(621h) Two New Morphologies Formed By the Self-Assembly of Di-Phenylalanine in Ethanol and Acetone

Dipeptide diphenylalanine (FF) has been studied from mesoscopic to nanometric levels for its self-assembly by crystal and amorphous solid-state structures.^1,2 Diphenylalanine is the core recognition motif of Alzheimer's β-amyloid peptide, which also has the ability to self-assemble into nanotubes, nanowires, nanofibrils, and vesicles, making it suitable for a range of applications including drug delivery, 3D cell culture, and nanofabrication.³ Despite being extensively studied for constructing nanostructures, there is limited information available on the fundamental properties of diphenylalanine, such as solubility, crystallizability, and hydrate/solvate formation propensity.

In this study, the solubility of diphenylalanine dihydrate was investigated using the static method in different solvents (water, ethanol, and acetone) at 5°C and 35°C. The results showed that diphenylalanine dihydrate has an inverse solubility relationship with solvent polarity, with solubility decreasing as solvent polarity increases due to the hydrophobic side chains on the phenylalanine residues. Morphology screening experiments for diphenylalanine were also conducted in ethanol and acetone to investigate the effect of solvents on the peptide self-assembly. The PXRD patterns (as presented in Figure 1) suggest two different crystal morphologies for the diphenylalanine obtained from the cooling experiments in ethanol and acetone. Raman spectrum shows the shifting of peak at 2850-3000 cm^-1, contributed to change of the bonded C-H stretching in the new crystal structures, suggesting the different interactions between water and peptide molecules. Further, the 12% weight loss in TGA is indicative of potentially new hydrate morphology for these crystal forms. Interestingly, SEM micrographs shows the nanotubular shape for the new morphologies similar to the raw materials⁴ which has already been published as diphenylalanine dihydrate (Figure 2).

In summary, diphenylalanine exhibits new crystal from when crystallised from ethanol and acetone, which could potentially be new hydrate forms. However, further research is needed to fully understand the new crystal from and the underlying mechanisms that led to the formation.

1. Görbitz, C. H. Nanotube Formation by Hydrophobic Dipeptides. Chem. - A Eur. J. 2001, 7 (23), 5153–5159.

2. Levin, A.; Mason, T. O.; Adler-Abramovich, L.; Buell, A. K.; Meisl, G.; Galvagnion, C.; Bram, Y.; Stratford, S. A.; Dobson, C. M.; Knowles, T. P. J.; et al. Ostwalds Rule of Stages Governs Structural Transitions and Morphology of Dipeptide Supramolecular Polymers. Nat. Commun. 2014, 5 (1), 1–8.

3. Yan, X.; Zhu, P.; Li, J. Self-Assembly and Application of Diphenylalanine-Based Nanostructures. Chem. Soc. Rev. 2010, 39 (6), 1877–1890.

4. Görbitz, Carl Henrik. Nanotube Formation by Hydrophobic Dipeptides. Chem. Eur. J 2001, 7, 5153-5159.