Mechanisms of Chiral Induction to Foldamer Backbones

Foldamers, oligomers that adopt well-defined conformations, represent an efficient strategy toward nanoscale structural complexity. While most foldamers fold into helices, many abiotic foldamers are built from achiral repeat units and therefore do not have a preferred twist sense. Their handedness can, however, be controlled by attaching groups with chirality centers to the foldamer backbone. This process allows chiral information from readily available compounds to be amplified into larger-scale structural asymmetry and translated into functional behavior. This review describes mechanisms whereby the point chirality of chiral "controller" groups directs foldamer twist sense. We highlight examples of aromatic oligoamides, oligohydrazides, oligoindoles, oligo(ortho-phenylenes), oligooxymethylenes, and oligo(aminoisobutyric acids), examining cases where the controller groups are attached at either the helices' termini or sides. Our emphasis is on applying intuitive concepts from conformational analysis and, where appropriate, computational modeling of small substructures. In each case, we consider first short-range interactions that orient the controller group relative to its direct point of attachment to the foldamer, and then its long-range interactions with more-distant parts of the oligomer. Together, these interactions allow the twist sense to be predicted (or at least rationalized). Understanding these mechanisms should facilitate the design of systems with dynamic control over helicity.