On Crystal versus Fiber Formation in Dipeptide Hydrogelator Systems

Abstract

Naphthalene dipeptides have been shown to be useful low-molecular-weight gelators. Here we have used a library to explore the relationship between the dipeptide sequence and the hydrogelation efficiency. A number of the naphthalene dipeptides are crystallizable from water, enabling us to investigate the comparison between the gel/fiber phase and the crystal phase. We succeeded in crystallizing one example directly from the gel phase. Using X-ray crystallography, molecular modeling, and X-ray fiber diffraction, we show that the molecular packing of this crystal structure differs from the structure of the gel/fiber phase. Although the crystal structures may provide important insights into stabilizing interactions, our analysis indicates a rearrangement of structural packing within the fibers. These observations are consistent with the fibrillar interactions and interatomic separations promoting 1D assembly whereas in the crystals the peptides are aligned along multiple axes, allowing 3D growth. This observation has an impact on the use of crystal structures to determine supramolecular synthons for gelators.

Low-Molecular-Weight Gels: The State of the Art

“…Indeed, although it has been widely assumed that there is a link, there are a number of examples that now specifically show that packing is different in the gel phase and crystals grown even from the same solvent. [24][25][26] As a specific example, we showed that fiber X-ray diffraction data from the gel phase did not match the crystal structure of a crystal grown directly from the gel phase. 24 In many cases, the crystals formed in one solvent are compared with a gel formed in another.…”

Structural determinants in a library of low molecular weight gelators

“…Hydrated fibre X-ray diffraction 10 µL of gelating solution (5 mgmL-1) was suspended between two wax capillaries immediately after GdL dissolution in a dehydration cell similar to devices reported elsewhere 48 and as previously reported 25 . Diffraction data were collected at the point of fibril alignment whilst still in the hydrated state.…”

“…However, as shown by Adams et al, whilst the crystalline phase of LMWG assemblies is related to computational structure predictions, the structure of final fibre phase for these systems remains elusive. 18,25 It is apparent that crystals and fibres have structural features in common, but also show fundamental differences. 25 For investigations relevant to the gel phase, it is essential to interrogate the structure of selfassembled LMWG in the fibre phase.…”

“…18,25 It is apparent that crystals and fibres have structural features in common, but also show fundamental differences. 25 For investigations relevant to the gel phase, it is essential to interrogate the structure of selfassembled LMWG in the fibre phase. We have previously reported on the detailed structural characterisation of two LMWG systems in the assembled fibrillar phase 20,25 benefitting from the additional directional information granted by fXRD and revealing a highly organised repetitive arrangement of the molecules along the fibre axis.…”

“…25 For investigations relevant to the gel phase, it is essential to interrogate the structure of selfassembled LMWG in the fibre phase. We have previously reported on the detailed structural characterisation of two LMWG systems in the assembled fibrillar phase 20,25 benefitting from the additional directional information granted by fXRD and revealing a highly organised repetitive arrangement of the molecules along the fibre axis. Here, we have investigated a set of dipeptide sequences containing alanine (A) and valine (V) conjugated to naphthalene (Nap) groups containing Br, CN or H to probe the contribution of different parts of the molecule to the structural architectures.…”