Stereocomplexation-Promoted Alternating Supramolecular Copolymerization of Peptide-Oligo(Lactic Acid) Conjugates

Spontaneous association of multiple components into coassemblies significantly amplifies the complexity of supramolecular systems. Owing to varied noncovalent interactions, the precise regulation of the copolymerization pathway, molecular arrangement, and assembled morphology remains a huge challenge. Here, we report an intriguing system as the first example of using complementary stereocomplexation between enantiomeric oligo(lactic acid)s (oLAs) to govern the supramolecular copolymerization behavior of a series of amphiphilic peptide conjugates. Specifically, the hydrophobic chiral oLAs were conjugated to various peptides, which can self-assemble on their own in an aqueous environment into straight nanofibers with bilayer molecular packing. Upon copolymerization between two monomers with enantiomeric oLAs, helical filamentous nanostructures with an interdigitated bilayer molecular arrangement were observed. A combination of TEM imaging and spectroscopic analysis further revealed the formation of alternating microstructures in the supramolecular copolymers under thermodynamic equilibrium, promoted via stereospecific interactions between enantiomeric hydrophobic chains. In addition, the copolymerization can shift from a stereocomplexation-driven to a hydrogen-bonding-dominated process with the increase in β-sheet-forming propensity in peptides, exhibiting similar self-assembly behaviors to their homopolymer counterparts. We believe that these findings provide a new perspective on the formation of alternating supramolecular copolymers and modulation between multiple intermolecular interactions.