Forcing the reversibility of a mechanochemical reaction

Abstract

Mechanical force modifies the free-energy surface of chemical reactions, often enabling thermodynamically unfavoured reaction pathways. Most of our molecular understanding of force-induced reactivity is restricted to the irreversible homolytic scission of covalent bonds and ring-opening in polymer mechanophores. Whether mechanical force can by-pass thermodynamically locked reactivity in heterolytic bimolecular reactions and how this impacts the reaction reversibility remains poorly understood. Using single-molecule force-clamp spectroscopy, here we show that mechanical force promotes the thermodynamically disfavored SN2 cleavage of an individual protein disulfide bond by poor nucleophilic organic thiols. Upon force removal, the transition from the resulting high-energy unstable mixed disulfide product back to the initial, low-energy disulfide bond reactant becomes suddenly spontaneous, rendering the reaction fully reversible. By rationally varying the nucleophilicity of a series of small thiols, we demonstrate how force-regulated chemical kinetics can be finely coupled with thermodynamics to predict and modulate the reversibility of bimolecular mechanochemical reactions.

The nanomechanics of individual proteins

“…45 Notably, an important finding in these mechanochemistry experiments is that mechanical force can by-pass thermodynamical restrictions, implying that it can catalyse chemical reactions that would be otherwise unfavored from the classical thermodynamic perspective. 46 Applying the force-quench protocol to the resulting mechanical unfolded and chemically reduced proteins allows monitoring oxidative folding-the mechanism by which mechanical folding encompasses the reformation of the original, natively-formed disulfide bonds (Fig. 12).…”

Diffusion of lithium ions in Lithium-argyrodite solid-state electrolytes

“…The field adds a force to the particles in the direction of the field, and has a similar effect to reducing the activation energy barrier for diffusion 52 . If the diffusion process can be modelled as a jump process, the expected time for a single jump will increase exponentially with the size of the activation barrier, and therefore application of the field will allow systems with much lower diffusion coefficients to be considered for a given simulation time.…”

High force catch bond mechanism of bacterial adhesion in the human gut

“…pathways [28][29][30] and receptor-ligand interactions [31][32][33][34] . Singlemolecule FRET (smFRET) is capable of measuring distances at the molecular scale 35 , and has been used to study protein dynamics 36,37 and to characterize structures of receptor-ligand complexes 38,39 .…”