Monomer exchange dynamics in ureido-pyrimidinone supramolecular polymers via molecular simulations

The use of synthetic supramolecular polymers, built with monomers that self-assemble via non-covalent, reversible interactions, is rapidly growing in many fields, including energy, environmental, and bioengineering applications. Very recently, ureido-pyrimidinone (UPy)-based supramolecular polymers have been used to synthesize biocompatible hydrogels aiming to mimic the dynamic environment of extracellular matrices. Tuning the dynamics, stiffness, and bioactivity of UPy hydrogels effectively influences cellular behaviour and tissue development. However, a complete understanding of UPy-network dynamics over different length and time scales is still lacking, and even the most advanced experimental approaches are unable to capture the dynamics of monomer exchange with atomistic resolution. Here we present a computational study on UPy supramolecular assemblies in water that uncovers the mechanism of monomer exchange between the UPy supramolecular polymers and their surroundings. Our results, based on atomistic molecular dynamics (MD) simulations combined with enhanced sampling and machine-learning (ML) techniques, show that the fine interplay of solute-solvent interactions is the main engine of monomer motion, which makes UPy supramolecular polymer ends more dynamic as compared to the static backbone. This computational work complements the qualitative experimental evidence on supramolecular dynamics with the mechanism of monomer exchange, revealing the most favorable environment for supramolecular polymer damage as well as the underlying principle of self-healing.