Towards New Spectroscopic Tools for Detection of Bonding Properties in Radiopharmaceuticals: Application on La Used as a Homolog of Ac

In recent years the use of radiopharmaceuticals based on alpha-particle emitting radionuclides has seen a considerable growth. In pre-clinical research and first clinical trials targeted alpha therapy has shown great potential. However, there are still many challenges in this field, one being the need for tight chelating of the aforementioned alpha-emitting radionuclides and their daughters. We aim to understand relations between bonding properties and bond stability of such compounds.
The recently evolved high-energy resolution X-ray absorption near edge structure (HR-XANES) spectroscopy has been proven a valuable tool for the study of the electronic structure of actinides.1-2 Here we employ it first to study the bonding properties of La, a homolog of Ac, with different ligands in discussion as nuclide binding site in radiopharmaceuticals for targeted alpha treatment.
La3+(aq), La3+ in buffer media, La-DOTA, La-MACROPA and La-PSMA, have been prepared and characterized. We measured La L2-edge HR-XANES spectra at the Synchrotron Laboratory for Environmental Studies (SUL-X) beamline and La L3-edge extended X-ray absorption fine structure spectroscopa (EXAFS) at the INE-Beamline at the KIT Light Source. ... mehrAdditionally, density functional theory (DFT) and ab initio fine difference method near-edge structure (FDMNES) calculations were used to compute the spectra. Bonding interactions were evaluated using natural orbitals for chemical valence (NOCV) and quantum theory of atoms in molecules (QTAIM) which describes the topology (i.e., shape and magnitude) of the electron density between two bonded atoms.
Several tools (spectroscopic and theoretical) to determine the covalency of the La-ligand bond were developed. One example of this measure can be the comparison of position and shape of the pre- and main absorption edges. EXAFS and HR-XANES analysis gave insights into the coordination environment. With QTAIM bond analysis the covalent from the ionic part of the bonding was differentiated. Combined these results are the first steps towards developing new spectroscopic tools that will help understand the electronic structure and the bonding and will potentially help designing new chelating ligands for use in radiopharmaceuticals for targeted alpha therapy.
1. Pruessmann, T.; Nagel, P.; Simonelli, L.; Batchelor, D.; Gordon, R.; Schimmelpfennig, B.; Trumm, M.; Vitova, T., Opportunities and challenges of applying advanced X-ray spectroscopy to actinide and lanthanide N-donor ligand systems. J Synchrotron Radiat 2022, 29, 53-66.
2. Vitova, T.; Roesky, P. W.; Dehnen, S., Open questions on bonding involving lanthanide atoms. Commun Chem 2022, 5 (1).