5-Selenocyanato and 5-trifluoromethanesulfonyl derivatives of 2'-deoxyuridine: synthesis, radiation and computational chemistry as well as cytotoxicity

Samanta Makurat , Magdalena Zdrowowicz , Lidia Chomicz-Mańka , Witold Kozak , Illia Serdiuk , Paweł Wityk , Alicja Kawecka , Marta Sosnowska , Janusz Rak

Abstract

5-Selenocyanato-2'-deoxyuridine(SeCNdU)and 5-trifluoromethanesulfonyl-2'-deoxyuridine (OTfdU)have been synthesized and their structures have been confirmed with NMR and MS methods. Both compounds undergo dissociative electron attachment (DEA) when irradiated with X-rays in an aqueous solution containing a hydroxyl radical scavenger. The DEA yield of SeCNdU significantly exceeds that of 5-bromo-2'-deoxyuridine (BrdU), remaining in good agreement with the computationally revealed profile of electron-induced degradation. The radiolysis products indicate, in line with theoretical predictions, Se–CN bond dissociation as the main reaction channel. On the other hand, the DEA yield for OTfdU is slightly lower than the degradation yield measured for BrdU, despite the fact that the calculated driving force for the electron-induced OTfdU dissociation substantially overpasses the thermodynamic stimulus for BrdU degradation. Moreover, the calculated DEA profile suggests that the electron attachment induced formation of 5-hydroxy-2'-deoxyuridine (OHdU) from OTfdU, while 2'-deoxyuridine (dU) is mainly observed experimentally. We explained this discrepancy in terms of the increased acidity of OTfdU resulting in efficient deprotonation of the N3 atom, which brings about the domination of the OTfdU(N3–H)-anion in the equilibrium mixture. As a consequence, electron addition chiefly leads to the radical dianion, OTfdU(N3–H).2-, which easily protonates at the C5 site. As a result, the C5–O rather than O–S bond undergoes dissociation, leading to dU, observed experimentally. A negligible cytotoxicity of the studied compounds toward the MCF-7 cell line at the concentrations used for cell labelling calls for further studies aiming at the clinical use of the proposed derivatives.
Author Samanta Makurat (FCh / DPCh / LBS)
Samanta Makurat,,
- Laboratory of Biological Sensitizers
, Magdalena Zdrowowicz (FCh / DPCh / LBS)
Magdalena Zdrowowicz,,
- Laboratory of Biological Sensitizers
, Lidia Chomicz-Mańka (FCh / DPCh / LBS)
Lidia Chomicz-Mańka,,
- Laboratory of Biological Sensitizers
, Witold Kozak (FCh / DPCh / LBS)
Witold Kozak,,
- Laboratory of Biological Sensitizers
, Illia Serdiuk (FMPI / IEP)
Illia Serdiuk,,
- Institute of Experimental Physics
, Paweł Wityk (FCh / DPCh / LBS)
Paweł Wityk,,
- Laboratory of Biological Sensitizers
, Alicja Kawecka (FCh / DPCh / LLR)
Alicja Kawecka,,
- Laboratory of Luminescence Research
, Marta Sosnowska (FCh / DPCh / LBS)
Marta Sosnowska,,
- Laboratory of Biological Sensitizers
, Janusz Rak (FCh / DPCh / LBS)
Janusz Rak,,
- Laboratory of Biological Sensitizers
Journal seriesRSC Advances, ISSN 2046-2069, (A 30 pkt)
Issue year2018
Vol8
No38
Pages21378-21388
Publication size in sheets0.5
DOIDOI:10.1039/c8ra03172j
URL http://pubs.rsc.org/en/content/articlehtml/2018/ra/c8ra03172j
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa - Użycie Niekomercyjne (CC-BY-NC); with publication
Score (nominal)35
ScoreMinisterial score = 30.0, 23-07-2018, ArticleFromJournal
Ministerial score (2013-2016) = 35.0, 23-07-2018, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 3.108 (2) - 2016=3.257 (5)
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