Synthesis of second-generation self-assembling Gemini Amphiphilic Pseudopeptides

Hypothesis: The structural modularity of Gemini Amphiphilic Pseudopeptides (GAPS) allows the tuning of the self-assembling properties by slight modifications in the chemical structures. We hypothesized that the introduction of a flexible linker containing a central nitrogen atom in bipodal and tripodal GAPs would improve their self-assembly properties in aqueous media. Experiments: After preparation of the corresponding GAPs, a combination of SEM, TEM and AFM techniques were used to study the morphology of the self-assembled structures in different media. The solution structures in non-aggregated states were also analyzed by combining NMR, UV and CD studies. The transition from the non-aggregated species to the hierarchical self-assembly was monitored by AIR FT-IR spectroscopy, while the critical aggregation concentration in water was determined by fluorescence spectroscopy. Findings: The formation of different morphologies (vesicles or fibers) highly depends on the polarity and the pH of the medium. A reasonable mechanism for the self-assembly has been established in agreement with the experimental techniques used, where the protonation of the nitrogen in the linker must play a key role. In general, the obtained GAPs showed an improved formation of vesicles in aqueous media (different pH or ionic strength) with potential applications in biomedicine and drug delivery. (C) 2019 Elsevier Inc. All rights reserved.