Encapsulation versus Self-Aggregation toward Highly Selective Artificial K+ Channels

Natural ion-channel proteins allow ion transport across cell membranes at rates very close to those for ionic diffusion in water. Among them, natural KcsA K+ channels present high transport rates and total selectivity for K+ cations, rejecting all other cations. Most of the reported artificial ion channels cannot reach this type of activity because of their low selectivity. Several synthetic channels have been designed to mimic the natural KcSA channels, but those presenting an important K+/Na+ selectivity are limited. High-selectivity issues are determinant for the performance of natural protein channels, but they have been not considered as determinant in controlling the transport activity of the artificial ion channels. This Account discusses the last developments of artificial supramolecular carriers or channels that selectively transport K+ cations against other cations. Mimicking the complex structures of protein channels is an important research area. These studies are related to such adaptive biomimetic systems that can self-select their functions, with a specific emphasis on artificial superstructures enabling K+ transport like in the natural ones. Alternatively, it is more than interesting to synthetically construct only the active key structures of protein filters or gates that give the chemical selectivity or lead us to describe their dynamic role in the ion pumping and translocation along the channel. Several self-assembled macrocyclic channels are presented here. The macrocyclic binding sites may selectively encapsulate the K+ cations or form aggregated H-bonded central pores of self-assembled macrocycles that coordinate the K+ cations as hydrating water molecules in aqueous solution, compensating for the energetic cost of cation dehydration. These macrocyclic channels are responsive in the presence of K+ cations, even when a large excess of Na+ is present. From the mechanistic point of view, these systems express a synergistic dynamic feature: addition of K+ cations drives the selection and emergence of specific ion channels that selectively conduct the K+ cations that promoted the formation of channel superstructures in the first place. These highly permeable and K+-selective artificial channels may be considered as simple primitive biomimetic alternatives of natural KcsA channels that may find interesting applications in chemical separations, selective sensing, and biomedical materials.