Improved methodologies are provided to synthesize (1R,2S)-2-aminocyclobutane-1-carboxylic acid derivatives and their incorporation into β-peptides of 2–8 residues bearing different N-protecting groups. The conformational analysis of these oligomers has been carried out by using experimental techniques along with theoretical calculations. This study shows that these oligomers adopt preferentially a strand-type conformation in solution induced by the formation of intra-residue six-membered hydrogen-bonded rings, affording cis-fused [4.2.0]octane structural units that confer high rigidity on these β-peptides. Moreover, all of them are prone to self-assemble producing nano-sized fibres, as evidenced by TEM, AFM and SPFM, and, in some instances, they also form gels. These techniques and molecular modelling allowed us to suggest an aggregation model for the assembly structures in which a parallel molecular-arrangement is preferred and the conformation is similar to that observed in solution. According to this model, both hydrogen-bonding and hydrophobic interactions would account for formation of the assemblies.

Some hybrid tetrapeptides consisting of (1R,2S)-2-aminocyclobutane-1-carboxylic acid and glycine, β-alanine, or γ-aminobutyric acid (GABA) joined in alternation, compounds 1–3, respectively, have been investigated to gain information on the non-covalent interactions responsible for their self-assembly to form ordered aggregates, as well as on parameters such as their morphology and size. All three peptides formed nice gels in many organic solvents and significant difference in their behaviour was not observed. Scanning electron microscopy (SEM) and circular dichroism (CD) pointed out that peptide 1, which contains the shortest C₂ linear residue, presented the most defined fibril network and afforded nanoscale helical aggregates. Tetrapeptide 3, with C₄ linear residues in its structure, also showed bundles of fibres whereas a homogeneous spherulitic network was observed for tetrapeptide 2, with a C₃ spacer between cyclobutane residues. Computational calculations for 1 allowed us to model the self-assembly of the molecules and suggested a head-to-head arrangement to give helical structures corresponding to hydrogen-bonded single chains. These features were corroborated by a high-resolution NMR spectroscopy study of the dynamics of the gelation process in toluene-d₈ which evidenced that molecules self-assemble to afford ordered aggregates with a supramolecular chirality.

A homochiral synthetic dipeptide incorporating two cyclobutyl rings has been used as an assembling unit for the π-electron-rich tetrathiafulvalene (TTF) moiety. The molecule was prepared and characterised to show all the features of the two components, whereby chirality and π-function are incorporated in the same species. Supramolecular fibres are formed by the compound, as proven by atomic force microscopy (AFM) and transmission electron microscopy. The dimensions of the nanostructures suggest that the molecules pack into dimeric tapes with the peptide head groups at the centre. Current-sensing AFM shows that once doped, films of the material are capable of conducting electricity.