Directing Foldamer Self-Assembly with a Cyclopropanoyl Cap

Abstract

The rational design of self-assembling organic materials is extremely challenging due to the difficulty in precisely predicting solid-state architectures from first principles, especially if synthons are conformationally flexible. A tractable model system to study self-assembly was constructed by appending cyclopropanoyl caps to the N termini of helical α/β-peptide foldamers, designed to form both N−H⋅⋅⋅O and C α −H⋅⋅⋅O hydrogen bonds, which then rapidly self-assembled to form foldectures (foldamer architectures). Through a combined analytical and computational investigation, cyclopropanoyl capping was observed to markedly enhance self-assembly in recalcitrant substrates and direct the formation of a single intermolecular N−H⋅⋅⋅O/C α −H⋅⋅⋅O bonding motif in single crystals, regardless of peptide sequence or foldamer conformation. In contrast to previous studies, foldamer constituents of single crystals and foldectures assumed different secondary structures and different molecular packing modes, despite a conserved N−H⋅⋅⋅O/C α −H⋅⋅⋅O bonding motif. DFT calculations validated the experimental results by showing that the N−H⋅⋅⋅O/C α −H⋅⋅⋅O interaction created by the cap was sufficiently attractive to influence self-assembly. This versatile strategy to harness secondary noncovalent interactions in the rational design of self-assembling organic materials will allow for the exploration of new substrates and speed up the development of novel applications within this increasingly important class of materials. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.