Self-Assembly Mechanism for a Naphthalene−Dipeptide Leading to Hydrogelation

Abstract

Suitably functionalized dipeptides have been shown to be effective hydrogelators. The design of the hydrogelators and the mechanism by which hydrogelation occurs are both currently not well understood. Here, we have utilized the hydrolysis of glucono-delta-lactone to gluconic acid as a means of adjusting the pH in a naphthalene-alanylvaline solution allowing the specific targeting of the final pH. In addition, this method allows the assembly process to be characterized. We show that assembly begins as charge is removed from the C-terminus of the dipeptide. The removal of charge allows lateral assembly of the molecules leading to pi-pi stacking (shown by CD) and beta-sheet formation (as shown by IR and X-ray fiber diffraction). This leads to the formation of fibrous structures. Electron microscopy reveals that thin fibers form initially, with low persistence length. Lateral association then occurs to give bundles of fibers with higher persistence length. This results in the initially weak hydrogel becoming stronger with time. The final mechanical properties of the hydrogels are very similar irrespective of the amount of GdL added; rather, the time taken to achieving the final gel is determined by the GdL concentration. However, differences are observed between the networks under strain, implying that the kinetics of assembly do impart different final materials' properties. Overall, this study provides detailed understanding of the assembly process that leads to hydrogelation.

Structural determinants in a library of low molecular weight gelators

“…Attempts to identify molecular structure-property relationships have so far characterised aspects of the molecular architectures of dipeptide self-assembled fibrils using methods such as computational structure prediction, powder diffraction (pXRD), X-ray crystallography, wide angle X-ray scattering (WAXS) and X-ray fibre diffraction (fXRD). 3,20,22 Each of these techniques has revealed a great deal of structural information on the systems studied. 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.…”

“…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.…”

“…19 In addition to the plethora of molecular hydrogels with varying material properties available, the morphology of the constituent fibrils making these gels is reported to vary extensively: fibrils, laterally associated fibrils, helical-ribbons, ribbons and tapes, and nanotubes have all been reported to result from the assembly of peptidic LMWG. [20][21][22][23] It is known that the self-assembled structures for these classes of molecule are often stabilised by extended hydrogen bonded networks of ß-strands and π-π aromatic interactions. 3,20,22,24 Despite the limited range of noncovalent stabilising interactions, these molecules have access to a large and elaborate range of supramolecular structures which give rise to variable morphologies, presumably due to the large degrees of freedom available in three-dimensional packing motifs and subtle difference in the energies of intermolecular interactions.…”

“…[20][21][22][23] It is known that the self-assembled structures for these classes of molecule are often stabilised by extended hydrogen bonded networks of ß-strands and π-π aromatic interactions. 3,20,22,24 Despite the limited range of noncovalent stabilising interactions, these molecules have access to a large and elaborate range of supramolecular structures which give rise to variable morphologies, presumably due to the large degrees of freedom available in three-dimensional packing motifs and subtle difference in the energies of intermolecular interactions. It has been suggested that particular molecular structures may give rise to a pre- determined morphology which would, in turn, have a predictable impact on the properties of subsequent rheological properties of the hydrogel formed.…”

“…In the other five dipeptides where exciton couplets associated with the naphthalene groups are observed, this indicates that the naphthalene chromophores are subject to highly organised chiral stacking, as previously observed. 20 The sign of the Cotton effect associated with each naphthalene exciton couplet indicates the handedness of the chiral arrangement is related to the dipeptide sequence. The peptide sequence determined the handedness: dipeptides with the sequence AlaVal have a left-handed helical naphthalene arrangement and those with the sequence Ala-Ala have the converse righthanded arrangement (Table 1 In addition to successfully assigning each couplet to its naphthalene chromophore, the hypochromic decrease of the naphthalene groups is revealed by deriving the absorbance changes over the course of self-assembly (Supplementary Figure 5).…”