In Situ Heterochiral Helix Coupling Triggered Supramolecular Evolution

In situ precise matching of chiral structures (e.g., stereocomplementary pairs between secondary structures of proteins) is essential for directing the evolution of biostructures. To date, static construction of diverse stereoselective pairs (parallel homochiral or heterochiral helical array, homochiral double/triple helices, etc.) is realized by self-assembly. However, dynamically mastering helix coupling to direct structure evolution remains highly challenging due to the increased complexity of intricate chirality transfer and matching. Herein, we introduce stereochemical strategies (homochirality to racemization or mesomerization) to control heterochiral helix ( P and M ) coupling for evolving primary nanofibers into superstructures. A homochiral system is confined to initial nanofibers without evolution for over one year. In contrast, the racemization and mesomerization strategies can trigger evolution from nanofibers to superstructures after 7 h or 12 months, respectively, which are both driven by in situ generating heterochiral P – M helix coupling through the spatially matched hydrogen bonds. In a meso-system, the chiral transfer follows a strict unidirectional pathway: l -chiral terminals exclusively lead to M -helicity and D-terminals form P -helicity. However, L-fragments in a racemic system can assemble into both M and P helices through an additional conformational transformation facilitated by CH···π interactions between heterochiral fragments, revealing a rare bifurcated chirality transfer mechanism. Obviously, homochiral systems cannot achieve such helix coupling due to a lack of heterochiral interaction. This strategy thus opens a stereochemistry-controlled avenue to the in situ control of helical pairs for structural evolution.