Collision Studies with Electro-Sprayed Biomolecules

Abstract

In this PhD thesis, the fragmentation of prototype radiosensitizer molecules for cance radio- and chemo-therapy is investigated through gas-phase collision experiments. The main goal is to extend the current knowledge on the radiosensitization mechanism by assessing the formation of reactive species, ions and neutral radicals, which may lead to DNA damage during the early stages of radiation damage. In the first part, a collision-induced dissociation study with protonated ronidazole carried out with a home-built electrospray ionization source coupled to a double-focusing mass spectrometer is presented. The main fragmentation pathway results from an intramolecular proton transfer reaction followed by release of neutral – NH2CO2H fragment. This reaction was demonstrated in low- and high-energy CID experiments with partially deuterated ronidazole supported by DFT quantum chemical calculations. The second part of the thesis focuses on low-energy electron interactions with 5-trifluoromethanesulfonyluracil (OTfU), a modified pyrimidine, and benzaldehyde, a compound used in anti-cancer clinical trials. Crossed electron-molecular beam setups coupled with a quadrupole mass spectrometer were employed to identify the formed fragment anions, and to measure anion efficiency curves as function of the incident electron energy. In dissociative electron attachment (DEA) to OTfU, the triflate anion (OTF-), along with the reactive uracil-5-yl radical was identified as the dominant anionic fragment. The efficient decomposition of OTfU into reactive species upon electron attachment endorses its potential as a radiosensitizer. For benzaldehyde, in addition to the molecular anion detection, further nine fragment anions were observed with modest DEA cross sections of about 10−24 − 10−23 m2. The study with partially deuterated benzaldehyde showed that the dehydrogenation of benzaldehyde is selective with respect to the incident electron energy. The formation of resonances was also theoretically investigated by electron scattering calculations, and a quantum chemical study predicted the thermochemical thresholds for the observed fragments. The insights gained in this PhD thesis may contribute for a better understanding on radiation damage, which is of paramount importance for the design of new radiosensitizer drugs, as well as for the development of more efficient cancer treatments.