Combinatorial Evolution of Fast-Conducting Highly Selective K+-Channels via Modularly Tunable Directional Assembly of Crown Ethers

We describe here a modularly tunable molecular strategy for construction and combinatorial optimization of highly efficient K+-selective channels. In our strategy, a highly robust supramolecular H-bonded 1D ensemble was used to order the appended crown ethers in such a way that they roughly stack on top of each other to form a channel for facilitated ion transport across the membrane. Among 15 channels that all prefer K+ over Na+ ions, channel molecule 5F8 shows the most pronounced optimum for K+ while disfavoring all other biologically important cations (e.g., Na+, Ca2+ and Mg2+). With a K+/Na+ selectivity of 9.8 and an EC50 value of 6.2 μM for K+ ion, 5F8 is clearly among the best synthetic potassium channels developed over the past decades.