Tailoring dynamic hydrogels by controlling associative exchange rates

Dithioalkylidenes are a newly developed class of conjugate acceptors that undergo thiol exchange via an associative mechanism, enabling decoupling of key material properties for sustainability, biomedical, and sensing applications. Here, we show that the exchange rate is highly sensitive to the structure of the acceptor and tunable over four orders of magnitude in aqueous environments. Cyclic acceptors exchange rapidly, from 0.95 to 15.6 M−1s−1, whereas acyclic acceptors exchange between 3.77 × 10−3 and 2.17 × 10−2 M−1s−1. Computational, spectroscopic, and structural data suggest that cyclic acceptors are more reactive than their acyclic counterparts because of resonance stabilization of the tetrahedral exchange intermediate. We parametrize molecular reactivity with respect to computed descriptors of the electrophilic site and leverage this insight to design a compound with intermediate characteristics. Lastly, we incorporate this dynamic bond into hydrogels and demonstrate that the characteristic stress relaxation time (τ) is directly proportional to molecular kex. [Display omitted] •Dynamic conjugate addition-elimination of thiols to dithioalkylidenes in water•Fabrication of viscoelastic hydrogels with associatively exchanging cross-links•Correlation of macromolecular trends with molecular rate constants•Prediction of macromolecular trends based on computed molecular descriptors Dynamic covalent bonds have enabled key advances in sustainable materials, biomedicine, and 3D printing. Materials containing dynamic bonds exhibit unique properties compared with their static counterparts, such as self-healing, reprocessability, and stimuli responsiveness. In hydrogels, dynamic bonds provide a mechanism to dissipate applied stress, which can be exploited to develop synthetic materials that recapitulate the mechanical features of native tissue. We develop a suite of hydrogel cross-links that employs an associative exchange mechanism, allowing stress relaxation to be tuned independently from stiffness. We present a structure-reactivity-property relationship that enables reactivity and stress relaxation timescales to be estimated in silico for new structures. This work, therefore, opens new avenues to design and control associative dynamic hydrogels with targeted properties, overcoming the limitations of previous systems that have largely relied on dissociative exchange mechanisms. Dithioalkylidene conjugate acceptors undergo dynamic exchange with thiols, endowing