Journal article
The Site of Azido Substitution in a Pyrimidine Nucleobase Dictates the Type of Nitrogen-Centered Radical Formed after Dissociative Electron Attachment
The journal of physical chemistry. B, Vol.129(32), pp.8115-8126
08/04/2025
DOI: 10.1021/acs.jpcb.5c02751
PMCID: PMC12359106
PMID: 40758826
Appears in UI Libraries Support Open Access
Abstract
Azido(N3)-nucleosides are known for their antiviral and anticancer properties. Recently, N3-nucleosides have attracted attention for augmenting radiation damage in tumor cells via dissociative electron attachment (DEA) reactions mediated by the simplest and the most potent reducing species (the electron). To investigate the effect of N3 group substitution at specific sites of the pyrimidine base-ring (C4, C5, and C6) on the DEA reaction, we employed both commercially available and in-house-synthesized N3-nucleosides. We conducted a comprehensive study combining electron paramagnetic resonance (EPR) spectroscopy at a low temperature, picosecond pulse radiolysis in an aqueous solution under ambient conditions, and DFT calculations. For N3 substitution at C4, EPR studies and DFT calculations established a stable azide anion radical (R–N3•–) formation, after the addition of radiation-produced electrons. For N3 substitution at C5, the DEA leads to a π-type aminyl radical (R–NH•) formation. For N3 substitution at C6, a conjugated iminyl σ-radical (R═N•) is formed via DEA. R═N• is in equilibrium with R–NH•. Thus, this work reports a significant finding: the stabilization and reactivity of each type of nitrogen-centered radical (RN3•–, RNH•, R═N•) are determined by the position of N3 substitution on the pyrimidine base-ring.
Details
- Title: Subtitle
- The Site of Azido Substitution in a Pyrimidine Nucleobase Dictates the Type of Nitrogen-Centered Radical Formed after Dissociative Electron Attachment
- Creators
- Daniel Adjei - Institut de ChimieMaria de Cabrera - Florida International UniversityYahaira Reyes - Florida International UniversityAlexandru Barbolovici - Association of Research LibrariesMoaadh Alahmadi - Association of Research LibrariesSamuel Ward - Department of Chemistry, 146 Library DriveMarie-Claude Menet - IUT d’OrsayPhilippe Mejanelle - IUT d’OrsayAnil Kumar - Association of Research LibrariesMichael D. Sevilla - Association of Research LibrariesStanislaw F. Wnuk - Florida International UniversityMehran Mostafavi - Laboratoire de Chimie PhysiqueAmitava Adhikary - University of Iowa, Radiation Oncology
- Resource Type
- Journal article
- Publication Details
- The journal of physical chemistry. B, Vol.129(32), pp.8115-8126
- DOI
- 10.1021/acs.jpcb.5c02751
- PMID
- 40758826
- PMCID
- PMC12359106
- NLM abbreviation
- J Phys Chem B
- ISSN
- 1520-6106
- eISSN
- 1520-5207
- Publisher
- American Chemical Society
- Number of pages
- 12
- Copyright
- Copyright © 2025 The Authors
- Language
- English
- Date published
- 08/04/2025
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984963944302771
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