Aromatic Oligoamide β‑Sheet Foldamers

A rational
approach for the construction of multi-stranded artificial
β-sheets based not on hydrogen bonding, but rather on π–π
aromatic stacking, is presented. Using 4,6-dinitro-1,3-phenylenediamine
units, rigid turns were designed that allow face-to-face π–π
interactions between appended linear aromatic segments to be strong
enough for folding in an organic solvent, but weak enough to prevent
aggregation and precipitation. Solution and solid-state studies on
a series of turn units showed that the desired degree of rigidity,
resulting from hindered bond rotation, could be fine-tuned by the
inclusion of additional methyl substituents on the aromatic rings.
The high degree of preorganization afforded by these qualities further
allowed the facile preparation of macrocyclic sheet structures from
their noncyclic precursors. These macrocycles were shown to have slow
internal dynamics and defined conformational preferences. Using this
background, three- and five-stranded artificial β-sheets were
synthesized and their folded conformations extensively characterized
in solution by NMR. The solid-state structures of the three- and five-stranded
sheets were also elucidated in the solid state by X-ray crystallography
and confirmed intramolecular π–π aromatic stacking.