TY  - JOUR
A1  - Schürmann, Robin Mathis
A1  - Tsering, Thupten
A1  - Tanzer, Katrin
A1  - Denifl, Stephan
A1  - Kumar, S. V. K.
A1  - Bald, Ilko
T1  - Resonant Formation of Strand Breaks in Sensitized Oligonucleotides Induced by Low-Energy Electrons (0.5-9 eV)
JF  - Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition
N2  - Halogenated nucleobases are used as radiosensitizers in cancer radiation therapy, enhancing the reactivity of DNA to secondary low-energy electrons (LEEs). LEEs induce DNA strand breaks at specific energies (resonances) by dissociative electron attachment (DEA). Although halogenated nucleobases show intense DEA resonances at various electron energies in the gas phase, it is inherently difficult to investigate the influence of halogenated nucleobases on the actual DNA strand breakage over the broad range of electron energies at which DEA can take place (<12 eV). By using DNA origami nanostructures, we determined the energy dependence of the strand break cross-section for oligonucleotides modified with 8-bromoadenine ((8Br)A). These results were evaluated against DEA measurements with isolated (8Br)A in the gas phase. Contrary to expectations, the major contribution to strand breaks is from resonances at around 7 eV while resonances at very low energy (<2 eV) have little influence on strand breaks.
KW  - cancer radiation therapy
KW  - dissociative electron attachment
KW  - DNA origami
KW  - DNA radiation damage
KW  - radiosensitizers
Y1  - 2017
U6  - https://doi.org/10.1002/anie.201705504
SN  - 1433-7851
SN  - 1521-3773
VL  - 56
SP  - 10952
EP  - 10955
PB  - Wiley-VCH
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - da Silva, Filipe Ferreira
A1  - Varella, Marcio T. do N.
A1  - Jones, Nykola C.
A1  - Hoffmann, Soren Vronning
A1  - Denifl, Stephan
A1  - Bald, Ilko
A1  - Kopyra, Janina
T1  - Electron-Induced Reactions in 3-Bromopyruvic Acid
JF  - Chemistry - a European journal
N2  - 3-Bromopyruvic acid (3BP) is a potential anticancer drug, the action of which on cellular metabolism is not yet entirely clear. The presence of a bromine atom suggests that it is also reactive towards low-energy electrons, which are produced in large quantities during tumour radiation therapy. Detailed knowledge of the interaction of 3BP with secondary electrons is a prerequisite to gain a complete picture of the effects of 3BP in different forms of cancer therapy. Herein, dissociative electron attachment (DEA) to 3BP in the gas phase has been studied both experimentally by using a crossed-beam setup and theoretically through scattering and quantum chemical calculations. These results are complemented by a vacuum ultraviolet absorption spectrum. The main fragmentation channel is the formation of Br- close to 0 eV and within several resonant features at 1.9 and 3-8 eV. At low electron energies, Br- formation proceeds through sigma* and pi* shape resonances, and at higher energies through core-excited resonances. It is found that the electron-capture cross-section is clearly increased compared with that of non-brominated pyruvic acid, but, at the same time, fragmentation reactions through DEA are significantly altered as well. The 3BP transient negative ion is subject to a lower number of fragmentation reactions than those of pyruvic acid, which indicates that 3BP could indeed act by modifying the electron-transport chains within oxidative phosphorylation. It could also act as a radio-sensitiser.
KW  - density functional calculations
KW  - dissociative electron attachment
KW  - drug discovery
KW  - gas-phase reactions
KW  - sensitizers
Y1  - 2019
U6  - https://doi.org/10.1002/chem.201806132
SN  - 0947-6539
SN  - 1521-3765
VL  - 25
IS  - 21
SP  - 5498
EP  - 5506
PB  - Wiley-VCH
CY  - Weinheim
ER  -