Artificial Foldamer‐Based Calcium Ion Carriers with High Ca²⁺/Mg²⁺ Selectivity Ratio

Comprehensive Summary Inspired by natural Ca 2+ channels, we design and synthesize a type of artificial Ca 2+ carriers using o ‐phenanthroline‐oxadiazole‐based foldamers. Through the incorporation of negative charges into cavity‐containing foldamers, highly selective calcium ion transmembrane transport can be achieved, leading to the identification of two highly efficient Ca 2+ carriers. Systematic investigation revealed a positive correlation between the number of negative charges on the foldamers and the foldamers‘ cation‐binding affinity. Furthermore, the size‐selective effect, achieved through precise matching between the foldamer cavity dimensions and Ca 2+ ion size, resulted in an unprecedented Ca 2+ /Mg 2+ selectivity ratio ( S Ca/Mg ), reaching record S Ca/Mg values greater than 100–the highest of all artificial Ca 2+ carriers reported to date. Moreover, artificial Ca 2+ carriers show high Ca 2+ transport activity (EC 50 = 190 nM). This simple and modular approach enables tailored design of divalent cation transporters, thus providing promising applications for artificial divalent cation transporters in the fields of biochemistry and material chemistry.