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Dissociative Electron Attachment to 8-(Trifluoromethyl)thioadenine: A Potential Radiosensitizer
Adrian Szczyrba1, Magdalena Datta1,2, Samanta Makurat1
1Laboratory of Biological Sensitizers, Department of Physical Chemistry, Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, Gdańsk80-308, Poland.
Abstract:
The development of new biological radiosensitizers has primarily focused on halogenated uracil-based derivatives such as 5-bromo-2'-deoxyuridine, and more recently, 5-iodo-4-thio-2'-deoxyuridine or 5-thiocyanato-2'-deoxyuridine. However, further modifications of the uracil/uridine ring are limited due to challenges related to synthesis and stability. In this study, we investigate dissociative electron attachment (DEA) to 8-(trifluoromethyl)thioadenine (ASCF3), proposing a new potential purine-based radiosensitizer for cancer cells. This is explored using a crossed electron-molecule beam (CEMB) experiment and stationary radiolysis in an aqueous environment. To support our findings, we combined experimental results with theoretical calculations employing DFT methods to analyze the energy threshold and DEA profiles. The most abundant anion observed in the CEMB experiments corresponds to [ASCF3-CF3]-, whereas the radiolytic study reveals that the novel derivative undergoes a single decomposition channel in aqueous solution, yielding a cyclic [ASCF3-HF] species. These findings highlight that disregarding the influence of water in cellular processes may lead to erroneous mechanistic conclusions.
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