Interaction of Vacuum UV radiation (6 - 12 eV) with complex DNA targets
Theoretical Chemistry: Electronic Structure, Dynamics, Simulation
Final Report Abstract
The interaction of UV light with DNA is very well explored with respect to the lowest electronic π-π* transition of the nucleobases located at around 4.7 eV (i.e. 260 nm), which can result in DNA damage products such as pyrimidine dimers. Other forms of severe DNA radiation damage such as strand breaks are typically expected to be associated with ionization of the DNA taking place at higher energies (8 – 10 eV), although single strand breaks have already been observed below the ionization threshold. The goal of the present project was to elucidate the electronic properties of well-defined DNA sequences in a joint experimental and theoretical approach. By using DNA origami technology we have determined the absolute cross sections of VUV photon induced single strand breaks of different DNA sequences (such as 5’-d(T12), 5’- d(A12), 5’-d(G12), 5’-d(C12)) at a photon energy of 8.44 eV (corresponding to the ionization potential of the adenine nucleobase) at the synchrotron SOLEIL. The values are approximately two orders of magnitude smaller than those obtained from electron irradiation in a similar energy range, but the process possesses a high quantum yield. In addition to homonucleotide sequences we have also studied sequences containing radiosensitizers such as 5-bromouracil and 8-bromoadenine. Such radiosensitizers are developed to be used in cancer radiation therapy, and in the present project we could reveal important mechanistic insight into their photosensitizing properties and the corresponding strand break mechanisms. As the strand breakage is most likely associated to ionization of the DNA we have also used a novel approach to determine the ionization potential of different DNA sequences. For this, we have trapped oligonucleotide ions in an ion trap and irradiated with photons with varying energy below and above the corresponding ionization energy. By recording tandem mass spectra we could determine the ionization potential of well-defined charged oligonucleotide sequences. Also these experiments have been carried out at the synchrotron SOLEIL. The obtained values were compared to ionization potentials determined by density functional theory (DFT).
Publications
- Long-Range Corrected DFT MeetsGW: Vibrationally Resolved Photoelectron Spectra from First Principles. Journal of Chemical Theory and Computation 11 2015, 5391-5400
L. Gallandi and T. Körzdörfer
(See online at https://doi.org/10.1021/acs.jctc.5b00820) - Accurate Ionization Potentials and Electron Affinities of Acceptor Molecules II: Non-Empirically Tuned Long-Range Corrected Hybrid Functionals. Journal of Chemical Theory and Computation 12 2016, 605-614
L. Gallandi, N. Marom, P. Rinke, and T. Körzdörfer
(See online at https://doi.org/10.1021/acs.jctc.5b00873) - The physico-chemical basis of DNA radiosensitization - Implications for cancer radiation therapy. Chem. Eur. J. 2018, 24, 10271
R. Schürmann, S. Vogel, K. Ebel
(See online at https://doi.org/10.1002/chem.201800804) - SOLEIL Highlights (Annual Report) 2019: Vacuum-UV and Low-Energy Electron-Induced DNA Strand Breaks monitored using DNA origami pp. 48-49
Stefanie Vogel, Kenny Ebel, Robin M. Schürmann, Christian Heck, Till Meiling, Aleksandar R. Milosavljevic, Alexan Giuliani, Ilko Bald
(See online at https://doi.org/10.1002/cphc.201801152) - Vacuum-UV and Low-Energy Electron Induced DNA Strand Breaks – Influence of the DNA Sequence and Substrate. ChemPhysChem 2019, 20, 823-830
S. Vogel, K. Ebel, R. Schürmann, C. Heck, T. Meiling, A. Milosavljević, A. Giuliani, I. Bald
(See online at https://doi.org/10.1002/cphc.201801152) - Vacuum-UV induced DNA strand breaks - influence of the radiosensitizers 5- bromouracil and 8-bromoadenine. Phys. Chem. Chem. Phys., 2019, 21, 1972
S. Vogel, K. Ebel, C. Heck, R. Schürmann, A. Milosavljević, A. Giuliani, I. Bald
(See online at https://doi.org/10.1039/C8CP06813E)
