Tailoring Dynamic Hydrogels by Controlling Associative Exchange Rates

Dithioalkylidenes are a recently-developed class of conjugate acceptors that undergo thiol exchange via an associative mechanism and have been used for reprocessable vitrimers, amine sensors, and degradable networks. Here, we show that the exchange rate of the reaction in aqueous environments is highly sensitive to the structure of the acceptor and may be varied over four orders of magnitude. Cyclic acceptors exchange rapidly, from 0.95 to 15.6 M-1s-1, while acyclic acceptors exchange between 3.77x10-3 and 2.17x10-2 M-1s-1. Computational, spectroscopic, and structural data suggest that the cyclic acceptors are more reactive than their linear counterparts because of resonance stabilization of the tetrahedral intermediate. We leverage this insight to design a compound with reactivity intermediate to that of the cyclic and linear analogs. Lastly, we incorporate this dynamic bond into hydrogels and demonstrate that molecular kex correlates with the hydrogels characteristic stress relaxation time; furthermore, these values may be parametrized with respect to computed descriptors of the electrophilic site. This work opens new avenues to design and control hydrogel viscoelasticity with an associative exchange mechanism.