Rare earth element selectivity controlled via hydrophobic guest residue in peptides derived from the EF-hand loop 1 of lanmodulin

The discovery of ligands with high selectivity for different rare earth elements (REEs) is still the most challenging problem in REE separation processes. In this work, seven new peptide ligands were designed using the EF-hand loop 1 of lanmodulin as a basis and by treating the isoleucine moiety found in the original sequence as a guest residue. The goal was to study the impact of substituting the guest residue with amino acids of varying hydrophobicity on the binding affinity and thermodynamics for various REEs. First, circular dichroism (CD) and molecular dynamics (MD) simulations were utilized to confirm the new sequences were capable of binding REEs. Later, the thermodynamic parameters (K d , ΔH, ΔS, and ΔG) of the interaction between the peptides with La(III), Ce(III), Pr(III) and Nd(III) ions in solution were determined using isothermal titration calorimetry (ITC) experiments. La(III), Ce(III) and Nd(III) ions were chosen due to their presence in phosphogypsum waste. A significant correlation was observed between the thermodynamic properties (∆H, ∆S and K d ) and the relative hydrophobicity of the guest residue in the designed peptide. The peptides exhibited varying binding affinities and selectivity for different REEs, with differences spanning up to 6.5 times for neighboring pairs. MD was used to further elucidate potential sources of enthalpy and entropy change. The relative hydrophobicity of the guest residues in the designed peptides, measured ∆H and ∆S were found to be correlated with simulation estimates of solvent-accessible surface area, the water in the hydration shell of the peptide, and the hydrogen bond decay of water molecules near the peptide, suggesting an intricate relation between interfacial water and the thermodynamic properties of complexation. Overall, the simulation results complemented the experimental data by revealing important molecular insights into the ion complexation process of lanmodulin-derived peptide sequences. • Seven new lanmodulin-derived peptide ligands were designed for REE binding. • Substitution of a guest residue modulated hydrophobicity and REE selectivity. • Circular dichroism (CD) and molecular dynamics (MD) simulations confirmed REE binding capability of all designed peptides. • Isothermal titration calorimetry (ITC) quantified thermodynamic properties K d , ΔH, ΔS, and ΔG for La(III), Ce(III), Pr(III), and Nd(III). • Relative hydrophobicity correlated with thermodynamic properties.