Supramolecular Barrel‐Rosette Ion Channel Based on 3,5‐Diaminobenzoic Acid for Cation‐Anion Symport

The structural tropology and functions of natural cation‐anion symporting channels have been continuously investigated due to their crucial role in regulating various physiological functions. To understand the physiological functions of the natural symporter channels, it is vital to develop small‐molecule‐based biomimicking systems that can provide mechanistic insights into the ion‐binding sites and the ion‐translocation pathways. Herein, we report a series of bis((R)‐(−)‐mandelic acid)‐linked 3,5‐diaminobenzoic acid based self‐assembled ion channels with distinctive ion transport ability. Ion transport experiment across the lipid bilayer membrane revealed that compound 1 b exhibits the highest transport activity among the series, and it has interesting selective co‐transporting functions, i.e., facilitates K+/ClO4− symport. Electrophysiology experiments confirmed the formation of supramolecular ion channels with an average diameter of 6.2±1 Å and single channel conductance of 57.3±1.9 pS. Selectivity studies of channel 1 b in a bilayer lipid membrane demonstrated a permeability ratio of PCl-/PK+=0.053±0.02 ${{P}_{{Cl}^{-}}/{P}_{{K}^{+}}=0.053\pm 0.02}$ , PClO4-/PCl-=2.1±0.5 ${{P}_{{ClO}_{4}^{-}}/{P}_{{Cl}^{-}}=2.1\pm 0.5}$ , and PK+/PNa+=1.5±1, ${{P}_{{K}^{+}}/{P}_{{Na}^{+}}=1.5\pm 1,}$ indicating the higher selectivity of the channel towards KClO4 over KCl salt. A hexameric assembly of a trimeric rosette of 1 b was subjected to molecular dynamics simulations with different salts to understand the supramolecular channel formation and ion selectivity pattern. Bis((R)‐(−)‐mandelic acid)‐linked 3,5‐diaminobenzoic acid‐based supramolecular barrel‐rosette ion channels have been synthesized that possess a distinctive combination of hydrogen‐bond forming and lone‐pair donating groups within the channel cavity. This allows them to function as cation‐anion symporters, with profound selectivity towards KClO4.