DOI: 10.1002/adma.200701221 Fmoc-Diphenylalanine Self Assembles to a Hydrogel via a Novel Architecture Based on p–p Interlocked b-Sheets By Andrew M. Smith, Richard J. Williams , Claire Tang, Paolo Coppo , Richard F. Collins , Michael L. Turner, Alberto Saiani, and Rein V. Ulijn* A number of strategies exist to design molecular materials based on self-assembled peptides and their derivatives. [1] These include soft materials based on a variety of structural motifs including coiled-coils, [2,3] b-sheets, [4,5] b-hairpins, [6] and peptide amphiphiles. [7–9] In these systems, the peptide chains usually contain at least ten amino acids. It has been known for some time that using aromatic components in conjunction with peptides allows the use of much smaller peptides by tak- ing advantage of p-stacking interactions. [10–15] One system that has been illustrated is that of N-fluorenylmethoxycarbonyl di- phenylalanine (Fmoc-FF) which forms a hydrogel under phys- iological conditions. This example and other closely related aromatic short peptide derivatives are known to form fibrous hydrogels that have found applications in biological sensing [16] and cell culture. [13,17] Understanding of the supramolecular structures formed by these molecules will aid the rational design of new architectures tailored to the needs of specific biological and non-biological applications. However, to date a complete structure has not been proposed for any member of this class of self-assembly systems. Here we apply a number of spectroscopic techniques to Fmoc-FF and construct a model based on the data obtained comprising a new nanocylindrical molecular architecture based on p–p interlocked b-sheets. Transmission electron microscopy (TEM) and wide angle X-ray scattering (WAXS) was used to confirm the proposed model. Hydrogels of Fmoc-FF were prepared as described pre- viously utilizing a sequential change in pH. [13] As shown in Figure 1a self-supporting gels were formed. The viscoelastic properties of the gels were assessed using oscillatory rheology. Figure 1b shows the mechanical spectrum obtained at room temperature for a Fmoc-FF (20 mmol L –1 ) gel. The storage modulus (G’) is found to be approximately an order of magni- tude larger than the loss modulus (G’’), indicative of an elastic rather than viscous material. Both G’ and G’’ were found to be essentially independent of frequency over four decades (Fig. 1b). Such rheological behavior is characteristic of solid like gel materials. Light microscopy (Fig. 1c) revealed a net- work of fine fibers with microscopic widths. Cryo Scanning Electron Microscopy (cryoSEM) revealed a dense network of flat ribbons with dimensions in the order of tens of nanome- ters (Fig. 1d). Circular dichroism (CD) was used to investigate the back- bone orientation of the dipeptide within the hydrogel. CD analysis of peptide-based supramolecular materials is prone to artifacts. Usually only a narrow concentration range, where the hydrogel forms, can be used reliably to present a detect- able CD signal, while showing no or little light scattering ef- COMMUNICATION Adv. Mater. 2008, 20, 37–41 © 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 37 – [*] Dr. R. V. Ulijn, Dr. A. M.Smith, R. J. Williams, C. Tang, Dr. A. Saiani School of Materials, The University of Manchester Manchester, Oxford Road. M13 9PL (UK) E-mail: R.Ulijn@manchester.ac.uk Dr. P. Coppo,Dr. M. L. Turner School of Chemistry, The University of Manchester Manchester, Oxford Road. M13 9PL (UK) Dr. R. F. Collins Manchester Interdisciplinary Biocentre The University of Manchester Manchester, Oxford Road. M13 9PL (UK) [**] Supporting Information is available online from Wiley InterScience or from the authors. Figure 1. Fmoc-FF forms a self-supporting transparent hydrogel (a), rheology confirms formation of a solid like gel material (b). Its micro- scopic structure is made up of long fibrous structures as seen by the light microscopy (c). The microscopic structure as observed by cryo SEM presents flat bundles of fibers (d). Scale bars represent 10 lm and 500 nm.