Complementary π-π Interactions Induce Multicomponent Coassembly into Functional Fibrils

Noncovalent self-assembled materials inspired by amyloid architectures are useful for biomedical applications ranging from regenerative medicine to drug delivery. The selective coassembly of complementary monomeric units to provide ordered multicomponent fibrils is a possible strategy for enhancing the sophistication of these noncovalent materials. Herein we report that complementary pi-pi interactions can be exploited to promote the coassembly of phenylalanine (Phe) derivatives that possess complementary aromatic side chain functionality. Specifically, equimolar mixtures of Fmoc-Phe and Fmoc-F-5-Phe, which possess side-chain groups complementary quadrupole electronics, readily coassemble to form two-component fibrils and hydrogels under conditions where Fmoc-Phe alone fails to self-assemble. In addition, it was-found that equimolar mixtures of Fmoc-Phe with monohalogenated (F, Cl and Br) Fmoc-Phe derivatives also coassembled into two-component fibrils. These results collectively indicate that face-to-face quadrupole stacking between benzyl side-chain groups does not account for the molecular recognition between Phe and halogenated Phe derivatives that promote cofibrillization but that coassembly is mediated by more subtle pi-pi effects arising from the halogenation of the benzyl side chain. The use of complementary pi-pi interactions to promote the coassembly of two distinct monomeric units into ordered two-component fibrils dramatically expands the repertoire of noncovalent that can be used in the development of sophisticated noncovalent materials.