Stimuli-responsive microgels cross-linked through supramolecular interactions of peptides

Stimuli-responsive microgels are colloidal polymer networks and the nature of the cross-links governs their ability to undergo reversible structural and topological changes in response to environmental stimuli such as temperature, pH, light, ionic strength, and mechanical force. Herein, we exploit the supramolecular interactions of the aromatic L-phenylalanyl-L-phenylalanine (Phe-Phe) dipeptide motif as a supramolecular cross-linker to fabricate poly-N-vinylcaprolactam (PVCL)-based thermoresponsive microgels. In the present work, we synthesize a series of microgels with variable content of Phe-Phe cross-links and quantify their amount (0.3-37 mol%) by nuclear magnetic resonance (¹H NMR) spectroscopy. We demonstrate that Phe-Phe cross-links retain the integrity and colloidal stability of microgels in aqueous solutions. Circular dichroism (CD) spectroscopy is employed to investigate aromatic π-π stacking of Phe moieties, confirming the formation of supramolecular cross-links. An increase in the Phe-Phe content or a decrease in microgel size induces temperature-dependent aggregation, which can be leveraged for the preparation of condition-guided microgel assemblies. Furthermore, we investigate solvent-induced degradation of physical cross-linking and dipeptide concentration-controlled morphological changes in the obtained microgels.