Chemomechanics with molecular force probes

Chemomechanics is an emerging area at the interface of chemistry, materials science, physics, and biology that aims at quantitative understanding of reaction dynamics in multiscale phenomena. These are characterized by correlated directional motion at multiple length scales-from molecular to macroscopic. Examples include reactions in stressed materials, in shear flows, and at propagating interfaces, the operation of motor proteins, ion pumps, and actuating polymers, and mechanosensing. To explain the up to 10(15)-fold variations in reaction rates in multiscale phenomena-which are incompatible within the standard models of chemical kinetics-chemomechanics relies on the concept of molecular restoring force. Molecular force probes are inert molecules that allow incremental variations in restoring forces of diverse reactive moieties over hundreds of piconewtons (pN). Extending beyond the classical studies of reactions of strained molecules, molecular force probes enable experimental explorations of how reaction rates and restoring forces are related. In this review, we will describe the utility of one such probe-stiff stilbene. Various reactive moieties were incorporated in inert linkers that constrained stiff stilbene to highly strained macrocycles. Such series provided the first direct experimental validation of the most popular chemomechanical model, demonstrated its predictive capabilities, and illustrated the diversity of relationships between reaction rates and forces.