Abstract
Misonidazole (MISO) was considered as radiosensitizer for the treatment of hypoxic tumors. A prerequisite for entering a hypoxic cell is reduction of the drug, which may occur in the early physical-chemical stage of radiation damage. Here we study electron attachment to MISO and find that it very effectively captures low energy electrons to form the non-decomposed molecular anion. This associative attachment (AA) process is exclusively operative within a very narrow resonance right at threshold (zero electron energy). In addition, a variety of negatively charged fragments are observed in the electron energy range 0–10 eV arising from dissociative electron attachment (DEA) processes. The observed DEA reactions include single bond cleavages (formation of NO2−), multiple bond cleavages (excision of CN−) as well as complex reactions associated with rearrangement in the transitory anion and formation of new molecules (loss of a neutral H2O unit). While any of these AA and DEA processes represent a reduction of the MISO molecule, the radicals formed in the course of the DEA reactions may play an important role in the action of MISO as radiosensitizer inside the hypoxic cell. The present results may thus reveal details of the molecular description of the action of MISO in hypoxic cells.
Highlights
A variety of nitroimidazole derivatives have been under investigation for their potential use in cancer therapy [1,2]
The radicals generated in the course of the dissociative electron attachment (DEA) reactions are presumably relevant in the action of MISO as radiosensitizer inside the below, MISO is very effectively reduced by capturing low energy electrons
The radicals generated in the course of the DEA reactions are presumably relevant in the action of MISO as radiosensitizer inside the hypoxic cell
Summary
A variety of nitroimidazole derivatives have been under investigation for their potential use in cancer therapy [1,2]. We study free electron attachment to the gas phase nitroimidazolic derivative misonidazole (MISO) (C7 H11 N3 O4 ; see Figure 1a for the molecular structure) which was clinically tested in trails as radiosensitizer for the treatment of hypoxic tumors [2]. Such tumors are characterized by a significant low oxygen state compared to the normal cell tissue. Reduction of MISO is performed with zinc, ammonium, or by radiolysis by high-energy quanta (particles or photons in the MeV range)
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