Solubility-Driven Design of Multicomponent Self-Assembled Hydrogels

Abstract Nature has skillfully harnessed molecular social behavior, such as “co-assembly” and “self-sorting”, to achieve functional intricacy from simple building blocks. However, the rational control of such “social diversity” in synthetic supramolecular systems remains an unresolved problem. The entropy–enthalpy balance in hydrogelator self-assembly is a crucial thermodynamic parameter to control whether low molecular weight gelators (LMWGs) interact or act autonomously in multicomponent hydrogels. Here we propose that a simple inspection of the hydrogelator solubility vs temperature profile, as measured by 1H NMR, allows us to classify and select single-component hydrogelators in order to combine them at will. Thus, we demonstrate our hypothesis through an investigation of three individual LMWGs, with different solubility profiles, and their pairwise combinations to assess their assembly behavior over molecular, mesoscopic, and macroscopic length scales using a range of techniques. Our data show that one binary mixture exhibits co-assembly to form a unified network hydrogel material, whereas the other combinations display self-sorting, whereby each hydrogelator maintains its own structural integrity and intrinsic material properties. Crucially, temperature is used as an external stimulus to control these systems, providing direct and predictable control over material architecture. Our work highlights how simple NMR solubility measurements manifest the entropy–enthalpy balance as a rational approach to design multicomponent supramolecular materials with multifunctionality from simple and accessible molecular building blocks.