Enforced folding of unnatural oligomers: Creating hollow helices with nanosized pores

This article reviews the progress made during the last several years on developing folding helical oligomers consisting of aromatic residues based on a backbone-rigidification strategy. In this approach, rigid, planar, aromatic residues are linked by planar linkers such as amide and urea functionalities. Folding into helical conformations is realized based on the incorporation of localized intramolecular hydrogen bonds that limit the rotational freedom of the backbones, and through the introduction of backbone curvature by linking the aromatic residues in a nonlinear fashion. As a result, the corresponding oligomers are forced to adopt well-defined helical conformations containing interior cavities. Changing the backbone curvature leads to the tuning of the cavity sizes. Such enforced folding based on a "tying up" leads to stable helical backbones that are independent of side chain substitution, which offers a variety of robust helical scaffolds for presenting functional groups. The pore-containing helices combine the feature of secondary and tertiary structures, a feature seen in few other natural or unnatural folding systems. Such an enforced folding approach should provide a simple, predictable strategy for developing a new class of nanoporous structures with predictable dimensions.