5-Thiocyanato-2′-deoxyuridine as a possible radiosensitizer: electron-induced formation of uracil-C5-thiyl radical and its dimerization - Publication - Bridge of Knowledge

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)

  • Photo of  Magdalena Zdrowowicz

    Magdalena Zdrowowicz

    • Uniwersytet Gdański/Wydział Chemii Chemii Fizycznej
  • Photo of  Lidia Chomicz

    Lidia Chomicz

    • Uniwersytet Gdański/Wydział Chemii Chemii Fizycznej
  • Photo of  Michał Żyndul

    Michał Żyndul

    • Uniwersytet Gdański/Wydział Chemii Chemii Fizycznej
  • Photo of dr inż. Paweł Wityk

    Paweł Wityk dr inż.

    • Uniwersytet Gdański/Wydział Chemii Chemii Fizycznej
  • Photo of Prof. Janusz Rak

    Janusz Rak Prof.

    • Uniwersytet Gdański/Wydział Chemii Chemii Fizycznej
  • Photo of  Tyler Wiegand

    Tyler Wiegand

    • Oakland Univeristy
  • Photo of  Cameron Hanson

    Cameron Hanson

    • Oakland Univeristy
  • Photo of  Amitava Adhikary

    Amitava Adhikary

    • Oakland Univeristy
  • Photo of  Michael Sevilla

    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 90 times

Recommended for you

Meta Tags