Report on precursor synthesis and related infrared spectroscopy measurements

Deliverable D10.6 Report on precursor synthesis and related infrared spectroscopy measurements This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101008571 (PRISMAP). This document reflects only the view of the author(s). The Agency is not responsible for any use that may be made of the information it contains. Deliverable D10.6 ii Project Acronym PRISMAP Project Title The European medical isotope programme: Production of high purity isotopes by mass separation Grant Agreement No. 101008571 Topic INFRAIA-02-2020: Integrating Activities for Starting Communities Project start date 01 May 2021 Nature Report Dissemination level Public Due date M30 Date of delivery M31 Lead partner CERN Contributing partners KULeuven Authors Thomas Elias Cocolios (KULeuven), Charlotte Duchemin, Edgars Mamis, Thierry Stora (CERN) Reviewers Sebastian Rothe (CERN), Mattia Manzolaro (INFN) Point of Contact Thomas Elias Cocolios Institution KULeuven E-mail [email protected] Phone +32 16 32 31 16 © PRISMAP 2021. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. Deliverable D10.6 iii Revision History Version Date Author Comment 0.1 27.09.2023 T. E. Cocolios with the input of P. Ferrari Skeleton draft, context, content, results 02 13.10.2023 T. E. Cocolios Final content and discussion 0.4 31.10.2023 C. Duchemin, E. Mamis, T. Stora, P. Dyson, Introduction and chemical synthesis 0.5 01.11.2023 M. Manzolaro, S. Rothe, K. Leufgen Review 0.6 02.11.2023 C. Duchemin, T. Stora Corrections and completions 0.7 02.11.2023 V. Gobry, K. Leufgen Review, completions and formatting 0.9 06.11.2023 T. Stora, K. Leufgen Corrections and completions. Version for review by the general assembly 1.0 08.11.2023 K. Leufgen Final version, approved by the coordinator and the general assembly Deliverable D10.6 iv Contents Abbreviations, Participant short names v ... v Abbreviations v … v Participant short names v List of Figures vii …... vii // Keep this line in place. It is need to fix a Word-bug in the TOC. vii … vii - vii Summary 1 … 1 // Keep this line in place. It is need to fix a Word-bug in the TOC. 1 1. Context 2 2. Medical Sc radionuclide production from isotopically enriched target materials 2 3. Methodology 6 4. Results 7 4.1 Raw data results 7 4.2 Infrared spectroscopy and isotope shifts 8 5. Conclusions and outlook 9 … 9 Deliverable D10.6 v Abbreviations, Participant short names ... Abbreviations … amu atomic mass units DFT Density Functional Theory FELIX Free Electron Lasers for Infrared eXperiments FWHM Full Width at Half Maximum IR Infrared IRMPD Infrared Multiple Photon Dissociation Spectroscopy IVR Infrared Vibrational energy Redistribution Nd:YAG Neodymium-dopped Yttrium Aluminium Garnet Participant short names CERN European organization for nuclear research NPL National Physical Laboratory PSI Paul Scherrer Institut CEA Commissariat à l’énergie atomique et aux énergies alternatives IST-ID Associação do Instituto Superior Técnico para a IST-ID Investigação e Desenvolvimento DTU Danmarks Tekniske Universitet CHUV Centre hospitalier universitaire vaudois GANIL Grand Accélérateur National d’Ions Lourds SCK CEN Studiecentrum voor Kernenergie / Centre d’étude de l’énergie nucléaire ARRONAX Groupement d’intérêt public ARRONAX ESS European spallation source ERIC TUM Klinikum rechts der Isar der technischen Universität München KULeuven KU Leuven MedAustron Entwicklungsund Betriebsgesellschaft MedAustron GmbH SCIPROM SCIPROM Sàrl MUI Medizinische Universität Innsbruck ILL Institut Max von Laue – Paul Langevin JRC JRC -Joint Research CentreEuropean Commission NCBJ Narodowe Centrum Badań Jądrowych GSI GSI Helmholtzzentrum fr Schwerionenforschung GmbH LU Latvijas Universitāte Deliverable D10.6 vi INFN Istituto Nazionale di Fisica Nucleare UiO Universitetet i Oslo Deliverable D10.6 vii List of Figures …... // Keep this line in place. It is need to fix a Word-bug in the TOC. … - Figure 1. Sc-43 production cross section on enriched Ca-43 via (p,n) reaction. 3 Figure 2. Sc-44m (left) and Sc-44g (right) cross sections from Ca-44(p,n) reaction 4 Figure 3. Sc-44m (left) and Sc-44g (right) cross section from Ca-44(d,2n) reaction (ref DUCHEMIN et al, 2015 https://iopscience.iop.org/article/10.1088/0031-9155/60/17/6847/pdf) 4 Figure 4. Cross-sections of the Ti-48(p,2p)47Sc nuclear reaction (ref http://dx.doi.org/10.1007/BF01421692, http://dx.doi.org/10.1103/PhysRevC.11.541 ) 5 Figure 5. Cross-sections of the Ca-48(p,2n)47Sc nuclear reaction (http://dx.doi.org/10.1016/j.apradiso.2018.10.015, http://dx.doi.org/10.1016/00295582(63)90527-3 ) 5 Figure 6. Cross-sections of the natV(p,x)47Sc nuclear reaction http://dx.doi.org/10.1007/s10967-01906844-8 6 Figure 7. Schematic representation of the experimental setup, composed of a laser desorption source and a reflectron time-of-flight mass spectrometer. A Xe/Ar cell pumped with the third harmonic of a Nd:YAG laser (355 nm) is used to generate 118 nm laser light, used for ionization. The counter propagating infrared laser light of the free electron laser FELIX resonantly excites vibrational modes of the neutral molecular species. 7 Figure 8. Typical mass spectrum of ionized calcium hexafluoroacetylacetonate molecules in a molecular beam. The inset presents a zoom in around the 454 amu mass peak. 8 Figure 9. Left: Experimental infrared spectrum of C10H2CaF12O4 in a molecular beam of Ar, for the peak in mass spectra corresponding to 40Ca. Right: Vibrational spectrum of [40Ca]C10H2CaF12O4, computed by DFT. The computed spectrum is constructed by assuming Gaussian functions around each vibrational mode, with a FWHM resembling the linewidth of FELIX (10% of each central wavelength). The inset presents the molecular geometry. 8 Summary … // Keep this line in place. It is need to fix a Word-bug in the TOC. According to the PRISMAP Description of Action, D10.6 is dedicated to the “Synthesis of the appropriate molecular precursors containing Ca and Ti and the related FTIR spectra measurements”, towards the application of laser-enhanced isotopically selective condensation for the enrichment of Ca and Ti radionuclides. As calcium hexafluoroacetylacetonate (C10H2CaF12O4) is commercially available, it has been procured externally for this purpose and characterised towards its planned use. Gas-phase infrared spectroscopy was employed to investigate the vibrational modes of calcium hexafluoroacetylacetonate (C10H2CaF12O4) in the wide wavenumber range from 550 to 1700 cm-1. The measured spectrum agrees well with previous density functional theory calculations, allowing a targeted laser excitation within PRISMAP at 490 cm-1, in order to resonantly excite a Ca isotope sensitive vibration. This demonstrates that this commercially available compound is appropriate for the sought-out application and that dedicated synthesis is thus not required. A similar approach may now be followed for Ti-containing molecules, where we need first to identify a suitable stable molecule, then perform the associated DFT calculations, perform the synthesis if no commercial compound can be identified, and finally verify those with infrared light spectroscopy. Deliverable D10.6 2 1. Context As previously reported in Deliverable D10.5, medical radionuclide production depends upon the availability of enriched material for targets, many of which are currently scarce, and for which Europe faces a strong dependency on external partners. More specifically, towards the production of 43,44,47Sc radionuclides for theranostics applications, the enrichment of calcium and titanium is being explored within PRISMAP. The production of medically relevant radionuclides used in theranostics applications can proceed from target irradiation at cyclotrons or in neutron reactors. Target enrichment from the starting natural element, together with the irradiation characteristics will ultimately determine the production yield and radionuclidic purity achieved. Target enrichment is therefore an important factor. In our previous deliverable (D10.5 DFT calculation for Ca and Ti containing molecules, DOI: 10.5281/zenodo.6607407), numerical simulations were provided for a set of molecules given isotopic enrichment by the laser-enhanced isotopically selective condensation method (J.-M. Zellweger et al. Isotopically selective condensation and infrared-laser-assisted gas-dynamic isotope separation. Physical Review Letters 52 (1984) 522-525. DOI: 10.1103/PhysRevLett.52.522). Based on preliminary computational investigations with density functional theory, also reported in Deliverable D10.5, it was concluded that calcium hexafluoroacetylacetonate (C10H2CaF12O4) is a promising molecule, offering opportunities to be separated by laser techniques in the gas phase. As this compound is commercially available, no in-depth investigation of its synthesis was required, as had been originally expected within PRISMAP. However, it is essential to verify the suitability of this compound for the laser application, by verifying experimentally the predicted spectrum of this molecule in the farand mid-infrared, as well as the predicted isotope shift, which shall eventually be exploited for the separation. The farand mid-infrared spectrum of calcium hexafluoroacetylacetonate (C10H2CaF12O4) molecules is characterised in the gas phase, using a free electron laser for excitation. The experimental apparatus has sufficient mass resolution to identify separately the signals from different stable Ca isotopes, allowing the recording of Ca-isotope specific infrared spectra. The main bottleneck, however, is the low intensity of peaks associated with any but Ca-40, given its large natural abundance (96.941%). Gas-phase infrared spectroscopy is employed here to experimentally investigate the vibrational modes of calcium hexafluoroacetylacetonate (C10H2CaF12O4) in the wide wavenumber range from 550 to 1700 cm-1. The measured spectrum agrees well with previous calculations, allowing a targeted laser excitation within PRISMAP at 490 cm-1, in order to resonantly excite a Ca isotope-sensitive vibration. A similar approach may also be followed for Ti-containing molecules, where we shall first identify a stable molecule, then perform the associated DFT calculations, and finally verify those with infrared light spectroscopy. 2. Medical Sc radionuclide production from isotopically enriched target materials Sc radionuclides have a high interest in nuclear medicine due to the possibility of producing “matched pair” radiopharmaceuticals for theranostics (DOI: 10.2967/jnumed.120.242941). They can be most effectively produced by activating Ti, Ca, or V target materials. Depending on the application, one must reach a certain level of radionuclidic purity of a specific Sc isotope. For application in nuclear medicine, long-lived, highenergy gamma-ray emitting contaminants must be avoided for unnecessary radiation dose and regulatory reasons. To reach higher radionuclidic purity, isotopically enriched target materials must be used. Several experimental campaigns and theoretical studies have been put in place for decades to determine the highest production yield (cross-section) for specific Sc isotopes such those of reasonably long half-life as Sc43 (T1/2 = 3.89 h), Sc-44g (T1/2 = 3.97 h), Sc-44m (T1/2 = 58.61 h), Sc-46 (T1/2 = 83.79 d), Sc-47 (T1/2 = 3.35 Deliverable D10.6 9 Based on the computational analysis, the features below 800 cm-1 should be sensitive to the Ca isotope. In particular, the mode was predicted at 480 cm-1, and to some extent, the mode at 560 cm-1. In this wavenumber range, modes are observed at 490, 530, 580, 660, 744, and 810 cm-1. Given the low intensity of the peak associated with 44Ca in mass spectra, assessing the isotopic shift experimentally was not possible with the sample composed of the natural Ca isotopic distribution. Further experiments with an isotopically enriched sample could potentially address this issue. Nevertheless, the good correspondence between the experimental and computational IR spectra allows us to assign the targeted excitation wavenumber to 490 cm-1. 5. Conclusions and outlook … Infrared multiple photon dissociation spectroscopy was used to record the farand mid-infrared spectrum of calcium hexafluoroacetylacetonate (C10H2CaF12O4) molecules in the gas phase. The frequencies of the measured spectrum measured here resemble well previously reported density functional theory calculations. While the use of a sample composed of the natural abundance of Ca does not allow to address experimentally the isotopic shift, the good agreement between theory and experiment reveals a targeted laser excitation at 490 cm-1. Following experiments, using an isotopically enriched sample could be applied to experimentally observe the isotopic shift. Moreover, it is noted that the current methodology can now be applied to any molecule that shall be identified as promising for PRISMAP, using either Ti or Ca. This confirms this commercially available calcium-based molecule allowed verification numerical simulations with experimental data for studying laser separation in the gas phase. This also helps guide the development of the necessary laser system, which should provide IR light at 490 cm-1, namely 20.4 μm. It should be observed, however, that the Ti analogue of the Ca compound shown in Figure 9 is probably not synthetically viable, so alternative structures will need to be explored in silico before synthesis. Four coordinate Ti complexes are highly unstable and only a few examples have been reported to date with very specialised ligands.