Molecular Tetrahedrons as Selective and Efficient Ion Transporters via a Two-Station Swing-Relay Mechanism (vol 2, pg 2269, 2020)

The traditional approach to utilizing an ion-relay mechanism for ion transport requires three or more ion-relay stations. Herein, we describe a novel strategy, incorporating a swing action to realize a minimal ion-relay mechanism via only two relay stations. This swing-relay mechanism was achieved using a class of crown ether-appended, long-armed molecular tetrahedrons (MTs). These MTs comprise ion-relaying crown units attached to a rigid tetrahedral core via flexible alkyl linkers, which act as the mobile arms and endow the crown units with great mobility to swing. Driven by the ionic concentration gradient and supported by the mobile arms, two crown units located in the membrane's opposite hydrophilic regions swing toward each other to complete a single ion-relay step in the center of the membrane to enable fast ion conduction across. Generally, 18-crown-6-containing MT6s exhibited higher activities and better K+/Na+ selectivities than 15-crown-5-containing MT5s, with the most active MT6-C10 displaying an EC50 (K+) of 0.9 mu M (i.e., 0.9 mol % relative to lipid) and the most selective MT6-C4 showing K+/Na(+ )selectively of 6.3. Finally, five control MTs were rationally designed to establish the action of the novel unimolecular two-station swing-relay as an efficient yet unprecedented mechanism of synthetic ion transporters.