Supramolecular Assembly of Lanthanide-Binding Tag Peptides for Aqueous Separation of Rare Earth Elements

Selective and eco-friendly separation and purification methods for rare earth elements (REEs) are necessary to meet the increasing demand for these valuable metals, which are extensively used in modern electronics and clean energy technologies. Mining feedstocks consist of REE mixtures as stable trivalent cations (Ln³⁺) that are difficult to separate due to their identical charge and similar size. Lanthanide-binding tags (LBTs), peptide chelates that coordinate Ln³⁺ in binding pockets, show promise as selective, high-affinity extractants. We demonstrate that the LBT variant LBTLLA^5–, designed for high selectivity for Tb³⁺, is an effective extractant, forming complexes with REEs in solution that subsequently organize into self-assembling structures rich in Ln³⁺. These structures condense into aggregates that can be separated, enabling an efficient, all-aqueous, eco-friendly separation process. The self-assembled structures are studied using dynamic light scattering, ζ-potential measurements, transmission electron microscopy, anomalous small-angle X-ray scattering, inductively coupled plasma optical emission spectroscopy, and ultraviolet–visible absorption spectroscopy, which confirm LBTLLA^5– peptide-REE ion binding and the further assembly of micron-scale structures rich in REEs. Molecular dynamics simulations reveal the interactions promoting aggregation as well as the integrity of the binding pocket upon self-assembly. We find that LBTLLA^5–:Ln³⁺ complexes recruit excess cations within the macrostructures, and we demonstrate that aggregation and selective separation can be controlled by manipulating the metal-peptide ratio in solution. Furthermore, we demonstrate separation from equimolar mixtures of REE pairs Tb³⁺-Lu³⁺ and Tb³⁺-La³⁺, supporting the application of LBT peptides as a platform for the selective separation of REEs.