Self‐Assembly of a β‐Peptide Foldamer: The Role of the Surfactant in Three‐Dimensional Shape Selection

Abstract

The effect of a small ionic surfactant, cetyltrimethylammonium bromide (CTAB), on the self‐assembly of a β‐peptide has been systematically studied by using scanning electron microscopy, X‐ray diffraction, selected area electron diffraction, and molecular dynamics (MD) simulations. The latter study suggested that the formation of asymmetric microcrystals may be due to the preferential adsorption of CTAB on {011} and (001) crystal faces. This work provides a plausible rationale for the characteristic 3D morphogenesis of foldectures and elucidates the interaction between the surfactant and organic building block molecules.

The Diverse World of Foldamers: Endless Possibilities of Self-Assembly

“…The greatest efforts in the field of β-peptide with well-defined and amazing solid tridimensional (3D) structures, different from the simpler morphologies described in the previous subsection, have been due to Lee’s group, who coined the term “foldecture” (from foldamer and architecture) [ 131 , 132 , 133 , 134 , 135 , 136 , 137 ]. Foldectures are actually self-assembled crystalline solids formed in nonequilibrium conditions, and the molecular packing can be either quite similar or very different from that obtained in single crystals grown in equilibrium conditions.…”

“…However, in the presence of P123, its micelles differentially solvated the windmill at an early stage, thus greatly decreasing the growth in two directions (x and y) in favor of the longitudinal growth, as depicted by z in Figure 8 c. In a further study, the addition of an oligomer shortened by one unit, the hexamer Boc-ACPC 6 -OBn, as shown in Figure 8 a (n = 6), to a 8 g L −1 aqueous solution of P123 led to the very peculiar molar tooth-shaped (M P ) morphology, as shown in Figure 8 d [ 132 ]. The resulting self-assembled structure was again the result of a differential solvation by means of P123 micelles, as ascertained by changing the experimental temperatures above or below the critical micellar temperature, as shown in Figure 8 e. The preferential adsorption of a different (cationic) surfactant, namely cetyltrimethylammonium bromide (CTAB), onto the different facets of the growing self-assembled structure of the same β-hexapeptide, Boc-ACPC 6 -OBn, was further studied [ 137 ]. Powder X-ray diffraction (PXRD) data of the different morphologies obtained, as shown in Figure 9 a, highlighted that all these Boc-ACPC 6 -OBn-based foldectures, as well as those obtained using P123 as surfactant, basically had the same molecular packing, characterized by extremely similar intra and intermolecular hydrogen bonds and hydrophobic interactions among the foldameric units.…”

“… ( a ) General structure of trans -ACPC oligomers investigated (both S , S and R , R absolute stereochemistries were employed) (Refs. [ 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 ]); ( b ) SEM images of structures self-assembled from Boc-ACPC 7 -OBn in distilled water (W W ) and in a 0.03 g L −1 aqueous solution of P123 (R P ) (scale bars: 1 µm, adapted with permission from Ref. [ 131 ]); ( c ) Rationale for the surfactant-based changes in the self-assembled structures of Boc-ACPC 7 -OBn in distilled water and in an aqueous solution of surfactant P123: after the initial fast nucleation, the growth in pure water is faster along the x and y axes, due to the presence of the most hydrophobic foldamer moieties, thus favoring tip elongation and creating the windmill-shaped (W W ) morphologies.…”

“… ( a ) SEM images of morphologies obtained from Boc-ACPC 6 -OBn in (from left to right) 0.05, 0.2, 0.3, 2, 5, and 10 g L −1 aqueous CTAB solutions (scale bars: 1 µm, adapted with permission from Ref. [ 137 ]); ( b ) Relationship between 3D shape of a foldecture and increasing concentration of CTAB (reprinted with permission from Ref. [ 137 ]); ( c ) SEM images of the self-assembled structures of Boc-ACPC 6 -OH from distilled water (F 1 , upper) and aqueous P123 solution 8 g L −1 (F 2 , lower) (adapted with permission from Ref.…”

Formation and Modulation of Nanotubular Assemblies of Oligourea Foldamers in Aqueous Conditions using Alcohol Additives

“…In this respect, the use of additives provides an appealing approach to study and modulate the aqueous self‐assembly process of foldamers. Indeed, the control of self‐assembling properties of natural biopolymers using small molecule additives has been studied in detail, while few examples have been reported for foldamer building blocks …”