Scaling Complexity in the Study of Radiation Damage in Biomolecules

Abstract

Understanding biological radiation damage on the nanoscale is a major goal in Chemical Physics/Physical Chemistry, with implications in medicine and elucidating the molecular origins of life. A valuable tool for developing new insights involves drawing comparisons between the radiation responses of progressively more complex gas-phase biomolecules. While experimental studies of neutral nucleobases are prevalent, the literature diminishes sharply with increasing molecular complexity. This is linked to escalating thermal lability. In response, this thesis characterises, exploits, and develops a relatively new method, indirect laser-induced thermal desorption (ILTD), for the study of neutral gas- phase RNA/DNA constituents. We present the first in-depth study of ILTD for the production of pure targets of the nucleobase guanine and the nucleosides uridine, thymidine, 2′-deoxyuridine and 5- methyluridine. Except for thymidine, UV multi-photon ionisation (MPI) experiments demonstrated the efficacy of ILTD to produce viable targets without thermal decomposition. This inspired us to design and build a unique set-up for probing dissociative electron attachment (DEA), an important process in radiation damage of nucleic acids, to ILTD targets. The MPI experiments on uridine showed evidence for changes in isomeric populations as a function of ILTD conditions. Furthermore, they provided the first experimental evidence for the electronic excited state dynamics of uridine being sensitive to the molecule’s isomeric form prior to photo-excitation. This highlights the importance of developing methods to produce gas-phase targets that are structurally pure as well as unfragmented. Finally, the thesis presents an adapted reflectron time-of-flight mass spectrometry technique to analyse the metastable fragmentation and sequential fragmentation pathways. This revealed exceptionally rich metastable dissociation patterns of excited 3-aminophenol ions. We expect MPI-induced metastable dissociation to be highly sensitive to isomeric form, and hence to be a valuable tool in the future development of our research programme.