Modification of a Single Atom Affects the Physical Properties of Double Fluorinated Fmoc-Phe Derivatives

• Published in: International journal of molecular sciences Vol. 22; no. 17; p. 9634
• Main Authors: Aviv, Moran, Cohen-Gerassi, Dana, Orr, Asuka A., Misra, Rajkumar, Arnon, Zohar A., Shimon, Linda J. W., Shacham-Diamand, Yosi, Tamamis, Phanourios, Adler-Abramovich, Lihi
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.09.2021; MDPI
• Subjects: Computer applications; Crystal structure; Fluorination; Fluorine; Hydrogels; Kinetics; low-molecular-weight hydrogelator; Mechanical properties; Molecular dynamics; Molecular structure; Morphology; Phase transitions; phase-transition; Physical properties; Physicochemical properties; Rheology; Self-assembly; Solvents; Tissue engineering; Viscoelasticity; X-ray diffraction
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22179634

Supramolecular hydrogels formed by the self-assembly of amino-acid based gelators are receiving increasing attention from the fields of biomedicine and material science. Self-assembled systems exhibit well-ordered functional architectures and unique physicochemical properties. However, the control over the kinetics and mechanical properties of the end-products remains puzzling. A minimal alteration of the chemical environment could cause a significant impact. In this context, we report the effects of modifying the position of a single atom on the properties and kinetics of the self-assembly process. A combination of experimental and computational methods, used to investigate double-fluorinated Fmoc-Phe derivatives, Fmoc-3,4F-Phe and Fmoc-3,5F-Phe, reveals the unique effects of modifying the position of a single fluorine on the self-assembly process, and the physical properties of the product. The presence of significant physical and morphological differences between the two derivatives was verified by molecular-dynamics simulations. Analysis of the spontaneous phase-transition of both building blocks, as well as crystal X-ray diffraction to determine the molecular structure of Fmoc-3,4F-Phe, are in good agreement with known changes in the Phe fluorination pattern and highlight the effect of a single atom position on the self-assembly process. These findings prove that fluorination is an effective strategy to influence supramolecular organization on the nanoscale. Moreover, we believe that a deep understanding of the self-assembly process may provide fundamental insights that will facilitate the development of optimal amino-acid-based low-molecular-weight hydrogelators for a wide range of applications.