Highly selective and efficient processes are deeply needed for producing high-purity isotopes for research or medical applications and for treating the radioactive waste. Herein, we describe a new approach for separating metal ions based-on bio-inspired synthetic chelators. Versatile liquid-liquid extraction processes were developed for the separation of a variety of strategic elements. These new chelators exhibit a much higher selectivity than other ligands used for extraction such as the carboxylic acids. Separation factors (SF’s) of about 100 were obtained for americium(III) and gadolinium(III). SF’s of 1,000 to 10,000 were obtained for berkelium and adjacent actinides (Am, Cm, Cf, Es). In a single step, SF’s of 30,000 to 300,000 for plutonium and lanthanide(III) ions can be obtained. Separation factors as high as 1,000,000 can also be reached for actinium against other f-elements. The results support the development of practical, versatile, and highly selective systems based on these bio-inspired chelators.