Dissociative Electron Attachment in 1,3-Dimethyl-5-Thiocyanatouracil at Different Hydration Conditions

Abstract 5-Thiocyanato-2′-deoxyuridine has emerged as a promising radiosensitizer for cancer radiotherapy. Upon X-ray irradiation, hydrated electrons generated in the tumor microenvironment can interact with this molecule, forming reactive transient species capable of inducing damage to DNA, the primary target of radiotherapy. In this work, we investigate dissociative electron attachment (DEA) to 1,3-dimethyl-5-thiocyanatouracil, a doubly methylated analogue of 5-thiocyanato-2′-deoxyuridine, in both the gas phase and microhydrated environments. Gas-phase measurements were performed using a crossed electron–molecular beam apparatus coupled with mass spectrometry, while microhydrated clusters were examined using a CLUster-Beam setup, enabling direct assessment of hydration effects on DEA. The experimental results are supported by quantum chemical calculations, providing insight into thermodynamic and kinetic parameters, including electron affinities, reaction thresholds, and activation barriers. In both environments, the parent anion and the CN– fragment dominate the product distribution, accompanied by minor channels such as SCN– formation. Microhydration leads to a moderate suppression of the S–CN bond cleavage pathway but does not inhibit the reaction. Overall, these findings demonstrate that microhydration modulates, yet preserves, DEA activity in this class of radiosensitizers, supporting their potential effectiveness under biologically relevant conditions.