5-selenocyanatouracil: a potential hypoxic radiosensitizer. Electron attachment induced formation of selenium centered radical

Marta Sosnowska , Samanta Makurat , Magdalena Zdrowowicz , Janusz Rak

Abstract

The propensity of 5-selenocyanatouracil (SeCNU) to decomposition induced by attachment of electron was scrutinized with the G3B3 composite quantum-chemical method and radiolytic studies. Favorable thermodynamic (Gibbs free reaction energy of -13.65 kcal/mol) and kinetic (Gibbs free activation energy of 1.21 kcal/mol) characteristics revealed by the G3B3 free energy profile suggest SeCNU to be sensitive to electron attachment. The title compound was synthesized in the reaction between uracil and selenocyanogen chloride in acetic acid. Then, an aqueous and deoxygenated solution of the HPLC purified compound containing tert-butanol as a hydroxyl radical scavenger was irradiated with X-rays. SeCNU radio-degradation results in two major products: the U-Se-Se-U dimer and the adduct of the (center dot)OtBu radical to the U-Se-center dot radical, U-Se-OtBu. The effects of radiolysis as well as the results of G3B3 calculations point to U-Se-center dot as the primary product of dissociative electron attachment to SeCNU. The MTT test shows that SeCNU is nontoxic in vitro in concentrations equal to or lower than 10(-6) M. Ionizing radiation will probably induce cytotoxic intra- and interstrand DNA cross-links as well as protein-DNA cross-links in the genomic DNA labeled with SeCNU.
Author Marta Sosnowska PSB
Marta Sosnowska,,
- Laboratory of Biological Sensitizers
, Samanta Makurat PSB
Samanta Makurat,,
- Laboratory of Biological Sensitizers
, Magdalena Zdrowowicz PSB
Magdalena Zdrowowicz,,
- Laboratory of Biological Sensitizers
, Janusz Rak PSB
Janusz Rak,,
- Laboratory of Biological Sensitizers
Other language title versions
Journal seriesJournal of Physical Chemistry B, ISSN 1520-6106
Issue year2017
Vol121
No25
Pages6139-6147
Publication size in sheets0.5
DOIDOI:10.1021/acs.jpcb.7b03633
URL http://pubs.acs.org/doi/ipdf/10.1021/acs.jpcb.7b03633
Languageen angielski
Score (nominal)30
ScoreMinisterial score = 30.0, 20-12-2017, ArticleFromJournal
Ministerial score (2013-2016) = 30.0, 20-12-2017, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 3.177 (2) - 2016=3.177 (5)
Citation count*0
Cite
Share Share

Get link to the record
msginfo.png


* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
Back