Mimicking the Shape and Function of the ClC Chloride Channel Selective Pore by Combining a Molecular Hourglass Shape with Anion–π Interactions

ClC is the main family of natural chloride channel proteins that transport Cl− across the cell membrane with high selectivity. The chloride transport and selectivity are determined by the hourglass‐shaped pore and the filter located in the central and narrow region of the pore. Artificial unimolecular channel that mimics both the shape and function of the ClC selective pore is attractive, because it could provide simple molecular model to probe the intriguing mechanism and structure‐function relevance of ClC. Here we elaborated upon the concept of molecular hourglass plus anion–π interactions for this purpose. The concept was validated by experimental results of molecular hourglasses using shape‐persistent 1,3‐alternate tetraoxacalix[2]arene[2]triazine as the central macrocyclic skeleton to control the conductance and selectivity, and anion–π interactions as the driving force to facilitate the chloride dehydration and movement along the channel. The concept of combining molecular hourglass with anion–π interactions for mimicking the shape and function of the ClC chloride channel selective pore is presented. High and regulatable chloride transport conductance and selectivity that replicate the properties demonstrated by ClC is achieved through modifying the constituent components of the molecular hourglass.