Nitro rotation tuned dissociative electron attachment upon targeted radiosensitizer 4-substituted Z bases

In this work, a set of new potential radiation sensitizers (4-substituted Z-bases: 4XZ, X = F, Cl, Br, and I) are designed based on the artificial 6-amino-5-nitro-3-(1'-β-D-2'-deoxyribofuranosyl)-2(1H)-pyridone (Z), which can selectively bind to breast cancer cells. The calculated electron affinities in water solution show that the halogenated Z-bases are efficient electron acceptors which possess significant electron-withdrawing characters following the order of 4XZ > Z ≫ U. To ensure the effective electron attachment induced dissociation, we constructed the energy profiles related to the X-C bond cleavage of neutral and anionic bases. The results show that the X-C bond becomes relatively weak after the electron attachment. In particular, the electron induced dehalogenations of (4BrZ)^- and (4IZ)^- are low-barrier and exothermic, which support a high radiosensitivity. Furthermore, we characterized the vibrational excitation effect on the dissociative electron attachment, which demonstrates that the charge distribution can be regulated by the rotation-induced structural distortion accompanied by the electron localization on the nitro group. Also examined is the influence of base pairing on the dehalogenation, which is not only conducive to the electron-driven dissociation but is also beneficial to the stabilization of related products. The current study suggests 4BrZ and 4IZ can be regarded as potential targeted radiosensitizers with possible applications in reducing the side effects in radiotherapy.