Biomimetic Design of a Robustly Stabilized Folded State Enabling Seed-Initiated Supramolecular Polymerization under Microfluidic Mixing.

We have investigated the folding and assembly behavior of a cystine-based dimeric diamide bearing pyrene units and solubilizing alkyl chains. In low-polarity solvents, it forms a 14-membered ring through double intramolecular hydrogen bonds between two diamide units. The spectroscopic studies revealed that the folded state is thermodynamically unstable and eventually transforms into more energetically stable helical supramolecular polymers that show an enhanced chiral excitonic coupling between the transition dipoles of the pyrene units. Importantly, compared to an alanine-based monomeric diamide, the dimeric diamide exhibits a superior kinetic stability in the metastable folded state, as well as an increased thermodynamic stability in the aggregated state. Accordingly, the initiation of supramolecular polymerization can be regulated using a seeding method even under microfluidic mixing conditions. Furthermore, taking advantage of a self-sorting behavior observed in a mixture of l-cysteine- and d-cysteine-based dimeric diamides, a two-step supramolecular polymerization was achieved by stepwise addition of the corresponding seeds.

Hydrophobicity-driven folding and seeded polymerization of cystine-based dimeric diamides in aqueous media.

Seeded supramolecular polymerization of cystine-based dimeric diamides with aromatic substituents at the C- and N-termini was achieved in aqueous media. Theoretical and spectroscopic studies reveal that the terminal groups play crucial roles in slowing spontaneous assembly through formation of a folded conformation and guiding molecular alignment in the aggregated state.

Seeded Polymerization through the Interplay of Folding and Aggregation of an Amino-Acid-based Diamide.

Amino acid based diamides are widely used as a substructure in supramolecular polymers and are also key components of polypeptides that help to understand protein folding. The interplay of folding and aggregation of a diamide was used to achieve seed-initiated supramolecular polymerization. For that purpose, a pyrene-substituted diamide was synthesized in which pyrene is used as a tracer to monitor the supramolecular polymerization. Thermodynamics and time-dependent studies revealed that the folding of the diamide moiety, via the formation of intramolecular hydrogen bonds, effectively prevents a spontaneous nucleation that leads to supramolecular polymerization. Under such out-of-equilibrium conditions, the addition of seeds successfully initiates the supramolecular polymerization. These results demonstrate the utility of such amino acid based diamides in programmable supramolecular polymerizations.