Electron-Induced Dissociation of the Potential Radiosensitizer 5-Selenocyanato-2′-deoxyuridine

Abstract

5-Selenocyanato-2′-deoxyuridine (SeCNdU) is a recently proposed radiosensitizer based on 2′-deoxyuridine (dU) with the electron-affinic selenocyanato (−SeCN) side group attached at the C5 position of uracil. Since electron interaction processes may be an important source of DNA damage by ionizing radiation, we have studied low-energy dissociative electron attachment to SeCNdU in the gas phase. Negative ion formation has been obtained by means of mass spectrometry, where a rich fragmentation pattern is observed even at ∼0 eV. The reaction pathways exhibiting the highest ion yields are C 4 N 2 O 2 H 2 Se •− and CN − , both involving a cleavage of the Se−CN bond. The heaviest fragment anion observed is C 9 N 2 O 5 H 10 Se •− , where besides the charged species, the hydrogen and cyano radicals are also formed. Further decomposition channels also yield the highly reactive hydroxyl radical, which possesses a high DNA damage potential. All observed channels have experimentally determined onsets at 0 eV, which are supported by calculations performed at the M06-2X/aug-cc-pVTZ level. The calculations comprise the thermochemical thresholds at standard and experimental (428.15 K, 3 × 10 −11 atm) conditions together with the adiabatic electron affinities. The present study shows that low-energy electrons very effectively decompose SeCNdU upon attachment of thermal electrons, producing a large variety of charged fragments and radicals.

Reactions in the Radiosensitizer Misonidazole Induced by Low-Energy (0–10 eV) Electrons

“…Previous studies showed that DEA can be an effective process in breaking bonds and hence generates radicals at electron energies considerably below typical bond dissociation energies [10,11,12,13,14]. Such behavior was also observed in DEA studies with radiosensitizers like modified nucleobases [5,6,17,18,19,20]. By modification of the native nucleobase by highly electron affinic side groups, an increase of the DEA cross section can be achieved.…”

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

“…The decomposition of a potential radiosensitizer by LEEs can be studied in the gas phase using a crossed electron–molecular beam technique, which utilizes mass spectrometry for the analysis of fragment anions formed as a result of DEA. 25 , 26 …”

Damage Induced to DNA and Its Constituents by 0–3 eV UV Photoelectrons†

“…Cell radiosensitization by such halogen derivatives incorporated in the DNA has been demonstrated (100), and related to DEA (101), thus indicating that this process triggered by near 0 eV electron attachment to a modified base (102) occurs in the nucleus. New molecules (103–107) that may act like halouridines, but with better characteristics for therapeutic cancer treatment are presently being developed and investigated.…”