Investigating the stability of double head to tail dimers and ribbons in multicomponent crystals of cis-4-aminocyclohexanecarboxilic acid with water and oxalic acid

The current contribution aims to investigate the stability of commonly occurring motifs present in certain amino acid structures after introducing additional molecules to form multicomponent crystals. The crystal structures of the amino acid cis-4-aminocyclohexanecarboxylic acid hemihydrate I and dehydrate II forms and that of its oxalate salt cocrystallized with oxalic acid III, were investigated employing a combination of techniques. Both single-crystal and powder X-ray diffraction were used to solve the structures, while temperature-control powder X-ray diffraction was used to follow the dehydration of I. Regardless of the added molecules that induce modifications of the intermolecular interactions within the crystals, some recurring supramolecular structures were identified: double head to tail dimers, graph symbol R ₂2(16), and ribbons, graph symbol R₂2(16)R ₃4(10). Stabilities of these supramolecular motifs were investigated using theoretical modeling with DFT/B3LYP/6-31++G (d,p) and PM6-D2H calculations. The theoretical calculations reproduced the experimental findings, confirming the extraordinary stability of these motifs. The molecular recognition of amino acid pairs to form double head to tail-dimers is undoubtedly the initial driving force for the crystal formation in all the three crystals investigated.