Customizing Ionic Micelles by Dynamic Coassembly of Sequence-Defined Peptoid Block Copolymers

Monomer sequence encodes the conformation and intra- and intermolecular interactions of sequence-defined polymers. Mixing different sequences represents an attractive strategy to modulate the intra- and interchain interactions to produce mesoscale assemblies with tunable size, geometry, and internal structures, provided that mixing different sequences is thermodynamically favored over self-sorting. In this study, we investigated the aqueous assembly of binary mixtures of sequence-defined peptoid block copolymers (BCPs) with discrete chain lengths and varying charge patterns, i.e., the charge number and relative positioning along the chains. Förster Resonance Energy Transfer (FRET) experiments revealed the dynamic coassembly of peptoid chains with varying charge patterns to produce hybrid micellar aggregates. Small-angle X-ray scattering (SAXS) analysis further showed that the size and aggregation number of the hybrid micelles can be controlled by adjusting the stoichiometry of distinct sequences in the solution. Moreover, the interfacial hydrophobicity of the micellar aggregates was tailorable by the molar ratio of distinct sequences, evidenced by the binding studies with 8-anilino-1-naphthalenesulfonic acid (ANS), whose fluorescence is sensitively dependent on the polarity of its environment. This study highlights the effectiveness of producing micellar assemblies with tunable structural characteristics and interfacial hydrophobicity by mixing sequence-defined peptoid chains with varying charge patterns. This strategy expands the accessible chemical design space from a limited sequence set, paving the way for high-throughput materials discovery of micellar assemblies for different applications, such as enhanced drug encapsulation and solubilization.