Mediating Oxidation of Thioethers with Iodine - A Mild and Versatile Pathway to Trigger the Formation of Peptide Hydrogels

Nowak BP, Schlichter L, Ravoo BJ

Abstract

The development of redox-triggerable peptide hydrogels poses fundamental challenges, since the highly specific peptide architectures required inevitably limit the versatility of such materials. A powerful, yet rarely applied approach to bypass those barriers is the application of a mediating redox reaction to gradually decrease the pH during hydrogel formation. We report a versatile strategy to trigger the formation of peptide hydrogels from readily accessible acid-triggerable gelators by generating protons by oxidation of thioethers with triiodide. Adding thiodiglycol as a readily available thioether auxiliary to the basic precursor solution of a peptide gelator efficiently yielded hydrogels after mixing with triiodide, as studied in detail for Nap-FF and demonstrated for other peptides. Furthermore, incorporation of the thioether moiety in the gelator backbone via the amino acid methionine as shown for the tailormade Nap-FMDM peptide provides a useful modulation option reducing the number of additives.