Tatiana B. Kouznetsova

A backbone lever-arm effect enhances polymer mechanochemistry

Mechanical forces along a polymer backbone can be used to bring about remarkable reactivity in embedded mechanically active functional groups, but little attention has been paid to how a given polymer backbone delivers that force to the reactant. Here, single-molecule force spectroscopy was used to directly quantify and compare the forces associated with the ring opening of gem-dibromo and gem-dichlorocyclopropanes affixed along the backbone of cis-polynorbornene and cis-polybutadiene. The critical force for isomerization drops by about one-third in the polynorbornene scaffold relative to polybutadiene. The root of the effect lies in more efficient chemomechanical coupling through the polynorbornene backbone, which acts as a phenomenological lever with greater mechanical advantage than polybutadiene. The experimental results are supported computationally and provide the foundation for a new strategy by which to engineer mechanochemical reactivity.

Force-Rate Characterization of Two Spiropyran-Based Molecular Force Probes

The mechanically accelerated ring-opening reaction of spiropyran to a colored merocyanine provides a useful method by which to image the molecular scale stress/strain distribution within a polymer, but the magnitude of the forces necessary for activation has yet to be quantified. Here, we report single molecule force spectroscopy studies of two spiropyran isomers. Ring opening on the time scale of tens of milliseconds is found to require forces of ∼240 pN, well below that of previously characterized covalent mechanophores. The lower threshold force is a combination of a low force-free activation energy and the fact that the change in rate with force (activation length) of each isomer is greater than that inferred in other systems. Finally, regiochemical effects on mechanochemical coupling are characterized, and increasing force reverses the relative ring opening rates of the two isomers.

A Remote Stereochemical Lever Arm Effect in Polymer Mechanochemistry

Molecular mechanisms by which to increase the activity of a mechanophore might provide access to new chemical reactions and enhanced stress-responsive behavior in mechanochemically active polymeric materials. Here, single-molecule force spectroscopy reveals that the force-induced acceleration of the electrocyclic ring opening of gem-dichlorocyclopropanes (gDCC) is sensitive to the stereochemistry of an α-alkene substituent on the gDCC. On the ∼0.1 s time scale of the experiment, the force required to open the E-alkene-substituted gDCC was found to be 0.4 nN lower than that required in the corresponding Z-alkene isomer, despite the effectively identical force-free reactivities of the two isomers and the distance between the stereochemical permutation and the scissile bond of the mechanophore. Fitting the experimental data with a cusp model provides force-free activation lengths of 1.67 ± 0.05 and 1.20 ± 0.05 Å for the E and Z isomers, respectively, as compared to 1.65 and 1.24 Å derived from computational modeling.

Mechanical gating of a mechanochemical reaction cascade

Covalent polymer mechanochemistry offers promising opportunities for the control and engineering of reactivity. To date, covalent mechanochemistry has largely been limited to individual reactions, but it also presents potential for intricate reaction systems and feedback loops. Here we report a molecular architecture, in which a cyclobutane mechanophore functions as a gate to regulate the activation of a second mechanophore, dichlorocyclopropane, resulting in a mechanochemical cascade reaction. Single-molecule force spectroscopy, pulsed ultrasonication experiments and DFT-level calculations support gating and indicate that extra force of >0.5 nN needs to be applied to a polymer of gated gDCC than of free gDCC for the mechanochemical isomerization gDCC to proceed at equal rate. The gating concept provides a mechanism by which to regulate stress-responsive behaviours, such as load-strengthening and mechanochromism, in future materials designs.

Reactivity and Mechanism of a Mechanically Activated anti-Woodward–Hoffmann–DePuy Reaction

Mechanical forces, applied via covalent polymer mechanochemistry, have been used to bias reaction pathways and activate otherwise inaccessible reactions. Here, single-molecule polymer mechanochemistry is used to induce the disrotatory outward ring opening of a cis-dialkyl substituted syn-chloro-gem-chlorofluorocyclopropane, in violation of the Woodward-Hoffmann-DePuy (WHD) rule. The forces required to trigger the anti-WHD pathway on the ∼100 ms time scale of the experiment are about 200 pN greater than those involved in the WHD favored process (1290 vs 1500 pN). The kinetics are complemented by tension trapping experiments that suggest that the reaction proceeds along a reaction pathway that generates substantial diradicaloid character.

Single-Molecule Observation of a Mechanically Activated Cis-to-Trans Cyclopropane Isomerization

The mechanochemical activation of cis-gem-difluorocyclopropane (cis-gDFC) mechanophore in toluene was characterized with single-molecule force spectroscopy. Unlike previously reported behavior in methyl benzoate (MB), two transitions are observed in the force vs extension curves of cis-gDFC polymers in toluene. The first transition occurs at the same force of ∼1300 pN observed previously in MB, but a second transition is observed at forces of ∼1800 pN that reveal the partial formation of the trans-gDFC isomer. The behavior is attributed to competing reactions of the cis-gDFC at the 1300 pN plateau: addition of oxygen to a ring-opened diradicaloid intermediate, and isomerization of cis-gDFC to its trans isomer.

Catch and Release: Orbital Symmetry Guided Reaction Dynamics from a Freed “Tension Trapped Transition State”

The dynamics of reactions at or in the immediate vicinity of transition states are critical to reaction rates and product distributions, but direct experimental probes of those dynamics are rare. Here, s-trans, s-trans 1,3-diradicaloid transition states are trapped by tension along the backbone of purely cis-substituted gem-difluorocyclopropanated polybutadiene using the extensional forces generated by pulsed sonication of dilute polymer solutions. Once released, the branching ratio between symmetry-allowed disrotatory ring closing (of which the trapped diradicaloid structure is the transition state) and symmetry-forbidden conrotatory ring closing (whose transition state is nearby) can be inferred. Net conrotatory ring closing occurred in 5.0 ± 0.5% of the released transition states, in excellent agreement with ab initio molecular dynamics simulations.

Combined Constant-Force and Constant-Velocity Single-Molecule Force Spectroscopy of the Conrotatory Ring Opening Reaction of Benzocyclobutene

Single-molecule force spectroscopy (SMFS) of multi-mechanophore polymers has been used to provide kinetic and mechanistic insights into mechanochemical reactions. Whereas biological systems have benefitted from force clamp spectroscopy, synthetic polymers have been studied primarily with constant-velocity methods. Here, force clamp SMFS is applied to the mechanically accelerated conrotatory ring opening of benzocyclobutene, and a comparison with constant-velocity SMFS extends the range of available rate-versus-force data and corroborates the use of constant-velocity SMFS to extract force dependencies.

Substituent Effects and Mechanism in a Mechanochemical Reaction

We report the effect of substituents on the force-induced reactivity of a spiropyran mechanophore. Using single molecule force spectroscopy, force-rate behavior was determined for a series of spiropyran derivatives substituted with H, Br, or NO2 para to the breaking spirocyclic C-O bond. The force required to achieve the rate constants of ∼10 s-1 necessary to observe transitions in the force spectroscopy experiments depends on the substituent, with the more electron withdrawing substituent requiring less force. Rate constants at 375 pN were determined for all three derivatives, and the force-coupled rate dependence on substituent identity is well explained by a Hammett linear free energy relationship with a value of ρ = 2.9, consistent with a highly polar transition state with heterolytic, dissociative character. The methodology paves the way for further application of linear free energy relationships and physical organic methodologies to mechanochemical reactions, and the characterization of new force probes should enable additional, quantitative studies of force-coupled molecular behavior in polymeric materials.