Stimulus responsive self-assembly of Gemini Amphiphilic Pseudopeptides

Abstract

Amphiphilic amino acid derived compounds are very interesting for the design of building blocks able to self-assemble into highly ordered nanostructures, in a hierarchical and controlled fashion. With this aim, the modular synthesis and the full characterization of simple Gemini Amphiphilic Pseudopeptides (GAPs) have been carried out. These compounds were designed to establish intermolecular interactions in a hierarchical way to finally render supramolecular assemblies into well-ordered nanostructures, such as fibers, tubes, tapes or spherical vesicles. Different structural variables have been implemented, such as the amino acid side chain, the length of the central spacer and the nature of the hydrophobic tails. Besides, the effect of the environment was systematically checked, by performing the studies in solvents of different polarities (chloroform, methanol or aqueous methanol) and at different pHs (neutral, basic and acidic). The non-covalent self-assembling abilities and the structural features of the GAPs have been studied in the solid (SEM, TEM and FT-IR) and in the solution states (NMR, UV, CD, FT-IR and fluorescence spectroscopy). Moreover, the connection between the solution and the solid states has been established by monitoring the slow evaporation of the solvent by ATR FT-IR. This study has allowed the establishment of a relationship between the chemical structures of the GAPs and their abilities to form nanostructures. In some optimal cases (especially for the valine derivatives with medium-length spacers and two decyloxybenzyl hydrophobic tails), they behaved as stimulus responsive self-assembling nano-structures, which form amorphous materials from non-polar solvents, nano-fibers from polar environments at neutral or basic pH and vesicles when become protonated at acidic pH values. A reasonable structural model to explain the experimental observations can be proposed through the combination of the results from the different techniques.