Uracil-5-yl O-Sulfamate: An Illusive Radiosensitizer. Pitfalls in Modeling the Radiosensitizing Derivatives of Nucleobases.

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.