Ferrocenoyl Phenylalanine: A New Strategy Toward Supramolecular Hydrogels with Multistimuli Responsive Properties

In this paper we present a new paradigm for designing hydrogelators that exhibit sharp phase transitions in response to a series of disparate stimuli, including oxidation–reduction reactions (redox), guest–host interactions, and pH changes. We have serendipitously discovered that ferrocenoyl phenylalanine (Fc-F) monomers aggregate in water via a rapid self-assembly mechanism to form stable, multistimuli hydrogels. In comparison to other known mono- and multiresponsive gelators, Fc-F is unique because of its small size, economy of gel-forming components, and exceptionally simple molecular structure. Density functional theory (DFT) ab initio calculations suggest gel formation initially involves an antiparallel, noncovalent dimerization step wherein the ferrocenoyl moiety of one axe-like monomer conjoins with the phenyl group of the second monomer via a π–π stacking interaction to form brick-like dimers. This stacking creates a cavity in which the carboxylic acid groups of each monomer mutually interact via hydrogen bond formation, which affords additional stability to the dimer. On the basis of structural analysis via optical and electrical measurements and additional DFT calculations, we propose a possible stepwise hierachical assembly mechanism for fibril formation. Insights into the self-assembly pathway of Fc-F should prove useful for understanding gelation processes of more complex systems. We expect that Fc-F will serve as a helpful archetypical template for others to use when designing new, stimuli specific hydrogelation agents.