Next Article in Journal
Floral Scent Variation in the Heterostylous Species Gelsemium sempervirens
Next Article in Special Issue
The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity
Previous Article in Journal
Extraction Optimization, Structural Characterization, and Antioxidant Activities of Polysaccharides from Cassia Seed (Cassia obtusifolia)
Previous Article in Special Issue
Populations and Dynamics of Guanine Radicals in DNA strands—Direct versus Indirect Generation
Open AccessArticle

Why Does the Type of Halogen Atom Matter for the Radiosensitizing Properties of 5-Halogen Substituted 4-Thio-2′-Deoxyuridines?

1
Laboratory of Biological Sensitizers, Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland
2
Centre of Radiation Research and Technology, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Chryssostomos Chatgilialoglu
Molecules 2019, 24(15), 2819; https://doi.org/10.3390/molecules24152819
Received: 17 July 2019 / Revised: 30 July 2019 / Accepted: 31 July 2019 / Published: 2 August 2019
(This article belongs to the Special Issue Biomimetic Radical Chemistry and Applications)
Radiosensitizing properties of substituted uridines are of great importance for radiotherapy. Very recently, we confirmed 5-iodo-4-thio-2′-deoxyuridine (ISdU) as an efficient agent, increasing the extent of tumor cell killing with ionizing radiation. To our surprise, a similar derivative of 4-thio-2’-deoxyuridine, 5-bromo-4-thio-2′-deoxyuridine (BrSdU), does not show radiosensitizing properties at all. In order to explain this remarkable difference, we carried out a radiolytic (stationary and pulse) and quantum chemical studies, which allowed the pathways to all radioproducts to be rationalized. In contrast to ISdU solutions, where radiolysis leads to 4-thio-2’-deoxyuridine and its dimer, no dissociative electron attachment (DEA) products were observed for BrSdU. This observation seems to explain the lack of radiosensitizing properties of BrSdU since the efficient formation of the uridine-5-yl radical, induced by electron attachment to the modified nucleoside, is suggested to be an indispensable attribute of radiosensitizing uridines. A larger activation barrier for DEA in BrSdU, as compared to ISdU, is probably responsible for the closure of DEA channel in the former system. Indeed, besides DEA, the XSdU anions may undergo competitive protonation, which makes the release of X kinetically forbidden. View Full-Text
Keywords: radiosensitizers; stationary radiolysis; pulse radiolysis; modified nucleosides; cellular response radiosensitizers; stationary radiolysis; pulse radiolysis; modified nucleosides; cellular response
Show Figures

Graphical abstract

MDPI and ACS Style

Spisz, P.; Zdrowowicz, M.; Makurat, S.; Kozak, W.; Skotnicki, K.; Bobrowski, K.; Rak, J. Why Does the Type of Halogen Atom Matter for the Radiosensitizing Properties of 5-Halogen Substituted 4-Thio-2′-Deoxyuridines? Molecules 2019, 24, 2819.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop