Bis-amide dicarboxylic acids derived from the condensation of malonic acid, 1,1-dimethylmalonic acid, 1,1-cyclopropane dicarboxylic acid, or maleic acid with L-phenylalanine, (L-Phe), are shown to supramolecularly self-assemble in aqueous solution. When basic solutions of these diacids are taken to pH 2.4, microcapsules are formed. Scanning and transmission electron micrographs confirm that microcapsules and not solid microspheres are generated. The ability of these assemblies to encapsulate other materials present during their formation in water was demonstrated with a tannic acid marker. Structure-activity studies clearly demonstrate the importance of a cis geometry between L-Phe fragments for self-assembly. Molecular modeling revealed that the cis geometry of 1a, 5a, and 14 imparts a helical structure to these systems. The subsequent self-association via hydrogen bonds of these hydrophobic helical diacids is postulated as the mechanism for their self-assembly, Nonmicrocapsule forming scaffolds (predicated on oxalic, fumaric, and succinic acid backbones) favored "cuplike" or pocket geometries which were not conducive to intermolecular aggregation.