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

Abstract

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.

Single Amino‐Acid Based Self‐Assembled Biomaterials with Potent Antimicrobial Activity

“…Here, hydrophobic amino acids in presence of Fmoc-group form hydrogels in the studied condition. [19] We studied the self-assembly process of amino acid derivatives into these hydrogels using different spectroscopic and microscopic techniques. Fluorescence properties of these four amino acid derivatives were examined in both solution and gel (MGC) state (Figure 2a-b).…”

Supramolecular Hydrogels: Design Strategies and Contemporary Biomedical Applications

“…The gelation process is also sensitive to processing methods, adding another layer of complexity to the problem of gelator prediction based on first principles [63] . In spite of this, the modification of LMWGs enables the precise tuning of gel properties, as minor molecular alterations or changes in conformation often translate to large physical changes at the macroscale [112] . As a result, LMWG gels have been investigated for applications such as intelligent drug release depots [113] or delivery vehicles [114,115] and molecular sensors [116] …”

“…[63] In spite of this, the modification of LMWGs enables the precise tuning of gel properties, as minor molecular alterations or changes in conformation often translate to large physical changes at the macroscale. [112] As a result, LMWG gels have been investigated for applications such as intelligent drug release depots [113] or delivery vehicles [114,115] and molecular sensors. [116] A large number of gelators exhibit at least one stereogenic centre, and chirality has been observed to play a significant role in gelation.…”

Scalable Photocatalytic Oxidation of Methionine under Continuous-Flow Conditions

“…10,23 Methionine sulfoxide 2a (Figure 1), that is, the sulfoxide of essential amino acid methionine (1a) has attracted considerable attention over the past few years. 17,24−26 It has numerous applications in studying the pathogenesis of neurodegenerative diseases, 27,28 cell aging and oxidative stress, 29 peptide sciences, 30−32 material sciences, 33,34 and in organic synthesis. 35,36 To date, only one report described the catalytic photooxidation of 1a methyl ester in D 2 O using a microfluidic setup in the presence of supported [60]fullerene PS.…”

“…Sulfoxides are found in many natural products and are important organic building blocks with tremendous applications in organic synthesis, pharmaceutical sciences, biochemistry, and material sciences. , Sulfoxides are traditionally obtained from the oxidation of sulfides with peroxides, peracids, or periodates, with optionally metal catalysts, but these methods suffer from a high risk of overoxidation to sulfones . The recent developments in catalytic photosensitized oxidations have led to robust and chemoselective oxidation procedures, either in batch , or in microfluidic devices. , Methionine sulfoxide 2a (Figure ), that is, the sulfoxide of essential amino acid methionine ( 1a ) has attracted considerable attention over the past few years. ,− It has numerous applications in studying the pathogenesis of neurodegenerative diseases, , cell aging and oxidative stress, peptide sciences, − material sciences, , and in organic synthesis. , To date, only one report described the catalytic photooxidation of 1a methyl ester in D 2 O using a microfluidic setup in the presence of supported [60]­fullerene PS . This process took advantage of 1 O 2 longer lifetime and faster oxidation kinetics in deuterated solvents, with a quantitative conversion in 33 s residence time.…”