How chain length influences x-ray-induced fragmentation of iodine-doped DNA oligomers

Objective. Incorporating iodine into deoxyribonucleic acid (DNA) bases offers a strategy to enhance radiotherapy. The iodine increases the photoabsorption cross-section and can promote DNA disruption and cell death in cancerous tissue. In this study, we investigate the local fragmentation mechanisms of iodinated DNA and the spatial extent of damage propagation following photoactivation. Approach. Single-stranded DNA oligonucleotides consisting of 2–5 bases, in which the methyl group of thymine is substituted with an iodine atom, were irradiated with synchrotron x-rays above the iodine L-shell ionisation threshold (4900 eV). Fragmentation patterns were extracted by subtracting background spectra obtained below the threshold (4500 eV), and the results were complemented by Born–Oppenheimer molecular dynamics simulations to resolve bond breaking at the atomic level. Main results. We find that longer oligonucleotide chains predominantly generate larger, high- m/z fragments, while shorter sequences produce a wider variety of small fragments. Backbone cleavage is observed in all sequences, with phosphate- and sugar-based ions dominating the spectra. Bond scission extends up to five bases from the iodination site, with the heaviest stable fragment containing two bases. Significance. Suppose this effect is extrapolated to genomic DNA, which includes about 29.5% thymine. In that case, the amount of thymine replaced by iodinated uracil can help estimate the extent of DNA damage that might occur during radiation therapy using iodine as a radiosensitiser.