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 ≈2-decade range of Keq’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.

下一代柔性可回收材料的开发，其核心特征在于主客体（host-guest）、超分子（supramolecular）以及动态共价（dynamic covalent）等动态（可逆）化学体系。动态体系可赋予材料可注射性、可再加工性以及随时间演化的力学性能。这类性能源于分子连接点（交联点，cross-links）的速率与平衡常数（RECs）之间的内在关联，以及由此产生的动态网络宏观行为。然而，在探索分子性能与材料性能之间的关联时，鲜有研究会对RECs进行明确测量，针对聚合物水凝胶（polymeric hydrogel）体系的此类研究尤为稀缺。本研究借助动态共价亚胺（imine）形成反应，探究氨基端亲核试剂（NH2-terminated nucleophiles）的单点组成变化对结合常数（binding constants）以及所得水凝胶力学性能的影响。我们同时开展了小分子模型体系与聚合物大分子单体（macromers）模型研究，发现RECs存在超过3个数量级的变化。借助文献中已确立的相关关联，我们随后构建了一个简单模型，用于描述交联平衡过程并预测水凝胶力学性能的变化。值得注意的是，我们观察到一个狭窄的≈2个数量级的平衡常数（Keq）范围即可决定亚胺的结合分数。借助该模型，我们揭示了一种特殊机制：在交联达到饱和前添加交联剂，反而会降低水凝胶的交联密度（cross-link density）。随后我们通过实验验证了这一预测行为的正确性。值得一提的是，这类新出现的行为并未被现有共价水凝胶理论所涵盖。本研究拓展了亚胺形成反应的结构-反应性（structure-reactivity）关联关系，凸显了定量测定RECs对宏观行为预测的助力作用。此外，尽管本研究聚焦于动态共价亚胺形成反应，其核心原理可推广至柔性可回收动态材料的通用自下而上（bottom-up）设计。