Self‐Assembled Artificial Ion‐Channels toward Natural Selection of Functions

Abstract

Owing to their significant physiological functions, especially as selective relays for translocation of physiological relevant species through cellular membranes, natural ion channels play important role in the living organisms. During the last decades, the field of self‐assembled ion channels has been continuously developed. Convergent multidimensional self‐assembly strategies have been used for the synthesis of unimolecular channels or non‐covalent self‐organized channels, designed to mimic natural ion channel proteins and for which a rich array of interconverting or adaptive channel conductance states can be observed. In this review, we give an overview on the development of various self‐assembled artificial channels in a bottom‐up approach, especially their design, self‐assembly behaviour, transport activity in lipid bilayer membranes, mechanism of transport and comparison with natural ion channels. Finally, we discuss their applications, the potential challenges facing in this field as well as future development and perspectives.

Biomimetic Approach for Highly Selective Artificial Water Channels Based on Tubular Pillar[5]arene Dimers

“…The transport is regulated by proteins, converting the ion‐water interactions into ion‐selectivity filter ones [2] . Because of the high significance of the related processes, the design of synthetic unimolecular or self‐assembled channels with water‐ion [3] or ion‐ion [4, 5] selectivity have become areas of expanding interest. Very attractive strategies have been developed based on the self‐assembly, towards supramolecular capsules presenting conductance states in bilayer membranes.…”

A Synthetic Phospholipid Derivative Mediates Ion Transport Across Lipid Bilayers

“…Therefore, ion transport through membrane is actually a supramolecular function (Fyles, 2007 ). Inspired by the functional sophistication of ion transporters in nature, supramolecular chemists have created a variety of synthetic systems to replicate the transport functions by using small molecules and synthetic compounds (Kim and Sessler, 2015 ; Si et al, 2015 ; Chen et al, 2018a , b , 2020 ; Wu et al, 2018 ; Zhang et al, 2019 ; Zheng et al, 2020 ). It is of biological importance to build artificial ion transporters with desired properties, which will not only help to elucidate the possible mechanism by biological transporters, but also to provide early diagnosis and potential medical applications for the treatment of diseases caused by structural and functional abnormalities (such as “channelopathies”) (Zaydman et al, 2012 ).…”

“…In the design of synthetic transporters, most reported compounds have hydrophobic structures to facilitate the insertion of hydrophobic phospholipid bilayer membrane (Kim and Sessler, 2015 ; Si et al, 2015 ; Wu et al, 2018 ; Zheng et al, 2020 ). However, there are two obvious shortcomings in such a design, including the requirement of organic solvents to solute the compounds and the competitive self-precipitation in physiological solution before inserting in lipid membrane.…”

Switchable foldamer ion channels with antibacterial activity

“… 7 Of the wide range of artificial ion channels developed and studied, 8 several show either cation selectivity 9 or anion selectivity. 10 However, a significant challenge in the field is to “switch” any channel activity, 11 so that, like natural examples, activity can be controlled by external stimuli, such as light or chemical messengers. Closing channels by blocking the lumen with an added ligand is known, but examples of ligand-induced channel opening are less common.…”