Multiple Conductance States in Artificial Unimolecular Channels

Since the 1980s, the patch-clamp technique has revealed subconductance states (substates) in natural ion channels in addition to the traditional closed and fully open states. While subconductance states offer critical insights into the structure and function of ion channels, the structural basis underlying this behavior remains unclear. Artificial ion channels can serve as simplified molecular models to establish structure-function relationships; however, replicating subconductance behavior is extremely challenging. Here, we present a concept for a conformationally self-tuning macrocyclic skeleton designed to observe and modulate subconductance states in artificial channels. This concept was experimentally validated using oxacalix[2]arene[2]triazine-based molecular funnels.