Gelation of Fmoc-diphenylalanine is a first order phase transition

Abstract

We explore the gel transition of the aromatic dipeptide derivative molecule fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF). The addition of water to a solution of Fmoc-FF in dimethyl sulfoxide (DMSO) results in increased attractions leading to self-assembly of Fmoc-FF molecules into a space-filling fibrous network. We provide evidence that gel formation is associated with a first order phase transition resulting in nucleation and growth of strongly anisotropic crystals with high aspect ratios. The strength of attraction between Fmoc-FF molecules as a function of water concentration is estimated from long-time self-diffusion measurements using (1)H NMR diffusion-ordered spectroscopy (DOSY). The resulting phase behavior follows that observed for a wide range of other crystallizing nanoparticles and small molecules - a result consistent with the short-range nature of the intermolecular attractions. Furthermore, we use NMR to measure the rate of increase in the fraction of bound Fmoc-FF molecules after water is suddenly mixed into the system. We observe a lag time in the formation of the new phase indicative of the existence of a free energy barrier to the formation of a crystal nucleus of critical size. The application of classical nucleation theory for a cylindrical nucleus indicates that one-dimensional crystal growth is driven by an imbalance of the surface energies of the ends and sides of the fiber.

Using Rheo-Small-Angle Neutron Scattering to Understand How Functionalised Dipeptides Form Gels

“…This syneresis can be linked to the removal of charge from the self-assembled structures leading to the gel network, and hence the tendency for hydrophobic interactions to lead to the network contracting. 17 This is confirmed by again looking at tan δ; this value has stopped increasing after 250 minutes, meaning the gel network has formed, and this value remains unchanged despite the gel syneresis and the pH continuing to decrease.…”

Controlling the network type in self-assembled dipeptide hydrogels

“…The turbid to clear transition can be linked to a phase separation process. 26,30 The pH of the gels at this point is typically 3.9 AE 0.1. Gels formed by this method will be referred to as solvent-triggered gels throughout.…”

Amyloid‐Like Fibrillary Morphology Originated by Tyrosine‐Containing Aromatic Hexapeptides

“…Based on this evidence, FF became one of the prototypes of the amyloid‐based materials and many structural analogues have been synthesized and studied (e.g. : FW, FFF, PEGylated FFFF, di‐3,4‐dihydroxyphenylalanine/DOPA‐DOPA, Fmoc‐FG, and Fmoc‐FF) . In this scenario, we recently reported on the synthesis and structural characterization of a novel PEGylated Phe‐based compound, which is composed of six phenylalanine (F6) residues and eight PEG repetitive units (PEG 8 ) (PEG 8 ‐F6) …”

“…:F W, [15] FFF, [16] PEGylated FFFF, [17] di-3,4-dihydroxyphenylalanine/DOPA-DOPA, [18] Fmoc-FG, [19] and Fmoc-FF). [20] In this scenario, we recently reported on the synthesis and structural characterization of an ovel PEGylatedP he-based compound,w hich is composed of six phenylalanine (F6) residues and eight PEGrepetitive units (PEG 8 )( PEG 8 -F6). [21] This peptide-polymer conjugate is ablet os elf-assemble in stable and well-organized nanostructures endowed with a cross-b structure.…”