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

Abstract

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, Ca and Mg). With a K/Na selectivity of 9.8 and an EC value of 6.2 μM for K ion, 5F8 is clearly among the best synthetic potassium channels developed over the past decades.

Pyridine/Oxadiazole‐Based Helical Foldamer Ion Channels with Exceptionally High K+/Na+ Selectivity

“…Current traces plotted against voltages yielded both the potassium conduction rate (γ K+ ) and the ion selectivity ratio ( P K+ / P Na+ ) for these two channels (Figures c,d). The determined conductance values of 16.2±0.5 pS for P 23 and 24.1±0.2 pS for P 27 , which are comparable to 23.2±0.4 pS obtained for the gramicidin A channel, confirm the high activity of P n ‐mediated transport of K + ions. Significantly, on the basis of the determined reverse potential values ( ϵ rev , Figures c,d; Figures S11 and S15) and ϵ rev = RT / F × ln( P K +/ P Na + ) (the universal gas constant R =8.314 J K −1 mol −1 , T =300 K, Faraday's constant F =96 485 C mol −1 , and P is the ion permeability), K +/ Na + selectivities for P 23 and P 27 were calculated to be 16.3 and 12.6, respectively, which are exceptionally high among synthetic ion channels …”

Polyhydrazide‐Based Organic Nanotubes as Efficient and Selective Artificial Iodide Channels

“…We evaluated the ability of these polymers to plug into a lipid membrane and to transport ions across the membrane using a fluorescence assay (Figure a), which employs the pH‐sensitive fluorescent dye HPTS (8‐hydroxy‐1,3,6‐pyrenetrisulfonate) trapped inside egg yolk phosphatidylcholine (EYPC) based, large unilamellar vesicles (LUVs) . In this assay, a pH gradient of 7 to 8 was applied across the vesicles, and ion‐transport activities were monitored by the incremental changes in the HPTS fluorescence ( λ ex =450 nm, λ em =510 nm) over a 300 second period with that induced by Triton X‐100 (added at t =300 s) set as 100 % (Figure b).…”

Driving Smart Molecular Systems by Artificial Molecular Machines

“…Passive transport exploits the concentration gradient (high–low), whereas active transport acts in the reverse direction (low–high) and is facilitated by ion transporters, as exemplified by ATP hydrolysis and bimolecular machines. Inspired by these transport processes and their potential therapeutic applications, researchers constructed various artificial transmembrane ion transport systems with control possibility to mimic biological transport processes and functions . Qu and coworkers constructed a [2]rotaxane‐based molecular shuttle for the transmembrane transport of potassium ions.…”