Dissociative Electron Attachment to 5‑Iodo-4-thio-2′-deoxyuridine: A Potential Radiosensitizer of Hypoxic Cells

In the search for
effective radiosensitizers for tumor cells, halogenated
uracils have attracted more attention due to their large cross section
for dissociation upon the attachment of low-energy electrons. In this
study, we investigated dissociative electron attachment (DEA) to 5-iodo-4-thio-2′-deoxyuridine,
a potential radiosensitizer using a crossed electron-molecule beam
experiment coupled with quadrupole mass spectrometry. The experimental
results were supported by calculations on the threshold energies of
formed anions and transition state calculations. We show that low-energy
electrons with kinetic energies near 0 eV may effectively decompose
the molecule upon DEA. The by far most abundant anion observed corresponds
to the iodine anion (I–). Due to the associated
bond cleavage, a radical site is formed at the C5 position, which
may initiate strand break formation if the molecule is incorporated
into a DNA strand. Our results reflect the conclusion from previous
radiolysis studies with the title compound, suggesting its potential
as a radiosensitizer.