Molecular Catch Bonds and the Anti-Hammond Effect in Polymer Mechanochemistry

Abstract

While the field of polymer mechanochemistry has traditionally focused on the use of mechanical forces to accelerate chemical processes, theoretical considerations predict an underexplored alternative: the suppression of reactivity through mechanical perturbation. Here, we use electronic structure calculations to analyze the mechanical reactivity of six mechanophores, or chemical functionalities that respond to mechanical stress in a controlled manner. Our computational results indicate that appropriately directed tensile forces could attenuate (as opposed to facilitate) mechanochemical phenomena. Accompanying experimental studies supported the theoretical predictions and demonstrated that relatively simple computational models may be used to design new classes of mechanically responsive materials. In addition, our computational studies and theoretical considerations revealed the prevalence of the anti-Hammond (as opposed to Hammond) effect (i.e., the increased structural dissimilarity between the reactant and transition state upon lowering of the reaction barrier) in the mechanical activation of polyatomic molecules.

Resolving the molecular mechanism of cadherin catch bond formation

“…These include energy landscapes with one bound state and two unbinding pathways 43 ; an energy landscape with two bound states, one of which is preferentially stabilized by force 44,45 ; bond dissociation along a multidimensional landscape where the direction of the tensile force and the reaction coordinate are misaligned [46][47][48] ; a freeenergy landscape with dynamic disorder that thermally fluctuates with time 49,50 ; and allosteric deformation models where external force changes the structure of the receptor either directly at the ligand-binding site 51 or at a distal location that ultimately propagates the deformation to the binding pocket [52][53][54][55] . Our simulations suggest that X-dimers form catch bonds via a slidingrebinding mechanism where a pulling force flexes the ectodomain and slides opposing EC1 domains resulting in the formation of de novo, force-induced H-bonds.…”

Perspective: Mechanochemistry of biological and synthetic molecules

“…Indeed, an analysis of all possible pulling scenarios involving pairs of pulling points and applied to 6 known mechanophores showed that the compliance χ TS is positive for all of them. 4 We note, however, that, for highly symmetric molecules, the alignment between the pulling direction and the steepest descent coordinate may result from symmetry.…”

“…Contrary to the theoretical arguments presented above and despite computational evidence of multidimensional effects, 4,[73][74][75][76] one-dimensional models are widely used to (successfully) fit single-molecule force spectroscopy data, with experimental evidence of multidimensional behavior limited to only a handful of reports.…”

“…What distinguishes the mechanochemical approach to manipulating chemical reactivity is that force, unlike temperature, pressure, or solvent composition, is a vector, and merely altering its direction via a change in the attachment points can drastically alter the observed kinetics. [2][3][4] While industrial applications of mechanochemistry are yet few, numerous processes in the living cell rely on the coupling between mechanical and chemical phenomena. Molecular motors, for example, convert chemical energy into mechanical work, which is used to contract muscles, transport cargo across cells, or package DNA within virus shells.…”

“…The probability of a fortuitous alignment between the pulling direction and the steepest descent direction thus becomes negligible as the dimensionality D increases. 4 Of course, it is the experimental design and the molecular structure, rather than random chance, that determine the directions of the pulling force and of the steepest descent path. Still, the above probabilistic argument suggests that the alignment of the two directions is likely to occur only if deliberately designed by the experimenter; and even then such an experiment may be impossible because the required pulling direction in the D-dimensional space will require forces to be applied to all the atoms of the molecule, not just two of them.…”