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

Abstract

AbstractWe 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.