Multicomponent low molecular weight gelators

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

Understanding the self-assembly process and tunability of the final properties of dipeptide-based low molecular weight hydrogels

Reported in this thesis is the ability to prepare a number of dipeptide-conjugate hydrogels with tunable final properties, through judicious choice of the assembly conditions and gelator structure. Gelation of these materials can be triggered by solvent-mediated, pH-triggered, UV-triggered and electrochemically-induced means to give different mechanical properties. Subtle changes in the assembly conditions can evoke changes in the final properties - something that was evident across a range of gelator systems and methods of triggering gelation. UV and electrochemical methods demonstrated the ability to spatially and temporally control gelation, which could be of potential use to biosensor and cell culturing applications. Molecular rotors could be employed to monitor the kinetics of the gelation process, indicating an evolution in self-assembled structure around the pKa of a gelator. This thesis highlights the importance of the self-assembly process on the final properties of dipeptide-conjugate gels. A better understanding of this process will be beneficial for gelator design. Where specific hydrogel properties are needed, the gelator will be tunable for a desired application by manipulating the assembly conditions

Morpholino Oligonucleotide Cross-Linked Hydrogels as Portable Optical Oligonucleotide Biosensors

© 2018 American Chemical Society. Morpholino Oligonucleotides (MOs), an uncharged DNA analogue, are functionalized with an acrylamide moiety and incorporated into polymer hydrogels as responsive cross-links for microRNA sequence detection. The MO cross-links can be selectively cleaved by a short target analyte single-stranded DNA (ssDNA) sequence based on microRNA, inducing a distinct swelling response measured optically. The MO cross-links offer significant improvement over DNA based systems through improved thermal stability, no salt requirement and 1000-fold improved sensitivity over a comparative biosensor, facilitating a wider range of sensing conditions. Analysis was also achieved using a mobile phone camera, demonstrating portability

Using molecular rotors to probe gelation

A series of fluorescent probes, including a number of molecular rotors, have been used to follow the self-assembly of dipeptide-based low molecular weight gelators. We show that these probes can be used to gain an insight into the assembly process. Thioflavin T, a commonly used stain for β-sheets, appears to act as a molecular rotor in these gelling systems, with the fluorescence data closely matching that of other rotors. The molecular rotor was incorporated into an assay system with glucose oxidase to enable glucose-concentration specific gelation and hence generating a fluorescent output. Applying this system to urine from patients with various levels of glycosuria (a symptom of diabetes), it was found to provide excellent correlation with different clinical assessments of diabetes. This demonstrates a new concept in gelation-linked biosensing for a real clinical problem

The effect of solvent choice on the gelation and final hydrogel properties of Fmoc–diphenylalanine

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

Dipeptide hydrogelation triggered via ultraviolet light

UV irradiation of a dipeptide gelator in solution with a photoacid generator (PAG) results in the formation of a hydrogel. We demonstrate that photopatterning of these gels using a UV mask is possible

The importance of the self-assembly process to control mechanical properties of low molecular weight hydrogels

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

Fmoc-diphenylalanine hydrogels: understanding the variability in reported mechanical properties

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

Supramolecular Hydrogels with Reverse Thermal Gelation Properties from (Oligo)tyrosine Containing Block Copolymers

Novel block copolymers comprising poly­(ethylene glycol) (PEG) and an oligo­(tyrosine) block were synthesized in different compositions by <i>N</i>-carboxyanhydride (NCA) polymerization. It was shown that PEG2000-Tyr₆ 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

Chemically programmed self-sorting of gelator networks

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 pKa of the gelator. This pH-programming method will enable higher level, complex structures to be formed that cannot be accessed by simple thermal gelatio