Steering chemical reactions with force

Abstract

Chemical reactivity underlies our fundamental understanding of many physical and biological phenomena. Chemical reactions are typically initiated by heat, electric current or light. Albeit far less studied, mechanical force is yet another way to orthogonally catalyse chemical reactions. An applied force can substantially reduce the reaction energy barrier, thus enabling reaction pathways that are too slow (or even forbidden) according to the laws of thermodynamics. Single-molecule nanomechanical techniques, including optical and magnetic tweezers and atomic force microscopy, offer the possibility to apply a directional force on an individual chemical bond. In non-covalent (or soft) mechanochemistry, low, sub-nN forces trigger bond rotation or hydrogen-bond rupture. By contrast, in covalent mechanochemistry, higher forces typically result in the breaking and re-forming of individual bonds. This Review focuses on the advances in our mechanistic understanding of single-bond mechanochemistry resulting from single-molecule measurements, as well as on the exciting new perspectives that we envision for this burgeoning field in the near future.

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Figure 1: The magnitude of the externally applied force determines the degree of mechanical disruption of the bond under force.
Figure 2: Non-covalent mechanochemistry on biopolymers.
Figure 3: Covalent mechanochemistry on synthetic polymers.
Figure 4: Covalent mechanochemistry: the homolytic rupture of covalent bonds.
Figure 5: Covalent mechanochemistry: the heterolytic rupture of covalent disulfide bonds.
Figure 6: The force dependency of disulfide bond rupture.
Figure 7: The (reversible) reformation of individual disulfide bonds within the context of oxidative folding determines protein nanomechanics.

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Acknowledgements

The authors apologize to the many colleagues whose work could not be cited owing to space constraints. A.E.M.B. thanks the Engineering and Physical Sciences Research Council (EPSRC) for funding through an EPSRC DTP fellowship. This work was supported by a Marie Curie Career Integration Grant (No. 293462), a Biotechnology and Biological Sciences Research Council grant (No. J00992X/1), a Royal Society Research grant (No. RG120038), a British Heart Foundation grant (No. PG/13/50/30426), an EPSRC Fellowship (No. K00641X/1) and a Leverhulme Trust Research Leadership Award, all to S.G.-M.

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Both authors researched data for the article and contributed to discussion of content. A.E.M.B. wrote part of the covalent mechanochemistry section, and S.G.-M. wrote the rest of the article. Both authors reviewed and edited the manuscript.

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Correspondence to Sergi Garcia-Manyes.

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Glossary

Amylose

A homopolymer of α-D-glucopyranose rings in which C1 is bonded to C4 on the consecutive ring through a glycosidic bond.

Dextran

A homopolymer formed by glycosidic bonds linking C1 and C6 of consecutive α-D-glucopyranose rings.

Freely jointed chain (FJC) model

A model that describes the behaviour of a semi-flexible polymer composed of rigid and inextensible segments, which are free to rotate at any angle with no correlation between the directions of the neighbouring segments. Under purely thermal control, the polymer will reside in a maximum entropy random configuration. As mechanical force is applied, the polymer stretches against an entropic force resulting from the reduced number of available conformations under force.

Worm-like chain (WLC) model

An extension of the freely jointed chain model that takes into account the energetic costs for bending the polymer chain. Single-molecule nanomechanical techniques are best suited for characterizing the force-dependent stretching behaviour of various polymers.

Woodward–Hoffmann–DePuy (WHD) rule

A rule describing the conservation of orbital symmetry for reactions that have a transition state with cyclic geometry.

Ligand K-edge X-ray absorption spectroscopy

An experimental technique that can be used to investigate the degree of covalency of a metal–ligand bond. The K-edge of the absorption spectra is generated by the excitation of the ligand 1s electron to an empty p orbital, providing information on the atomic arrangement at the active site of a metalloprotein.

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Garcia-Manyes, S., Beedle, A. Steering chemical reactions with force. Nat Rev Chem 1, 0083 (2017). https://doi.org/10.1038/s41570-017-0083

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