Increasing the size of an aromatic Helical Foldamer cavity by strand intercalation

Abstract

The postsynthetic modulation of capsules based on helical aromatic oligoamide foldamers would be a powerful approach for controlling their receptor properties without altering the initial monomer sequences. With the goal of developing a method to increase the size of a cavity within a helix, a single-helical foldamer capsule was synthesized with a wide-diameter central segment that was designed to intercalate with a second shorter helical strand. Despite the formation of stable double-helical homodimers (Kdim> 107m-1) by the shorter strand, when it was mixed with the single-helical capsule sequence, a cross-hybridized double helix was formed with Ka>105m-1. This strategy makes it possible to direct the formation of double-helical heterodimers. On the basis of solution-and solid-state structural data, this intercalation resulted in an increase in the central-cavity size to give a new interior volume of approximately 150 Å 3.