Amyloid-like behavior in abiotic, amphiphilic foldamers.

Previously, we reported an abiotic amphiphilic foldamer that, upon heating, undergoes an irreversible conformational change to a highly aggregated state (Nguyen, J.Q.; Iverson, B.L. J. Am. Chem. Soc. 1999, 121, 2639-2640.). Herein, we extend this work through the study of a series of structurally related amphiphilic foldamers and present a more refined model of their conformational switching behavior. Prior to heating, all foldamers of the series exhibited spectral characteristics consistent with folding in the pleated, stacked geometry characteristic of this class of foldamer. Following heating at 80 degrees C, three of the four molecules exhibited irreversible aggregation to produce hydrogels. The hydrogels were characterized by rheology measurements, and circular dichroism spectra revealed that hydrogel formation was dependent on highly ordered intermolecular assembly, conceptually analogous to protein amyloid formation. Hydrogel formation had the effect of amplifying the subtle structural differences between molecules, as the three amphiphilic foldamer constitutional isomers that formed hydrogels upon heating displayed significant differences in hydrogel properties. Taking a global view, our results indicate that amyloid-like behavior is not unique to proteins but may be a relatively general property of amphiphilic folding molecules in aqueous solution.