Twisted Macrocycles with Folded <i>ortho</i>-Phenylene Subunits

Many foldamers, oligomers that adopt
well-defined secondary structures,
are now known, including many exhibiting functional behavior. However,
examples of foldamer subunits within larger architectures remain rare,
despite the importance of higher-order structure in biomacromolecules.
Here, we investigate the dynamic covalent assembly of short o-phenylenes, a simple class of aromatic foldamers, into
twisted macrocycles. o-Phenylene tetramers have been
combined with rod-shaped p-phenylene-, tolane-, and
diphenylbutadiyene-based linkers using imine formation. Macrocyclization
proceeds efficiently, inducing folding of the o-phenylenes.
The resulting [3 + 3] macrocycles (three o-phenylenes
and three linkers) are shape-persistent, triangular structures with
twisted cores and internal diameters up to approximately 2 nm. The
homochiral D3-symmetric and heterochiral C2-symmetric conformers can be distinguished
by NMR spectroscopy. Analysis of the conformational distribution for
the p-phenylene-linked macrocycle suggests that the o-phenylene units are largely decoupled, with the less-symmetrical
configuration therefore entropically favored. Conformational dynamics
were assessed by variable-temperature NMR spectroscopy. Confinement
within the macrocyclic architecture slows the inversion of the o-phenylene moieties.