Hydrogels can be formed by the self-assembly of certain small molecules in water. Self-assembly occurs via non-covalent interactions. The self-assembly leads to the formation of fibrous structures which form the matrix of the gel. The mechanical properties of the gels arise from the properties of the fibres themselves (thickness, persistence length etc.), the number and type of cross-links and also how the fibres are distributed in space (the microstructure). We discuss here the effect of assembling the molecules under different conditions, i.e. the self-assembly process. There is sufficient literature showing that how the molecules are assembled can have a significant effect on the properties of the resulting gels.

Controlling the order and spatial distribution of self-assembly in multicomponent supramolecular systems could underpin exciting new functional materials, but it is extremely challenging. When a solution of different components self-assembles, the molecules can either coassemble, or self-sort, where a preference for like-like intermolecular interactions results in coexisting, homomolecular assemblies. A challenge is to produce generic and controlled 'one-pot' fabrication methods to form separate ordered assemblies from 'cocktails' of two or more self-assembling species, which might have relatively similar molecular structures and chemistry. Self-sorting in supramolecular gel phases is hence rare. Here we report the first example of the pH-controlled self-sorting of gelators to form self-assembled networks in water. Uniquely, the order of assembly can be predefined. The assembly of each component is preprogrammed by the pK a of the gelator. This pH-programming method will enable higher level, complex structures to be formed that cannot be accessed by simple thermal gelation.

Fmoc-diphenylalanine (FmocFF or FmocPhePhe) is an important low molecular weight hydrogelator. Gelation can be induced by either lowering the pH of an aqueous solution of FmocFF or by the addition of water to a solution of FmocFF in a solvent such as DMSO. Despite the volume of literature on FmocFF, the mechanical properties reported for the gels vary significantly over four orders of magnitude and the origins of this variability is unclear. Here, we study systematically the mechanical properties of FmocFF gels prepared with different protocols. We demonstrate that the final pH of the gels is the principal determinant of the mechanical properties independently of the method of gel formation. We also show that additional variability arises from experimental factors such as the fraction of DMSO or the nature of the buffers used in selected systems.Scheme 1 Structure of FmocFF.Scheme 2 Hydrolysis of GdL to gluconic acid.

Low molecular weight gelators (LMWG) self-assemble in solution into one-dimensional objects such as fibres or tapes. The entanglement of these fibres or tapes results in the formation of a network and a gel. In general, LMWG are investigated as single component systems. However, there are significant potential opportunities from mixed LMWG systems, which are rarely investigated. Here, we discuss the potential of multicomponent systems, and critically discuss the challenges.

Gels can be formed by dissolving Fmoc-diphenylalanine (Fmoc-PhePhe or FmocFF) in an organic solvent and adding water. We show here that the choice and amount of organic solvent allows the rheological properties of the gel to be tuned. The differences in properties arise from the microstructure of the fibre network formed. The organic solvent can then be removed post-gelation, without significant changes in the rheological properties. Gels formed using acetone are meta-stable and crystals of FmocFF suitable for X-ray diffraction can be collected from this gel.

The mechanical properties of gels are critical to the final targeted applications. Depending on the application, different properties may be required. Here, we show that the mechanical strength and ability to recover of gels formed using a low molecular weight gelator can be controlled by two independent factors (i) the volume fraction of co-solvent (in this case DMSO) in the system and (ii) the temperature cycle used. These differences correlate with the large scale structure of the network that is formed from the self-assembled fibres. This opens up the potential to prepare gels with very different properties at the same final conditions, allowing the effect of microstructure to be probed.Scheme 1 Structure of FmocLG.

A number of Fmoc amino acids can be effective low molecular weight hydrogelators. The type of gel formed depends on the amino acid used and, in the case of FmocF, the final pH of the system. The single crystal structure of two of the gelators (FmocF and FmocY) have been determined and the data compared to the fibre X-ray diffraction data. FmocF, which forms metastable gels, crystallises easily and the data for the fibre phase and crystal phase are relatively similar. For FmocF, the fibre axis in b is consistent with the hydrogen bonding repeat distances and the diffraction pattern calculated from the single crystal structure is a good match with the experimental fibre X-ray diffraction data. On the other hand, there are significant differences between the crystalline phase determined and the fibre phase for FmocY. The packing of FmocY within the crystal structure is created by interactions between the planar Fmoc groups, whilst it is clear that hydrogen bonding drives the self-assembly into fibrillar structures within the gels. This shows that understanding the packing in gel phase by analogy to isolated crystal structures has the potential to lead to erroneous conclusions. CrystEngCommThis journal is

Novel block copolymers comprising poly(ethylene glycol) (PEG) and an oligo(tyrosine) block were synthesized in different compositions by N-carboxyanhydride (NCA) polymerization. It was shown that PEG2000-Tyr(6) undergoes thermoresponsive hydrogelation at a low concentration range of 0.25-3.0 wt % within a temperature range of 25-50 °C. Cryogenic transmission electron microscopy (Cryo-TEM) revealed a continuous network of fibers throughout the hydrogel sample, even at concentrations as low as 0.25 wt %. Circular dichroism (CD) results suggest that better packing of the β-sheet tyrosine block at increasing temperature induces the reverse thermogelation. A preliminary assessment of the potential of the hydrogel for in vitro application confirmed the hydrogel is not cytotoxic, is biodegradable, and produced a sustained release of a small-molecule drug.