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

Abstract

Inspired by natural Ca²⁺ channels, we design and synthesize a type of artificial Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ ion size, resulted in an unprecedented Ca²⁺/Mg²⁺ selectivity ratio (S_Ca/Mg), reaching record S_Ca/Mg values greater than 100–the highest of all artificial Ca²⁺ carriers reported to date. Moreover, artificial Ca²⁺ carriers show high Ca²⁺ transport activity (EC₅₀ = 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.

Keywords

Ion transport / Foldamer / Ion selectivity / Ionophores / Calcium / Molecular recognition / Self-assembly / Supramolecular chemistry

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