, and the single C–O or S–O bond dissociations account for the majority of fragments induced by electron attachment. Most DEAs proceed already for electrons with kinetic energies of ∼0 eV, which is supported by the exothermic thresholds calculated at the M06-2X/aug-cc-pVTZ level. However, in water solution under reductive conditions and physiological pH, SU does not undergo radiolysis, which demonstrates the crucial influence of aqueous environment on the radiosensitizing properties of modified nucleosides.

We investigate dissociative electron attachment to 5-fluorouracil (5-FU) employing a crossed electron-molecular beam experiment and quantum chemical calculations. Upon the formation of the 5-FU− anion, 12 different fragmentation products are observed, the most probable dissociation channel being H loss. The parent anion, 5-FU−, is not stable on the experimental timescale (~140 µs), most probably due to the low electron affinity of FU; simple HF loss and F− formation are seen only with a rather weak abundance. The initial dynamics upon electron attachment seems to be governed by hydrogen atom pre-dissociation followed by either its full dissociation or roaming in the vicinity of the molecule, recombining eventually into the HF molecule. When the HF molecule is formed, the released energy might be used for various ring cleavage reactions. Our results show that higher yields of the fluorine anion are most probably prevented through both faster dissociation of an H atom and recombination of F− with a proton to form HF. Resonance calculations indicate that F− is formed upon shape as well as core-excited resonances.

We investigate dissociative electron attachment to tirapazamine through a crossed electron–molecule beam experiment and quantum chemical calculations. After the electron is attached and the resulting anion reaches the first excited state, D1, we suggest a fast transition into the ground electronic state through a conical intersection with a distorted triazine ring that almost coincides with the minimum in the D1 state. Through analysis of all observed dissociative pathways producing heavier ions (90–161 u), we consider the predissociation of an OH radical with possible roaming mechanism, as introduced in our recent letter [Angew Chem Int. Ed., 59, 17177 (2020)], to be the common first step. This destabilizes the triazine ring and leads to dissociation of highly stable nitrogen-containing species. The benzene ring is not altered during the process. Dissociation of small anionic fragments (NO2−, CN2−, CN−, NH2−, O−) cannot be conclusively linked to the OH predissociation mechanism; however, they again do not require dissociation of the benzene ring.