@article{KopyraWierzbickaTulwinetal.2021, author = {Kopyra, Janina and Wierzbicka, Paulina and Tulwin, Adrian and Thiam, Guillaume and Bald, Ilko and Rabilloud, Franck and Abdoul-Carime, Hassan}, title = {Experimental and theoretical studies of dissociative electron attachment to metabolites oxaloacetic and citric acids}, series = {International Journal of Molecular Sciences (IJMS)}, volume = {22}, journal = {International Journal of Molecular Sciences (IJMS)}, number = {14}, publisher = {MDPI}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms22147676}, pages = {14}, year = {2021}, abstract = {In this contribution the dissociative electron attachment to metabolites found in aerobic organisms, namely oxaloacetic and citric acids, was studied both experimentally by means of a crossed-beam setup and theoretically through density functional theory calculations. Prominent negative ion resonances from both compounds are observed peaking below 0.5 eV resulting in intense formation of fragment anions associated with a decomposition of the carboxyl groups. In addition, resonances at higher energies (3-9 eV) are observed exclusively from the decomposition of the oxaloacetic acid. These fragments are generated with considerably smaller intensities. The striking findings of our calculations indicate the different mechanism by which the near 0 eV electron is trapped by the precursor molecule to form the transitory negative ion prior to dissociation. For the oxaloacetic acid, the transitory anion arises from the capture of the electron directly into some valence states, while, for the citric acid, dipole- or multipole-bound states mediate the transition into the valence states. What is also of high importance is that both compounds while undergoing DEA reactions generate highly reactive neutral species that can lead to severe cell damage in a biological environment.}, language = {en} } @misc{KopyraWierzbickaTulwinetal.2021, author = {Kopyra, Janina and Wierzbicka, Paulina and Tulwin, Adrian and Thiam, Guillaume and Bald, Ilko and Rabilloud, Franck and Abdoul-Carime, Hassan}, title = {Experimental and theoretical studies of dissociative electron attachment to metabolites oxaloacetic and citric acids}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1156}, issn = {1866-8372}, doi = {10.25932/publishup-52182}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-521829}, pages = {16}, year = {2021}, abstract = {In this contribution the dissociative electron attachment to metabolites found in aerobic organisms, namely oxaloacetic and citric acids, was studied both experimentally by means of a crossed-beam setup and theoretically through density functional theory calculations. Prominent negative ion resonances from both compounds are observed peaking below 0.5 eV resulting in intense formation of fragment anions associated with a decomposition of the carboxyl groups. In addition, resonances at higher energies (3-9 eV) are observed exclusively from the decomposition of the oxaloacetic acid. These fragments are generated with considerably smaller intensities. The striking findings of our calculations indicate the different mechanism by which the near 0 eV electron is trapped by the precursor molecule to form the transitory negative ion prior to dissociation. For the oxaloacetic acid, the transitory anion arises from the capture of the electron directly into some valence states, while, for the citric acid, dipole- or multipole-bound states mediate the transition into the valence states. What is also of high importance is that both compounds while undergoing DEA reactions generate highly reactive neutral species that can lead to severe cell damage in a biological environment.}, language = {en} } @article{daSilvaVarellaJonesetal.2019, author = {da Silva, Filipe Ferreira and Varella, Marcio T. do N. and Jones, Nykola C. and Hoffmann, Soren Vronning and Denifl, Stephan and Bald, Ilko and Kopyra, Janina}, title = {Electron-Induced Reactions in 3-Bromopyruvic Acid}, series = {Chemistry - a European journal}, volume = {25}, journal = {Chemistry - a European journal}, number = {21}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0947-6539}, doi = {10.1002/chem.201806132}, pages = {5498 -- 5506}, year = {2019}, abstract = {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.}, language = {en} } @phdthesis{Vogel2018, author = {Vogel, Stefanie}, title = {Sequence dependency of photon and electron induced DNA strand breaks}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-419669}, school = {Universit{\"a}t Potsdam}, pages = {xii, 117}, year = {2018}, abstract = {Deoxyribonucleic acid (DNA) is the carrier of human genetic information and is exposed to environmental influences such as the ultraviolet (UV) fraction of sunlight every day. The photostability of the DNA against UV light is astonishing. Even if the DNA bases have a strong absorption maximum at around 260 nm/4.77 eV, their quantum yield of photoproducts remains very low 1. If the photon energies exceed the ionization energy (IE) of the nucleobases ( ̴ 8-9 eV) 2, the DNA can be severely damaged. Photoexcitation and -ionization reactions occur, which can induce strand breaks in the DNA. The efficiency of the excitation and ionization induced strand breaks in the target DNA sequences are represented by cross sections. If Si as a substrate material is used in the VUV irradiation experiments, secondary electrons with an energy below 3.6 eV are generated from the substrate. This low energy electrons (LEE) are known to induce dissociative electron attachment (DEA) in DNA and with it DNA strand breakage very efficiently. LEEs play an important role in cancer radiation therapy, since they are generated secondarily along the radiation track of ionizing radiation. In the framework of this thesis, different single stranded DNA sequences were irradiated with 8.44 eV vacuum UV (VUV) light and cross sections for single strand breaks (SSB) were determined. Several sequences were also exposed to secondary LEEs, which additionally contributed to the SSBs. First, the cross sections for SSBs depending on the type of nucleobases were determined. Both types of DNA sequences, mono-nucleobase and mixed sequences showed very similar results upon VUV radiation. The additional influence of secondarily generated LEEs resulted in contrast in a clear trend for the SSB cross sections. In this, the polythymine sequence had the highest cross section for SSBs, which can be explained by strong anionic resonances in this energy range. Furthermore, SSB cross sections were determined as a function of sequence length. This resulted in an increase in the strand breaks to the same extent as the increase in the geometrical cross section. The longest DNA sequence (20 nucleotides) investigated in this series, however, showed smaller cross section values for SSBs, which can be explained by conformational changes in the DNA. Moreover, several DNA sequences that included the radiosensitizers 5-Bromouracil (5BrU) and 8-Bromoadenine (8BrA) were investigated and the corresponding SSB cross sections were determined. It was shown that 5BrU reacts very strongly to VUV radiation leading to high strand break yields, which showed in turn a strong sequence-dependency. 8BrA, on the other hand, showed no sensitization to the applied VUV radiation, since almost no increase in strand breakage yield was observed in comparison to non-modified DNA sequences. In order to be able to identify the mechanisms of radiation damage by photons, the IEs of certain DNA sequences were further explored using photoionization tandem mass spectrometry. By varying the DNA sequence, both the IEs depending on the type of nucleobase as well as on the DNA strand length could be identified and correlated to the SSB cross sections. The influence of the IE on the photoinduced reaction in the brominated DNA sequences could be excluded.}, language = {en} } @article{SchuermannVogelEbeletal.2018, author = {Sch{\"u}rmann, Robin Mathis and Vogel, Stefanie and Ebel, Kenny and Bald, Ilko}, title = {The physico-chemical basis of DNA radiosensitization}, series = {Chemistry - a European journal}, volume = {24}, journal = {Chemistry - a European journal}, number = {41}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0947-6539}, doi = {10.1002/chem.201800804}, pages = {10271 -- 10279}, year = {2018}, abstract = {High-energy radiation is used in combination with radiosensitizing therapeutics to treat cancer. The most common radiosensitizers are halogenated nucleosides and cisplatin derivatives, and recently also metal nanoparticles have been suggested as potential radiosensitizing agents. The radiosensitizing action of these compounds can at least partly be ascribed to an enhanced reactivity towards secondary low-energy electrons generated along the radiation track of the high-energy primary radiation, or to an additional emission of secondary reactive electrons close to the tumor tissue. This is referred to as physico-chemical radiosensitization. In this Concept article we present current experimental methods used to study fundamental processes of physico-chemical radiosensitization and discuss the most relevant classes of radiosensitizers. Open questions in the current discussions are identified and future directions outlined, which can lead to optimized treatment protocols or even novel therapeutic concepts.}, language = {en} } @article{SchuermannTseringTanzeretal.2017, author = {Sch{\"u}rmann, Robin Mathis and Tsering, Thupten and Tanzer, Katrin and Denifl, Stephan and Kumar, S. V. K. and Bald, Ilko}, title = {Resonant Formation of Strand Breaks in Sensitized Oligonucleotides Induced by Low-Energy Electrons (0.5-9 eV)}, series = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition}, volume = {56}, journal = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1433-7851}, doi = {10.1002/anie.201705504}, pages = {10952 -- 10955}, year = {2017}, abstract = {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.}, language = {en} } @article{RackwitzKopyraDabkowskaetal.2016, author = {Rackwitz, Jenny and Kopyra, Janina and Dabkowska, Iwona and Ebel, Kenny and Rankovic, MiloS Lj. and Milosavljevic, Aleksandar R. and Bald, Ilko}, title = {Sensitizing DNA Towards Low-Energy Electrons with 2-Fluoroadenine}, series = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition}, volume = {55}, journal = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1433-7851}, doi = {10.1002/anie.201603464}, pages = {10248 -- 10252}, year = {2016}, abstract = {2-Fluoroadenine ((2F)A) is a therapeutic agent, which is suggested for application in cancer radiotherapy. The molecular mechanism of DNA radiation damage can be ascribed to a significant extent to the action of low-energy (<20 eV) electrons (LEEs), which damage DNA by dissociative electron attachment. LEE induced reactions in (2F)A are characterized both isolated in the gas phase and in the condensed phase when it is incorporated into DNA. Information about negative ion resonances and anion-mediated fragmentation reactions is combined with an absolute quantification of DNA strand breaks in (2F)A-containing oligonucleotides upon irradiation with LEEs. The incorporation of (2F)A into DNA results in an enhanced strand breakage. The strand-break cross sections are clearly energy dependent, whereas the strand-break enhancements by (2F)A at 5.5, 10, and 15 eV are very similar. Thus, (2F)A can be considered an effective radiosensitizer operative at a wide range of electron energies.}, language = {en} }