Controlling Dipole Orientation through Curvature: Aromatic Foldamer Bent β‑Sheets and Helix–Sheet–Helix Architectures

The
helix, turn, and β-strand motifs of biopolymer folded
structures have been found to prevail also in non-natural backbones.
In contrast, foldamers with aryl rings in their main chains possess
distinct conformations that may give access to folded objects beyond
the reach of peptidic and nucleotidic backbones. In search of such
original architectures, we have explored the effect of bending aromatic
amide β-sheets using building blocks that impart curvature.
Cyclic and multiturn noncyclic sequences were synthesized, and their
structures were characterized in solution and in the solid state.
Stable bent-sheet conformations were shown to prevail in chlorinated
solvents. In these structures, folding overcomes intramolecular electrostatic
repulsions and forces local dipoles in each layer of the stacked strands
to align in a parallel fashion. Sequences having helical segments
flanking a central bent aromatic β-sheet were then synthesized
and shown to form well-defined helix–turn–helix architectures
in which helical and sheet subcomponents conserve their respective
integrity. These objects have a unique basket shape; they possess
a cavity the depth and width of which reflects the curvature of the
β-sheet segment. They can be compared to previously described
helical closed-shell receptors in which a window has been open, thus
providing a means to control guest binding and release pathways and
kinetics. As a proof of concept, guest binding to one of the helix–sheet–helix
structures is indeed found to be fast on the NMR time scale while
it is generally slow in the case of helical capsules.