**Selective Proton-Mediated Transport by Electrogenic K** +**-Binding Macrocycles**

### **Yu-Hao Li 1, Shao-Ping Zheng 1, Dawei Wang 1 and Mihail Barboiu 1,2,\***


Received: 13 December 2019; Accepted: 16 January 2020; Published: 20 January 2020

**Abstract:** Synthetic K<sup>+</sup>-binding macrocycles have potential as therapeutic agents for diseases associated with KcsA K<sup>+</sup> channel dysfunction. We recently discovered that artificial self-assembled *n*-alkyl-benzoureido-15-crown-5-ether form selective ion-channels for K<sup>+</sup> cations, which are highly preferred to Na<sup>+</sup> cations. Here, we describe an impressive selective activation of the K<sup>+</sup> transport via electrogenic macrocycles, stimulated by the addition of the carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP) proton carrier. The transport performances show that both the position of branching or the size of appended alkyl arms favor high transport activity and selectivity SK+/Na<sup>+</sup> up to 48.8, one of the best values reported up to now. Our study demonstrates that high K+/Na<sup>+</sup> selectivity obtained with natural KcsA K<sup>+</sup> channels is achievable using simpler artificial macrocycles displaying constitutional functions.

**Keywords:** ion-channels; crown-ethers; bilayer membranes; self-assembly; supramolecular chemistry
