Artificial K⁺Channels Formed by Pillararene‐Cyclodextrin Hybrid Molecules: Tuning Cation Selectivity and Generating Membrane Potential

Abstract

Ac lass of artificial K + channels formed by pillararene-cyclodextrin hybrid molecules have been designed and synthesized.T hese channels efficiently inserted into lipid bilayers and displayed high selectivity for K + over Na + in fluorescence and electrophysiological experiments.The cation transport selectivity of the artificial channels is tunable by varying the length of the linkers between pillararene and cyclodexrin. The shortest channel showed specific transmembrane transport preference for K + over all alkali metal ions (selective sequence:K + > Cs + > Rb + > Na + > Li + ), and is rarely observed for artificial K + channels.T he high selectivity of this artificial channel for K + over Na + ensures specific transmembrane translocation of K + ,a nd generated stable membrane potential across lipid bilayers.

Multifunctional Pillar[n]arene-Based Smart Nanomaterials

“…Moreover, the rigid pillar backbone of PAs and its assembly in tubular structures have inspired its implementation in the development of artificial transmembrane channels for ion, water, and protein transport . Generally, PAs are functionalized with other macrocycles, peptide chains or other moieties, via click reactions or cabodiimide cross-linking to study the overall effect on the performance of the synthetic ion channels. − …”

“…It was observed that the shortest the linker, the higher the efficiency of K + mobility and K + selectivity, due to restricted flexibility (Figure d). In addition, the amphiphilic nature of this system (hydrophobic pillar[5]­arene and hydrophilic α-CD) allowed its incorporation into the lipid bilayer displaying high stability …”

Unimolecular Helix-Based Transmembrane Nanochannel with a Smallest Luminal Cavity of 1 Å Expressing High Proton Selectivity and Transport Activity

“…As shown in Figure d, after adding 16mer (5 μM) to the extravesicular solution of LUVs, the fluorescence intensity of the extravesicular Safranin O dye (200 nM) increased obviously, indicating that a negative potential was generated from the outside to the inside of the membranes. It can be seen that the fluorescent emission reached a maximum plateau at 100–120 s and then gradually decreased along with depolarization process, which is a common phenomenon in highly selective ion channels . The Safranin O assay has convincingly confirmed the monodirectional movement of protons through the helix-based channel.…”

“…It can be seen that the fluorescent emission reached a maximum plateau at 100−120 s and then gradually decreased along with depolarization process, which is a common phenomenon in highly selective ion channels. 43 The Safranin O assay has convincingly confirmed the monodirectional movement of protons through the helix-based channel. Furthermore, the membrane integrity and stability of the EYPC-based LUVs were further assessed by the 5(6)-CF leakage experiments.…”

Ionophore constructed from non-covalent assembly of a G-quadruplex and liponucleoside transports K+-ion across biological membranes

“…Unlike natural ion channels, artificial ionophores show low selectivity and lack stimuli-responsive behavior. Therefore, developing artificial ionophores with preference for a particular ion is an attractive area of research [39][40][41][42] .…”