Determination of structures and binding energies of europium(III) complexes bound to biologically relevant anions

Anion sensing is a crucial area of research with applications in medical diagnostics, environmental monitoring and industrial analysis. Lanthanide complexes are actively studied for these purposes, particularly in biological media, as their positively charged central cations can provide strong electrostatic interactions with the respective analytes and because their unique photophysical properties allow for efficient detection. Within this work, we investigate the suitability of various computational methods to determine the geometries of europium(III) complexes and their binding energies to anions of biological relevance, putting special emphasis on the influence of conformational flexibility. We find that the composite r²SCAN-3c method produces accurate geometries at a low computational cost and that numerical stability as well as computational efficiency are increased when using a Y atom as proxy for Eu. We highlight the importance of conformational flexibility, necessitating an appropriate conformer search algorithm. Finally, when studying binding energies in host-guest complexes, we find that, despite investigating a range of methodological influences, we are unable to find a computational protocol that achieves even semi-quantitative accuracy. In summary, this work provides a solid starting point for future investigations on luminescent lanthanide(III) complexes and their anion sensing properties while also illustrating the open challenges.