Abstract
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.
Highlights
Radiotherapy is one of the most common modalities in anticancer treatment
We report for the first time on the physicochemical characteristics of uracil-5-yl O-sulfamate (SU, NH2SO3C4H4N2O2; molecular mass 207 g·mol−1), a potential radiosensitizer
A favorable dissociative electron attachment (DEA) profile calculated for OTfdU was confirmed by the extent of its radiolytic decomposition in water solution, which was similar to that measured for BrdU under the same experimental conditions
Summary
Radiotherapy is one of the most common modalities in anticancer treatment. around 80% of cancerous patients are exposed to ionizing radiation (IR) at certain stages of their therapy.[1]. 2.11 2.40 nucleobases, nucleotides, and DNA almost at a diffusion controlled rate.[12] no strand breaks are produced as a result of electron attachment to the native DNA, which was proved experimentally[13] and justified theoretically.[14] Only specific chemical modifications to the DNA monomeric units make them prone to dissociative electron attachment (DEA).[15] The mechanism that utilizes electrons unreactive toward native DNA and is operative under hypoxia when the damaging properties of hydroxyl radical are significantly impaired prompted us to propose several new uridine radiosensitizers To this end, 5-selenocyanato-2′-deoxyuridine (SeCNdU),16 5trifluoromethanesulfonyl-2′-deoxyuridine (OTfdU),16 5-iodo4-thio-2′-deoxyuridine (ISdU),[17] or 5-thiocyanato-2′-deoxyuridine (SCNdU)[18] can be mentioned as representative examples. The outcome of radiolysis of water solutions containing the studied compound has been interpreted in terms of measured pKa and the DEA profile calculated at the G2MP2 level
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