Design and self-assembly of an unconventional peptide-based dicephalic surfactant with an inverted architecture

Abstract

Surfactants with novel molecular architectures are increasingly being explored to achieve enhanced surface activity, stability, and biocompatibility. Among them, peptide-based surfactants have emerged as versatile alternatives to conventional systems due to their structural tunability and eco-friendly nature. In this study, we report the rational design and synthesis of an unconventional peptide-based dicephalic surfactant featuring a unique molecular topology, one long hydrophilic tail and two short hydrophobic heads. This configuration contrasts with traditional dicephalic surfactants, which typically possess a single hydrophobic tail and two hydrophilic heads. The hydrophilic segment comprises a collagen-derived peptide with repeating GXZ tripeptide units (G: glycine; X: proline or glutamic acid; Z: hydroxyproline or arginine), while the N-terminus is modified with di-fluorenylmethoxycarbonyl (DiFm)-functionalized L-lysine, introducing two aromatic hydrophobic heads. The resulting molecule, DiFm-GXZ, undergoes a conformational transition from a polyproline II-type single strand to a triple-helical structure. Remarkably, DiFm-GXZ exhibits excellent surface-active properties, with an exceptionally low critical aggregation concentration (CAC) of 70 µM. Self-assembly studies revealed the formation of unimicellar aggregates (∼20 nm) that further organize into higher-order multimicellar aggregates. Biophysical characterization confirmed that the self-assembly process is primarily governed by π–π stacking among aromatic groups and hydrogen bonding within the peptide backbone. The design strategy demonstrated here introduces a new class of peptide-based dicephalic surfactants with inverse architecture and tunable molecular features, offering valuable insights into the structure–property relationships governing self-assembly and interfacial behavior in peptide surfactant systems.