Artificial Chloride-Selective Channel: Shape and Function Mimic of the ClC Channel Selective Pore

Abstract

An artificial channel molecule 1 that mimics the shape and function of the ClC channel selective pore was described. To facilitate the transport of chloride along a unimolecular pathway, anion−π interactions were introduced as the noncovalent driving force. The hourglass-like shape of 1 was constructed with 1,3-alternate tetraoxacalix­[2]­arene­[2]­triazine as the narrowest (central) unit. Two diglycolamine-linked imide arms were tethered as the extending part, and phenylalanine moieties were fixed as the terminal anchoring groups. The ion transport activity was examined by a combination of vesicle and planar bilayer conductance techniques (BLM). The fluorescence analysis on the vesicle indicated that 1 is an efficient chloride transporter with high activity (EC50 = 1.50 μM; 1/lipid = 1:89). The ion channel characteristics were confirmed by BLM measurements, showing an average conductance of 20.8 ± 1.0 pS in symmetric KCl solutions (cis/trans = 1.0 M/1.0 M). Anion/cation selectivity with a permeability ratio P Cl –/P K + = 1.90 in an asymmetric KCl solution (cis/trans = 1.0 M/0.25 M) and anion/anion selectivity with P Cl –/P Br – = 22.83 in a KCl/KBr solution (cis/trans = 1.0 M KCl/1.0 M KBr) were demonstrated.

Super-assembly of freestanding graphene oxide-aramid fiber membrane with T-mode subnanochannels for sensitive ion transport

“…52 According to the Goldman–Hodgkin–Katz equation, the permeability ratio of chloride ion to metal ion was calculated to be 158 and 18 for KCl and MgCl 2 , respectively. 53 The higher K + /Cl − ratio confirms that the permselectivity of KCl is superior than MgCl 2 for the GO/ANF/GO composite membrane. The I – V curve of the GO/ANF/GO composite membrane with a 10 4 -fold concentration gradient (10 −5 /0.1, KCl) is shown in Fig.…”

Supramolecular chemistry in lipid bilayer membranes

“…98 In 2020, Wang and co-workers developed an artificial chloride selective channel inspired by the hourglass shape of the natural CLC channel (Figure 11A). 99 The electron deficient triazine-based macrocycle appended to four electron deficient imides leads to high anion transport activity via anion-π interactions, and organises the system into the "hour glass" conformation. The high Cl − > Br − selectivity was attributed to the narrow macrocyclic cavity preferring the smaller and more strongly bound Cl − , leading to exclusion of incoming Br − .…”

“…102 An impressive example includes a multi-block amphiphile (Figure 11B), which inserts itself into the bilayer in a controlled orientation due to its amphiphilic nature; allowing gating of ion transport activity with both agonistic and antagonistic ligands. 100 The charged phosphate groups function as a binding site for aromatic amines and ensure high dispersion in aqueous Figure 11 Unimolecular channels A. CLC chloride channel with key helical domains (PDB: 1KPL) and CLC mimic 99 ; B. Multiblock amphiphile by Kinbara with anisotripic ligand response 100 C. Gramicidin-modified pillararenes by Chen 103 D. Rigid rod ion channels reported by Zhu and co-workers. 104 environments.…”

Crystal Packing‐Guided Construction of Hetero‐Oligomeric Peptidic Ensembles as Synthetic 3‐in‐1 Transporters

“…Nevertheless, over the past four decades of intensive research since the first report on the synthetic transporter in 1982, [11] study on the synthetic membrane transporters has overwhelmingly focused on transport of inorganic cations [12–37] or anions, [38–60] with much less on molecular species such as water [61–71] and glucose [72] . Specific to synthetic amino acid transporters, we are aware of only two artificial transporter systems based on a pillar[5]arene derivative by Hou in 2013 [73] or dynamic covalent bonds by Gale in 2015 [74] …”