Internal Catalysis in Dynamic Hydrogels with Associative Thioester Cross-Links

Thioesters are an essential functional group in biosynthetic
pathways,
which has motivated their development as reactive handles in probes
and peptide assembly. Thioester exchange is typically accelerated
by catalysts or elevated pH. Here, we report the use of bifunctional
aromatic thioesters as dynamic covalent cross-links in hydrogels,
demonstrating that at physiologic pH in aqueous conditions, transthioesterification
facilitates stress relaxation on the time scale of hundreds of seconds.
We show that intramolecular hydrogen bonding is responsible for accelerated
exchange, evident in both molecular kinetics and macromolecular stress
relaxation. Drawing from concepts in the vitrimer literature, this
system exemplifies how dynamic cross-links that exchange through an
associative mechanism enable tunable stress relaxation without altering
stiffness.