Ring Formation and Hydration Effects in Electron Attachment to Misonidazole

Abstract

We study the reactivity of misonidazole with low-energy electrons in a water environment combining experiment and theoretical modelling. The environment is modelled by sequential hydration of misonidazole clusters in vacuum. The well-defined experimental conditions enable computational modeling of the observed reactions. While the NO2− dissociative electron attachment channel is suppressed, as also observed previously for other molecules, the OH− channel remains open. Such behavior is enabled by the high hydration energy of OH− and ring formation in the neutral radical co-fragment. These observations help to understand the mechanism of bio-reductive drug action. Electron-induced formation of covalent bonds is then important not only for biological processes but may find applications also in technology.

An intense source for cold cluster ions of a specific composition

“…[86][87][88][89][90][91][92][93] Clusters of biomolecules can be microsolvated with water which is an important issue to simulate life-like conditions and difficult to achieve with other methods. [104][105][106][107]…”

Electron Attachment Studies with the Potential Radiosensitizer 2-Nitrofuran

“…Notable is also the absence of the OH − fragment anion, which was observed in DEA studies with the radiosensitiser misonidazole [ 19 ]. It was predicted that the formation of OH − remains upon solvation [ 54 ], in contrast to NO 2 − , which was observed as an abundant fragment anion only under isolated conditions in the gas phase.…”

Interaction of low-energy electrons with radiosensitizers

“…This may be caused by the preferred hydration of the MISO over the hydroxyl group and predissociation as supported by theoretical calculations in the work. 204 Computational modeling also reveals that TNI fragmentation via OH loss can be accompanied by significant rearrangement of the neutral counterpart forming ring structures and increasing the exothermicity of the process in solution.…”

“…202 The products of such interaction as well as the interactions with LEE electrons in the (0–10 eV) can be understood based on the experiments in the gas phase 203 and the microhydrated environment. 204 Similar to imidazole, two energy ranges for electron attachment have been identified, where the 0 eV attachment leads to the formation of parent anion while 2–4 eV shape resonances lead to the variety of the fragment anions dominated by the NO 2 bond cleavage. In contrast to nimorazole, MISO fragmentation upon interaction with LEEs seems not to be fully suppressed by hydration, but OH − channel remains open.…”