TY - JOUR A1 - Schürmann, Robin A1 - Vogel, Stefanie A1 - Ebel, Kenny A1 - Bald, Ilko T1 - The physico-chemical basis of DNA radiosensitization: Implications for cancer radiation therapy N2 - High-energy radiation is used in combination with radiosensitizing therapeutics to treat cancer. The most common radiosensitizers are halogenatednucleo-sides and cisplatin derivatives, and recently also metal nanoparticles have been suggested as potentialradiosensitizing agents. The radiosensitizingaction of these compounds can at least partly be ascribed to an enhancedreactivity towards secondary low-energy electrons generated along the radiation track of the high-energyprimary radiation, or to an additional emission of secondary reactive electrons close to the tumor tissue. This is referred to as physico-chem ical radiosensitization. In this Conceptarticle we presentcurrent experimental methodsused to study fundamentalprocesses 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 therapeuticconcepts. KW - DNA KW - Radiosensitization KW - Radiation damage KW - Low energy electrons PY - 2018 DO - https://doi.org/10.1002/chem.201800804 SN - 1521-3765 SN - 0947-6539 VL - 24 IS - 41 SP - 10271 EP - 10279 PB - WILEY AN - OPUS4-45742 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Schürmann, Robin A1 - Tanzer, Katrin A1 - Dąbkowska, Iwona A1 - Denifl, Stephan A1 - Bald, Ilko T1 - Stability of the parent anion of the potential radiosensitizer 8 ‑ Bromoadenine formed by low-energy (<3 eV) electron attachment N2 - 8-Bromoadenine (8BrA) is a potential DNA radiosensitizer for cancer radiation therapy due to its efficient interaction with low-energy electrons (LEEs). LEEs are a short-living species generated during the radiation damage of DNA by high-energy radiation as it is applied in cancer radiation therapy. Electron attachment to 8BrA in the gas phase results in a stable parent anion below 3 eV electron energy in addition to fragmentation products formed by resonant exocyclic bond cleavages. Density functional theory (DFT) calculations of the 8BrA– anion reveal an exotic bond between the bromine and the C8 atom with a bond length of 2.6 Å, where the majority of the charge is located on bromine and the spin is mainly located on the C8 atom. The detailed understanding of such long-lived anionic states of nucleobase analogues supports the rational development of new therapeutic agents, in which the enhancement of dissociative electron transfer to the DNA backbone is critical to induce DNA strand breaks in cancerous tissue. KW - Dissociative electron attachment KW - DNA damage KW - Radiosensitization KW - Mass spectrometry PY - 2017 DO - https://doi.org/10.1021/acs.jpcb.7b02130 SN - 1520-6106 VL - 121 IS - 23 SP - 5730 EP - 5734 AN - OPUS4-40963 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -