Protection of Oxygen-Sensitive Enzymes by Peptide Hydrogel

Molecular oxygen (O 2 ) is a highly reactive oxidizing agent and is harmful to many biological and industrial systems. Although O 2 often interacts via metals or reducing agents, a binding mechanism involving an organic supramolecular structure has not been described to date. In this work, the prominent dipeptide hydrogelator fluorenylmethyloxycarbonyl-diphenylalanine is shown to encage O 2 and significantly limit its diffusion and penetration through the hydrogel. Molecular dynamics simulations suggested that the O 2 binding mechanism is governed by pockets formed between the aromatic rings in the supramolecular structure of the gel, which bind O 2 through hydrophobic interactions. This phenomenon is harnessed to maintain the activity of the O 2 -hypersensitive enzyme [FeFe]-hydrogenase, which holds promising potential for utilizing hydrogen gas for sustainable energy applications. Hydrogenase encapsulation within the gel allows hydrogen production following exposure to ambient O 2 . This phenomenon may lead to utilization of this low molecular weight gelator in a wide range of O 2 -sensitive applications.