On the Design of Effective Water-Soluble Actinide-Masking Ligands Through Ligand Structure Modulation

Water-soluble actinide-masking ligands are fundamentally important for achieving efficient lanthanide/actinide separation and for the development of water-soluble f-block complexes for bioimaging and radiopharmaceutical applications. However, the underlying design principles remain largely elusive, particularly in achieving a fine balance between ligand water solubility and metal affinity/selectivity. In this study, it is demonstrated that for the well-established phenanthroline diimine ligand framework, topological modifications can preserve water solubility but introduce significant rotational energy barriers. These barriers, in turn, diminish both the metal-binding affinity and selectivity. Conversely, non-coordinating substituents play an unexpected role in modulating water solubility. Specifically, the incorporation of methylthio-flanking groups is found to significantly impair the ligand's aqueous solubility. A combination of solution- and solid-state coordination studies is employed to elucidate how structural modifications influence ligand-metal interactions. Additionally, DFT calculations provided molecular-level insights into the relationship between chemical structure, water solubility, and coordination behavior. This work offers valuable design guidelines for the development of hydrophilic ligands, with implications for selective f-block element separation and the formulation of stable, water-soluble f-block complexes.