Metal ion separations are critical to numerous fields, including nuclear medicine, waste recycling, space exploration, and fundamental research. Nonetheless, operational conditions and performance are limited, imposing compromises between recovery, purity, and cost. Siderophore-inspired ligands show unprecedented charge-based selectivity and compatibility with harsh industry conditions, affording excellent separation efficiency, robustness and process control. Here, we successfully demonstrate a general separation strategy on three distinct systems, for Ac, Pu, and Bk purification. Separation factors (SF) obtained with model compound 3,4,3-LI(1,2-HOPO) are orders of magnitude higher than with any other ligand currently employed: 106 between Ac and relevant metal impurities, and over 108 for redox-free Pu purification against uranyl ions and trivalent actinides or fission products. Finally, a one-step separation method (SF > 3 × 106 and radiopurity > 99.999%) enables the isolation of Bk from adjacent actinides and fission products. The proposed approach offers a paradigm change for the production of strategic elements.