Cyclodextrin ion channels

Abstract

Seventeen derivatives of α- and β-cyclodextrins were prepared from the cyclodextrin per-6-azide by “click” cyclization with terminal alkynes. Sixteen of these “half-channel” compounds showed significant activity as ion channels in planar bilayer members as assessed by the voltage-clamp technique. Activity ranged from persistent square-top openings to highly erratic conductance; mixed behaviours were evident in virtually all data recorded. Some of the erratic behaviours were shown to follow an apparent power-law distribution of open duration times. The activities observed for the suite were summarized using a model-free activity grid method which displays conductance, duration, and opening behaviour. The overall activity shows the clustering of conductance–duration indicating that activity arises from system properties rather that solely as a property of the compound. The activity grids also support an analysis of structure–activity relationships as they apply to the global behaviour of the compounds and reveal the complexity of a single structure change in controlling the distribution of concurrent conductance behaviours. Transient blockage of channel activity by the hydrophobic guest of the cyclodextrin (1-adamantyl carboxylate) is consistent with the formation of an end-to-end dimer channel among several other competing and interconverting structures.