Oxidation-Responsive Supramolecular Hydrogel Based on a Simple Fmoc-Cysteine Derivative Capable of Showing Autonomous Gel–sol–gel Transitions

Aqueous soft matter, including supramolecular hydrogels capable of exhibiting stimuli–responsive macroscopic phase transitions, has attracted increasing attention for the exploration of functional soft materials. However, the investigation of supramolecular hydrogels that undergo autonomous and multiple macroscopic phase transitions (e.g., gel–sol–gel, sol–gel–sol) in response to the surrounding environment without repeated additions of stimuli has remained largely unexplored. In this study, we present the oxidation-responsive autonomous gel–sol–gel transitions of supramolecular hydrogels fabricated via the self-assembly of a simple fluorenylmethyloxycarbonyl (Fmoc)-protected, benzylated cysteine (Fmoc-CBzl). During the evaluation of the oxidation process of Fmoc-CBzl, we found that the oxidized products, two diastereomeric sulfoxides (Fmoc-CBzl-(R)-O and Fmoc-CBzl-(S)-O), exhibit significantly different self-assembly propensities under aqueous conditions. The difference in the self-assembly propensities and kinetics of self-assembly/disassembly may contribute to oxidation-responsive autonomous gel–sol–gel transitions. Notably, the chirality of sulfoxide has been largely overlooked and not effectively used to modulate supramolecular, self-assembled nanostructures.