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 The effectiveness of radiotherapy relies on microscopic processes where atomic bonds are broken or formed in response to X-ray radiation. To understand and improve the therapeutic outcomes, it is essential to study these interactions on a molecular level, particularly for radiosensitising agents in that could enhance DNA damage in cancer cells. This work investigates the fragmentation dynamics of halogenated molecules in gas phase after deep core ionisation by X-rays and positive charge accumulation.

We used synchrotron experiments with mass spectrometry and Born-Oppenheimer based molecular dynamics simulations to study how molecules respond after being ionised at different photoabsorption edges. Nitroimidazole-based molecules doped with halogen atoms show similar production of fragments during ionisation of low-Z elements. A consistent high ion yield of reactive species such as NO₂⁺ and NO⁺ is observed, known to contribute to cellular damage. Ionisation of the halogen atoms produce energetic single-atom fragments, as measured in coincidence with photoelectrons. Production of this fragments depend on the final charge state of the molecule. Our simulations indicate that these fragments travel only short distances in water, promoting highly localised damage near the ionisation site. Introducing a water molecule into a radiosensitising system alters fragmentation in a subtle way. Water molecules enhance the release of halogen ions however, full atomisation of the molecule is the most dominant process. These findings help bridge the gap between isolated molecular studies and biological conditions.

Incorporating iodine-doped deoxyuridine (IUdR) into DNA reveal strong enhancements in fragmentation of the DNA-backbone at ionisation energies of deep core levels in the iodine atom. Our simulations showed that small reactive fragments, particularly those classified as reactive oxygen species (ROS), are formed. Fragmentation patterns change depending on the oligonucleotide chain length. Bond scission was observed several bases away from the iodine site, suggesting that core holes and resulting radiation damage migrate along the backbone of the oligonucleotide.

To model core hole localisation following X-ray ionisation, new simulation tools based on Born-Oppenheimer molecular dynamics have been developed. This enables a more accurate prediction of non-symmetric fragmentation and charge localisation in small molecules. These insights advance our understanding of molecular-level radiosensitisation and its relevance to radiotherapy.