Effect of Solvent Choice on the Self-Assembly Properties of a Diphenylalanine Amphiphile Stabilized by an Ion Pair

A diphenylalanine (FF) amphiphile blocked at the C terminus with a benzyl ester (OBzl) and stabilized at the N terminus with a trifluoroacetate (TFA) anion was synthetized and characterized. Aggregation of peptide molecules was studied by considering a peptide solution in an organic solvent and adding pure water, a KCl solution, or another organic solvent as co-solvent. The choice of the organic solvent and co-solvent and the solvent/co-solvent ratio allowed the mixture to be tuned by modulating the polarity, the ionic strength, and the peptide concentration. Differences in the properties of the media used to dissolve the peptides resulted in the formation of different self-assembled microstructures (e.g. fibers, branched-like structures, plates, and spherulites). Furthermore, crystals of TFA⋅FF-OBzl were obtained from the aqueous peptide solutions for X-ray diffraction analysis. The results revealed a hydrophilic core constituted by carboxylate (from TFA), ester, and amide groups, and the core was found to be surrounded by a hydrophobic crown with ten aromatic rings. This segregated organization explains the assemblies observed in the different solvent mixtures as a function of the environmental polarity, ionic strength, and peptide concentration.
The authors are thankful for support from MINECO and FEDER (MAT2015‐69367‐R, MAT2015‐69547‐R and CTQ2013‐40855‐R) and Gobierno de Aragón—Fondo Social Europeo (research group E40). Support for the research of C.A. was received through the prize “ICREA Academia” for excellence in research funded by the Generalitat de Catalunya.