The delicate balance between gelation and crystallisation: structural and computational investigations

Predicting the ability of low molecular weight molecules to form hydrogels is difficult. Here, we have examined the self-assembly behavior of two chemically and structurally similar functionalized dipeptides, one of which is found to form a meta-stable hydrogel (1) and the other forming a crystalline solid (2). To investigate the reasons for these differences, we have employed computational methods to explore the crystal energy landscapes of the two molecules and examined differences in their preferred packing arrangements. We show that this method accurately predicts the packing for the crystalline solid, 2. Furthermore, the predictions for the gel-former 1 suggest that one-dimensional hydrogen-bonding arranged into tightly coiled molecular columns is a preferred mode of packing for this system, but is unfavorable for 2. The different tendencies of forming these columns could provide an explanation for the different behavior of the two molecules and demonstrate that this approach could be useful for the future predictable design of low molecular weight gelators.