Search
5-Thiocyanato-2′-deoxyuridine as a possible radiosensitizer: electron-induced formation of uracil-C5-thiyl radical and its dimerization
Abstract
In this work, we have synthesized 5-thiocyanato-2′-deoxyuridine (SCNdU) along with the C6-deuterated nucleobase 5-thiocyanatouracil (6-D-SCNU) and studied their reactions with radiation-produced electrons. ESR spectra in γ-irradiated nitrogen-saturated frozen homogeneous solutions (7.5 M LiCl in H2O or D2O) of these compounds show that electron-induced S–CN bond cleavage occurs to form a thiyl radical (dU-5-S˙ or 6-D-U-5-S˙) and CN−via the initial π-anion radical (SCNdU˙−) intermediate in which the excess electron is on the uracil base. HPLC and LC-MS/MS studies of γ-irradiated N2-saturated aqueous solutions of SCNdU in the presence of sodium formate as a OH-radical scavenger at ambient temperature show the formation of the dU-5S-5S-dU dimer in preference to dU by about 10 to 1 ratio. This shows that both possible routes of electron-induced bond cleavage (dUC5–SCN and S–CN) in SCNdU˙− and dU-5-S˙ formation are preferred for the production of the σ-type uracilyl radical (dU˙) by 10 fold. DFT/M06-2x/6-31++G(d,p) calculations employing the polarizable continuum model (PCM) for aqueous solutions show that dU-5-S˙ and CN− formation was thermodynamically favored by over 15 kcal mol−1 (ΔG) compared to dU˙ and SCN− production. The activation barriers for C5–S and S–CN bond cleavage in SCNdU˙− amount to 8.7 and 4.0 kcal mol−1, respectively, favoring dU-5-S˙ and CN− formation. These results support the experimental observation of S–CN bond cleavage by electron addition to SCNdU that results in the formation of dU-5-S˙ and the subsequent dU-5S-5S-dU dimer. This establishes SCNdU as a potential radiosensitizer that could cause intra- and inter-strand crosslinking as well as DNA–protein crosslinking via S–S dimer formation.
Citations
-
2 9
CrossRef
-
0
Web of Science
-
2 4
Scopus
Authors (9)
-
Magdalena Zdrowowicz
- Uniwersytet Gdański/Wydział Chemii Chemii Fizycznej
-
Lidia Chomicz
- Uniwersytet Gdański/Wydział Chemii Chemii Fizycznej
-
Michał Żyndul
- Uniwersytet Gdański/Wydział Chemii Chemii Fizycznej
-
-
Janusz Rak Prof.
- Uniwersytet Gdański/Wydział Chemii Chemii Fizycznej
-
Tyler Wiegand
- Oakland Univeristy
-
Cameron Hanson
- Oakland Univeristy
-
Amitava Adhikary
- Oakland Univeristy
-
Michael Sevilla
- Oakland Univeristy
Cite as
Full text
full text is not available in portal
Keywords
Details
- Category:
- Articles
- Type:
- artykuł w czasopiśmie wyróżnionym w JCR
- Published in:
-
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
no. 17,
edition 26,
pages 16907 - 16916,
ISSN: 1463-9076 - Language:
- English
- Publication year:
- 2015
- Bibliographic description:
- Zdrowowicz M., Chomicz L., Żyndul M., Wityk P., Rak J., Wiegand T., Hanson C., Adhikary A., Sevilla M.: 5-Thiocyanato-2′-deoxyuridine as a possible radiosensitizer: electron-induced formation of uracil-C5-thiyl radical and its dimerization// PHYSICAL CHEMISTRY CHEMICAL PHYSICS. -Vol. 17, iss. 26 (2015), s.16907-16916
- DOI:
- Digital Object Identifier (open in new tab) 10.1039/c5cp02081f
- Verified by:
- Gdańsk University of Technology
seen 136 times
Recommended for you
Intramolecular Proton Transfer in the Radical Anion of Cytidine Monophosphate Sheds Light on the Sensitivities of Dry vs Wet DNA to Electron Attachment-Induced Damage
- L. Chomicz-Mańka,
- A. Czaja,
- K. Falkiewicz
- + 11 authors
5-Selenocyanato and 5-trifluoromethanesulfonyl derivatives of 2′-deoxyuridine: synthesis, radiation and computational chemistry as well as cytotoxicity
- S. Makurat,
- M. Zdrowowicz,
- L. Chomicz-Mańka
- + 6 authors
H2O˙+ and OH+ reactivity versus furan: experimental low energy absolute cross sections for modeling radiation damage
- D. Ascenzi,
- E. Erdmann,
- P. Bolognesi
- + 9 authors