Disfavoring Mechanochemical Reactions by Stress-Induced Steric Hindrance

Mechanochemical activation of covalent bonds using sonication, force spectroscopy, or molecular force probes usually lowers activation energies and thus accelerates reactions. However, applying mechanical forces to complex molecules is known to not only stretch covalent bonds but also to distort the molecular skeleton that hosts the activated bonds-leading to nonmonotonous behavior as a function of force. Here, the Bell-Taft model is introduced and validated which both rationalizes and quantifies such nonlinear effects on activation energies, including the transition from catch bonds at low forces to slip binding, in terms of steric hindrance caused by force-induced conformational distortions. The fully parametrized version of the model relies exclusively on readily accessible zero-force data and thus allows one to qualitatively explore mechanically induced reactivity changes in complex setups.