Probing assembly/disassembly of ordered molecular hydrogels

Supramolecular hydrogels have a wide range of applications in the biomedical field, acting as scaffolds for cell culture, matrices for tissue engineering and vehicles for drug delivery. L-Phenylalanine (Phe) is a natural amino acid that plays a significant role in several physiological and pathophysiological processes (phenylketonuria and assembly of fibrils linked to tissue damage). Since Myerson et al. [Chem. Eng. Commun., 2002, 189(8), 1079-1090] reported that Phe forms a fibrous network in vitro, Phe's self-assembly processes in water have been thoroughly investigated. We have reported structural control over gelation by introduction of a halogen atom in the aromatic ring of Phe, driving changes in the packing motifs, and therefore, dictating gelation functionality. The additional level of control gained over supramolecular gelation via the preparation of multi-component gel systems offers significant advantages in tuning functional properties of such materials. Gaining molecular-level information on the distribution of gelators between the inherent structural and dynamic heterogeneities of these materials remains a considerable challenge. Using multicomponent gels based on Phe and amino-L-phenylalanine (NH₂-Phe), we will explore the patterns of ordered/disordered domains in the gel fibres and will attempt to come up with general trends of interactions in the gel fibres and at the fibre/solution interfaces. Phe and NH₂-Phe were found to self-assemble in water into crystalline hydrogels. The determined faster dynamics of exchange between the gel and solution states of NH₂-Phe in comparison with Phe were correlated with weaker intermolecular interactions, highlighting the role of head groups in dictating the strength of intermolecular interactions. In the mixed Phe/NH₂-Phe systems, at a low concentration of NH₂-Phe, disruption of the network was promoted by interference of the aliphatics of NH₂-Phe with the electrostatic interactions between Phe molecules. At high concentrations of NH₂-Phe, multiple-gelator hydrogels were formed with crystal habits different from those of the pure gel fibres. NMR crystallography approaches combining the strengths of solid- and solution-state NMR proved particularly suitable to obtain structural and dynamic insights into the "ordered" fibres, solution phase and fibre/solution interfaces in these gels. These findings are supported by a plethora of experimental (diffraction, rheology, microscopy and thermal analysis) and computational methods.