Chemistry triggerred by high-energy photons – HighEneCh

Detection of radicals will be based on chemical scavenging methods that will be used to quantify the production of OH and HO2 radicals, under different irradiation conditions. In the first experiments, irradiation studies will be carried out in part with an up-graded version of an existing movable experimental set-up (IRAD set-up), which be upgraded with a microfluidic cell, and used under anaerobic conditions.
Photo/Auger electron spectroscopy studies of liquids will utilize a new portable apparatus (MultiSpec Set-up), where a recycling liquid microjet will be used in vacuum. Recovering the irradiated sample is crucial for our project to be able to perform off-line analytical measurements (fluorescence yield, mass spectrometry) on the same sample measured by electron spectroscopy. We also plan to recycle sample in a closed loop system in order to progressively increase the average dose and follow its chemical evolution. Electron coincidence techniques will be used on the liquids to associate the photoelectron and Auger spectra, and thus have a better understanding of the effects of the environment during the decay processes of the initial core hole.
A close collaboration with theoreticians will be a valuable component of the consortium. We will investigate the early stages of the dissociation of core ionized water or sugar-phosphate molecules, embedded in liquid water, at the femto to picosecond time scale, using ab initio Molecular Dynamics (MD) simulation.

The modifications caused by solvation on the electronic structure of a model protein, bovine serum albumin (BSA), and the role played by water in the delocalization of the hole in the protein were highlighted. A methodology for measuring the energy diagram of a protein has been established. The energy distributions of the Auger electrons emitted in solution could be determined as a function of the chemical specificity of its linked photoelectrons in different molecules thanks to coincidence measurements. A new microfluidic cell for irradiation allowed to determine the production rates of OH° and superoxide (HO2) radicals and to confirm, thanks to the theoretical support, that the X-rays behave as particles with high linear energy transfer.

With the HighEneCh project, our consortium will make significant steps towards understanding of the fundamental chemical mechanisms triggered by core ionization in pure water and water/biomolecule mixtures irradiated by soft and hard x-rays. Our project should bring a comprehensive view of neutral and charged species created by this irradiation. It will provide important experimental verifications for simulations of the direct and indirect processes, which will both influence the biological damage.
The HighEneCh project will provide research teams interested in the fundamental chemical mechanisms which occur during irradiation, two well-characterised set-ups (IRAD and MultiSpec) and robust detection schemes for detecting neutral and charged particles. There is no doubt that the HighEneCh project will trigger new collaborations and new studies on more complex systems.
The results of the HighEneCh project will also result in fundamental new insights into micro/nano-dosimetry. In the long term, our protocols and techniques should be valuable in evaluating the efficacy of nano-agents in solution for example, the relative susceptibility of a nano-agent to reduce some reactive oxygen species in the solution. These fundamental studies will help to provide a solid foundation of radiation chemistry, which could lead to more efficient personalized medicine.

In the article [Int. J. of Mol. Sciences, 23(15): art.no. 8227. (2022)] a comparison of electron spectroscopy of solvated and solid BSA has been performed providing information on the modification of its electronic structure by water molecules. The article [accepted in PCCP] presents the new electron spectrometer and the first results of photo/Auger electron coincidence measurements on small solvated molecules. The article [J of Phys. Chem. A., 124(10): 1896-1902. (2020)] shows the complementarity between Monte-Carlo simulations and soft X-ray irradiation allowing a description of the radiochemistry caused by sub-keV electrons. The article [J. of Syn. Rad., 28(3): 778-789. (2021)] presents our microfluidic cell for irradiation and details the important experimental parameters to be considered and confirms the results obtained with a standard irradiation.

Huart L., Fournier M., Dupuy R., Vacheresse R., Reinhardt M., Cubaynes D., Céolin D., Hervé du Penhoat M.A., Renault J.P., Guigner J.-M., Kumar A., Lutet-Toti B., Bozek J., Ismail I., Journel L., Lablanquie P., Penent F., Nicolas C. and PalaudouxFirst J. “(e,e) coincidence measurements on solvated sodium benzoate in water using a magnetic bottle time-of-flight spectrometer”, , accepted to PCCP, 2022.

Renault, J.P., Huart, L., Milosavljevic, A.R., Bozek, J.D., Palaudoux, J., Guigner, J.M., Marichal, L., Leroy, J., Wien, F., Hervé Du Penhoat, M.A., Nicolas, C. «Electronic Structure and Solvation Effects from Core and Valence Photoelectron Spectroscopy of Serum Albumin« International Journal of Molecular Sciences., 23(15): art.n° 8227. (2022).

«Effets d’ionisation en couche interne sur des molécules d’intérêt biologique en milieu aqueux«: thèse de Lucie Huart sous la direction de Marie-Anne Hervé du Penhoat, Jean-Philippe Renault et de Christophe Nicolas. - Sorbonne université. Soutenue le 17 janvier 2022.

Huart, L., Nicolas, C., Hervé du Penhoat, M.A., Guigner, J.M., Gosse, C., Palaudoux, J., Lefrançois, S., Mercere, P., Dasilva, P., Renault, J.P., Chevallard, C. «A microfluidic dosimetry cell to irradiate solutions with poorly penetrating radiations: a step towards online dosimetry for synchrotron beamlines« Journal of Synchrotron Radiation., 28(3): 778-789. (2021).

Huart, L., Nicolas, C., Kaddissy, J.A., Guigner, J.M., Touati, A., Politis, M.F., Mercere, P., Gervais, B., Renault, J.P., Hervé du Penhoat, M.A. «Soft X-ray Radiation and Monte Carlo Simulations: Good Tools to Describe the Radiation Chemistry of Sub-keV Electrons« Journal of Physical Chemistry A., 124(10): 1896-1902. (2020).

The HighEneCh ANR project aims to initiate and organize collaborative work between specialists of electron spectroscopy and instrumentation at large-scale facilities (SOLEIL, UPMC – LCP-MR), radiation chemistry (CEA - NIMBE), microfluidic systems (CEA – NIMBE) and ab initio molecular dynamics simulations (UPMC - IMPMC), with the goal of extending the boundaries of fundamental knowledge of the different mechanisms involved in the chemistry in aqueous environments triggered by high-energy photons.
Using complementary approaches, the HighEneCh project consortium wants, over the 48 months’ duration of the project, to achieve a global view of the radiolysis of pure water and of water/biomolecule mixtures irradiated with soft X-ray and hard X-ray synchrotron light, with a special focus on the chemical effects of core ionizations. Irradiation with high-energy photons (x-ray) produces charged and neutral species which can both influence the production of the damage caused by the radiation via direct and indirect processes, respectively. The original approach of our consortium is to combine state-of-the-art quantification methods for the detection of radical species with photo/Auger electron spectroscopy on liquids, supported by ab initio molecular dynamics simulations to elucidate the fundamental mechanisms of the interaction of high energy photons with biological material surrounded by a liquid.
Detection of radicals will be based on chemical scavenging methods that will be used to quantify the production of OH and HO2 radicals, under different irradiation conditions. In the first experiments, irradiation studies will be carried out in part with an up-graded version of an existing movable experimental set-up (IRAD set-up), which be upgraded with a microfluidic cell, and used under anaerobic conditions.
Photo/Auger electron spectroscopy studies of liquids will utilize a new portable apparatus (MultiSpec Set-up), where a recycling liquid microjet will be used in vacuum. Recovering the irradiated sample is crucial for our project to be able to perform off-line analytical measurements (fluorescence yield, mass spectrometry) on the same sample measured by electron spectroscopy. We also plan to recycle sample in a closed loop system in order to progressively increase the average dose and follow its chemical evolution. Electron coincidence techniques will be used on the liquids to associate the photoelectron and Auger spectra, and thus have a better understanding of the effects of the environment during the decay processes of the initial core hole.
Our studies will extend from pure water to solutions of sugar phosphates such as 5 ribose phosphate and 2-deoxyribose 5-monophosphate, a biomimetic molecule of the DNA backbone.
A close collaboration with theoreticians will be a valuable component of the consortium. We will investigate the early stages of the dissociation of core ionized water or sugar-phosphate molecules, embedded in liquid water, at the femto to picosecond time scale, using ab initio Molecular Dynamics (MD) simulation. To support the experimental findings for the production of superoxide radicals in pure water, we will first model the dynamics induced by an oxygen-K ionization, starting from configurations in which one water molecule is doubly ionized and another one, localized within one nanometer, is singly ionized. Such an event is highly probable since, after Auger decay, the core-ionized water molecule will carry a double vacancy. Moreover, the photo and Auger electrons are ejected with a few hundred electronvolts kinetic energy and can ionize a neighbouring water molecule with a high probability since their mean free path is only a few nanometers in water. The results will be used as input data for the Kinetic Monte-Carlo simulation to extend to the chemistry occurring on a time scale of microseconds.