Observation of Transient Anions That Do Not Decay through Dissociative Electron Attachment: New Pathways for Radiosensitization

Abstract

Low-energy electrons (LEEs) can very efficiently induce bond breaking via dissociative electron attachment (DEA). While DEA is ubiquitous, the importance of other reactions initiated by LEEs remains much more elusive. Here, we looked into this question by measuring highly accurate total cross sections for electron scattering from 1-methyl-5-nitroimidazole (1M5NI), a model radiosensitizer. The small uncertainty and high energy resolution allow us to identify many resonant features related to the formation of transient anions. In addition to novel insights about DEA reactions through the lower-lying resonances, our key finding is that the higher-lying resonances do not undergo DEA, implying alternative decay channels with significant cross sections. In particular, dissociation into two neutral fragments is probably involved in the case of 1M5NI. This finding has direct implications for the understanding of LEE-induced chemistry, particularly in the fundamental processes underlying the radiosensitization activity.

Interaction of low-energy electrons with radiosensitizers

“…In the study of a model compound 1-methyl-5-nitroimidazole, it was suggested that dissociation into two neutral fragments may occur at these energies, pointing out the importance of the studies of neutral dissociation products upon electron attachment. 80 The total scattering cross section at low energies was complemented by differential and DEA as well as ionization cross sections in the follow-up publication. 196 We would like to add that in complex environments the core excited resonances may play an important role irrespective of the dissociation as they can act as doorways for electron transfer (Fig.…”

“…However, the DEA to unbound molecules in the cellular medium can produce reactive radicals leading to cell stress and death. 80,81 An interesting suggestion is also that the presence of heavy metal atoms, such as Pt can locally enhance the production of reactive LEEs. 82…”

DNA Protection against Damages Induced by Low-Energy Electrons: Absolute Cross Sections for Arginine–DNA Complexes

“…The interaction of 5 and 10 eV electrons with DNA principally results in the formation of core-excited TAs. , These TAs are formed by temporary LEE capture into the potential well of an electronically excited state of a base. ,− They can decay by dissociative electron attachment (DEA), thereby leading to BD, or the additional electron transfers to another base or the phosphate group where a lesion can be produced via DEA. When the initial base is left in a neutral dissociative excited state, a double lesion can be formed. , The possible combinations of BDs and transfer sites lead to the damages listed in Table . The magnitude of these damages relies essentially on the electron attachment probability to the bases, electron transfer rate to PO 4 – , and lifetime of TAs formed on the base and phosphate subunits. ,− In both complexes, these parameters should be affected by “scavenging” and the different counterion at the O – terminal of the phosphate .…”

“…When the initial base is left in a neutral dissociative excited state, a double lesion can be formed. 80,81 The possible combinations of BDs and transfer sites lead to the damages listed in Table 1. 80 The magnitude of these damages relies essentially on the electron attachment probability to the bases, electron transfer rate to PO 4 − , and lifetime of TAs formed on the base and phosphate subunits.…”

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 …”