Theoretical Framework for Predicting Dynamic Covalent Exchange Based on Proton Affinities and Proton-Transfer...

We provide design principles for predicting bond exchange kinetics in acylsemicarbazide (ASC)-based systems that can be applied to tuning the properties of dynamic networks. Because of their capability of dynamic and reversible bond dissociation, ASCs are promising motifs in the design of tunable dynamic covalent networks that combine mechanical robustness with reprocessability and stability. We elucidate the factors that determine the rate of bond dissociation using density functional theory in combination with detailed kinetic studies on the mechanism of the ASC dissociation. Several ASC compounds were investigated, R¹─C(═O)(H)N─N(H)─C(═O)NH─R², with R¹ methyl or phenyl, and R² methyl, phenyl, or benzoyl, that dissociate into hydrazide and isocyanate parts. The experimentally measured dissociation rate correlates with the proton affinity of the N─H bond next to R², which could also be used to predict relative dissociation rates a priori. Proton-transfer assistance is required for efficient bond exchange. A water molecule, but also neighboring ASCs (reactant) and hydrazides (product), lowers the activation barrier for bond dissociation considerably, likely facilitating autocatalysis that can occur in polymeric ASC networks. These findings can aid in the rational design of reversible polymers based on ASC motifs and can also be generalized for other dynamic covalent networks.