Dynamics of Ring-Cleavage Reactions in Temozolomide Induced by Low-Energy Electron Attachment

Abstract

We have used a crossed electron molecular beam setup to investigate the behavior of the anticancer drug temozolomide (TMZ) upon the attachment of low-energy electrons (0–14 eV) in the gas phase. Upon a single electron attachment, eight anionic fragments are observed, the most intense being an anion with mass of 109 u at a resonance energy of 0 eV. Quantum chemical calculations suggest that this ion is generated after the tetrazine ring opens along a N–N bond and its fragments leave the molecule, forming an imidazole-carboxamide species. This ion represents the most abundant fragment, with further fragments following from its dissociation. The tetrazine ring cleavage reaction forming N2 is thus the driving force of TMZ reactivity upon electron attachment.

Electron-Induced Decomposition of 5-Bromo-4-thiouracil and 5-Bromo-4-thio-2′-deoxyuridine: The Effect of the Deoxyribose Moiety on Dissociative Electron Attachment

“…As the radiation passes through the medium, a large portion of the deposited energy is channeled into the generation of low-energy electrons (LEEs) with kinetic energies less than a few hundred eV and an energy distribution maximum of approximately 9-10 eV [5]. When DNA is exposed to so-called ballistic electrons, the latter are known to induce DNA damage such as single-and double-strand breaks, base release, and sugar modifications upon dissociative electron attachment (DEA) [6][7][8][9]. However, electrons are just not detrimental to hydrated DNA with respect to strand breaks [10,11].…”

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

“…In recent years, investigations with isolated or microhydrated DNA constituents in the gas phase substantially contributed to the understanding of the dynamics of electron attachment to biomolecular systems. − This knowledge is also essential in the search for new molecules, which should enhance the effects of ionizing radiation in tumor cells. − Such so-called radiosensitizers may be designed so that they are particularly prone to low-energy electron attachment. , DEA could be then a mechanism that is exploited for the generation of species (like free radicals) damaging the DNA in tumor cells. − To study the basic electron attachment properties of potential radiosensitizers, crossed electron-molecule beam (CEMB) experiments were carried out. − There was early interest in DEA to halogenated uracils . The incorporation of these modified uracils into native DNA should enhance radiation-induced cell killing due to their strong electrophilic properties and low cytotoxicity toward cancer and normal cells …”