TY  - GEN
A1  - Bald, Ilko
A1  - Kopyra, Janina
A1  - Keller, Adrian
T1  - On the role of fluoro-substituted nucleosides in DNA radiosensitization for tumor radiation therapy
N2  - Gemcitabine (2′,2′-difluorocytidine) is a well-known radiosensitizer routinely applied in concomitant chemoradiotherapy. During irradiation of biological media with high-energy radiation secondary low-energy (<10 eV) electrons are produced that can directly induce chemical bond breakage in DNA by dissociative electron attachment (DEA). Here, we investigate and compare DEA to the three molecules 2′-deoxycytidine, 2′-deoxy-5-fluorocytidine, and gemcitabine. Fluorination at specific molecular sites, i.e., nucleobase or sugar moiety, is found to control electron attachment and subsequent dissociation pathways. The presence of two fluorine atoms at the sugar ring results in more efficient electron attachment to the sugar moiety and subsequent bond cleavage. For the formation of the dehydrogenated nucleobase anion, we obtain an enhancement factor of 2.8 upon fluorination of the sugar, whereas the enhancement factor is 5.5 when the nucleobase is fluorinated. The observed fragmentation reactions suggest enhanced DNA strand breakage induced by secondary electrons when gemcitabine is incorporated into DNA.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - paper 167 
KW  - low-energy electrons
KW  - single-strand breaks
KW  - gas-phase
KW  - chemoradiation therapy
KW  - molecular-mechanisms
KW  - resonant formation
KW  - damage
KW  - attachment
KW  - drugs
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-73412
SP  - 6825
EP  - 6829
ER  - 
TY  - JOUR
A1  - Bald, Ilko
A1  - Keller, Adrian
A1  - Kopyra, Janina
T1  - On the role of fluoro-substituted nucleosides in DNA radiosensitization for tumor radiation therapy
JF  - RSC Advances : an international journal to further the chemical sciences
N2  - Gemcitabine (2′,2′-difluorocytidine) is a well-known radiosensitizer routinely applied in concomitant chemoradiotherapy. During irradiation of biological media with high-energy radiation secondary low-energy (<10 eV) electrons are produced that can directly induce chemical bond breakage in DNA by dissociative electron attachment (DEA). Here, we investigate and compare DEA to the three molecules 2′-deoxycytidine, 2′-deoxy-5-fluorocytidine, and gemcitabine. Fluorination at specific molecular sites, i.e., nucleobase or sugar moiety, is found to control electron attachment and subsequent dissociation pathways. The presence of two fluorine atoms at the sugar ring results in more efficient electron attachment to the sugar moiety and subsequent bond cleavage. For the formation of the dehydrogenated nucleobase anion, we obtain an enhancement factor of 2.8 upon fluorination of the sugar, whereas the enhancement factor is 5.5 when the nucleobase is fluorinated. The observed fragmentation reactions suggest enhanced DNA strand breakage induced by secondary electrons when gemcitabine is incorporated into DNA.
KW  - low-energy electrons
KW  - single-strand breaks
KW  - gas-phase
KW  - chemoradiation therapy
KW  - molecular-mechanisms
KW  - resonant formation
KW  - damage
KW  - attachment
KW  - drugs
Y1  - 2014
U6  - https://doi.org/10.1039/C3RA46735J
SN  - 2046-2069
VL  - 4
IS  - 13
SP  - 6825
EP  - 6829
PB  - Royal Society of Chemistry
ER  -