Structure-Reactivity Relationships in a Small Library of Imine-Type Dynamic Covalent Materials: Determination of Rate and Equilibrium Constants Enables Model Prediction and Validation of a Unique Mechanical Softening in Dynamic Hydrogels

The development of next generation soft and recyclable materials prominently features dynamic (reversible) chemistries such as host-guest, supramolecular, and dynamic covalent. Dynamic systems enable injectability, reprocessability, and time-dependent mechanical properties. These properties arise from the inherent relationship between the rate and equilibrium constants (RECs) of molecular junctions (cross-links) and the resulting macroscopic behavior of dynamic networks. However, few examples explicitly measure RECs while exploring this connection between molecular and material properties, particularly for polymeric hydrogel systems. Here we use dynamic covalent imine formation to study how single-point compositional changes in NH2-terminated nucleophiles affect binding constants and resulting hydrogel mechanical properties. We explored both model small molecule studies and model polymeric macromers, and found >3-decade change in RECs. Leveraging established relationships in the literature, we then developed a simple model to describe the cross-linking equilibrium and predict changes in hydrogel mechanical properties. Interestingly, we observed that a narrow approximate to 2-decade range of K-eq's determine the bound fraction of imines. Our model allowed us to uncover a regime where adding cross-linker before saturation can decrease the cross-link density of a hydrogel. We then demonstrated the veracity of this predicted behavior experimentally. Notably this emergent behavior is not accounted for in covalent hydrogel theory. This study expands upon structure-reactivity relationships for imine formation, highlighting how quantitative determination of RECs facilitates predicting macroscopic behavior. Furthermore, while the present study focuses on dynamic covalent imine formation, the underlying principles of this work are applicable to the general bottom-up design of soft and recyclable dynamic materials.