Hydrogelation Induced by Change in Hydrophobicity of Amino Acid Side Chain in Fmoc-Functionalised Amino Acid: Significance of Sulfur on Hydrogelation

Although a few Fmoc‐functionalised amino acids (Fmoc‐AA) are capable of forming hydrogels, the exact levels of hydrophobicity, hydrogen bonding, and ionic nature of the Fmoc‐AA gelator required for hydrogel formation remains uncertain. Here, the role of hydrophobicity of amino acid side chain, particularly in the formation of hydrogel, was studied by using Fmoc‐norleucine (Fmoc‐Nle) and its simple sulfur analogues such as Fmoc‐methionine (Fmoc‐M) in which the γCH2 of Fmoc‐Nle is replaced by sulfur. Results indicate that Fmoc‐M forms thermally reversible hydrogels in water (pH ca. 6.8), whereas Fmoc‐Nle fails to display any gelation under similar conditions. The result suggests that substitution of the sulfur atom likely reduces the hydrophobicity of the alkyl side chain in Fmoc‐Nle to the optimum level, which is sufficient to induce supramolecular hydrogelation in Fmoc‐M. The difference in the self‐association behaviour of Fmoc‐M and Fmoc‐Nle emphasise the importance of weak noncovalent interaction between side chains (in addition to the hydrogen‐bond and aromatic interactions) to stabilise supramolecular self‐assembly of Fmoc‐functionalised compounds. The current observations provide a lead to the design of new sulfur‐based low molecular weight gelators for various potential applications. Small change, big difference: A trivial change in the hydrophobicity of an amino acid side chain can convert a nongelator into a gelator in Fmoc‐functionalised amino acid by using Fmoc‐methionine and Fmoc‐norleucine.