Synthesis of second-generation self-assembling Gemini Amphiphilic Pseudopeptides

Abstract

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 ATR 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.

Urea-Based Low-Molecular-Weight Pseudopeptidic Organogelators for the Encapsulation and Slow Release of (R)-Limonene

“…Compounds 1b , c were prepared using a similar synthetic protocol by reaction of l -valine with either DEA or TAEA (Scheme ). The alkylurea fragments, derived from lauric acid, were introduced by the reaction of the corresponding isocyanate with the free amino groups of 1a – c , rendering the amphiphilic compounds 2a – c . , This structural design allows evaluating the effect of the geometry in optimizing the potential for intermolecular interactions via H bonds and dipolar and hydrophobic interactions, comparing bifunctional vs trifunctional systems and C 3 -symmetry tripodal systems vs those lacking such C 3 symmetry. Additionally, the selected components maximize the number of structural elements of biogenic and biocompatible nature.…”

“…Deionized water was obtained from a Milli-Q equipment. The C 2 - and C 3 - symmetrical bis- and tris­(amidoamines) were prepared as previously described. , …”

“…The C 2 -and C 3 -symmetrical bis-and tris(amidoamines) were prepared as previously described. 64,52 2.2. General Characterization Protocols.…”

“…In C 2 -symmetry pseudopeptides, the introduction of a secondary nitrogen atom in the central aliphatic spacers provides new self-assembly patterns. − This also opens the way for the preparation of new tripodal systems lacking the C 3 symmetry associated with the use of 2,2′,2″-triaminotriethylamine (TAEA) or trisubstituted aromatic derivatives as central spacers . Here, we present the development of a new family of multifunctional amphiphilic pseudopeptides derived from diethylenetriamine (DEA) or TAEA incorporating long aliphatic chains through urea linkages and displaying dipodal or tripodal character.…”

Imidazolium based gemini amphiphiles derived from L-valine. Structural elements and surfactant properties

“…In this context, previous work in our group has shown that C2-symmetric gemini amphiphilic pseudopeptides (GAPs) present a high potential for stimuli-responsive selfassembly processes. [34][35][36] In the same way, the preparation of chiral imidazolium compounds derived from amino acids, [37,38] has revealed of interest in different fields from catalysis to selective recognition, [39,40] with bis(imidazolium) derivatives of this family acting as receptors for the recognition of the chiral anions from dicarboxylic acids and as transmembrane chloride anion transporters. [41,42] In the light of the former results, here we report the synthesis of a family of gemini imidazolium surfactants derived from L-valine (2a-c, Fig.…”