Mechanisms of chiral induction in foldamers

Foldamers, oligomers that adopt well-defined conformations, represent an efficient strategy toward nanoscale structural complexity. While most foldamers fold into (chiral) helices, many abiotic foldamers are built from achiral repeat units. They therefore do not have a preferred twist sense. The handedness can, however, be controlled by attaching groups with chirality centers to the foldamer backbone. This process allows the chiral information from readily available feedstocks 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 the helicity of the foldamer to which they are attached. We highlight examples of aromatic oligoamides, oligohydrazides, oligoindoles, oligo(ortho-phenylenes), 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 in space relative to its direct point of attachment to the foldamer. We then consider long-range interactions between the controller group and more-distant parts of the oligomer, typically one turn farther along the helix. Together, these interactions allow the twist sense to be predicted (or rationalized). Understanding these mechanisms should facilitate the design of systems with dynamic control over helicity.