Mechanochemical Approaches to Fundamental Studies in Soft-Matter Physics.

Stretching a segment of a polymer beyond its contour length makes its (primarily backbone) bonds more dissociatively labile, which enables polymer mechanochemistry. Integrating some backbone bonds into suitably designed molecular moieties yields mechanistically and kinetically diverse chemistry, which is becoming increasingly exploitable. Examples include, most prominently, attempts to improve mechanical properties of bulk polymers, as well as prospective applications in drug delivery and synthesis. This review aims to highlight an emerging effort to apply the concepts and experimental tools of mechanochemistry to fundamental physical questions in soft matter. A succinct summary of the state-of-the-knowledge of the field, with emphasis on foundational concepts and generalizable observations, is followed by analysis of 3 recent examples of mechanochemistry yielding molecular-level details of elastomer failure, macromolecular chain dynamics in elongational flows and kinetic allostery. We conclude with reasons to assume that the highlighted approaches are generalizable to a broader range of physical problems than considered to date.

Coumarin Dimer Is an Effective Photomechanochemical AND Gate for Small-Molecule Release.

Stimulus-responsive gating of chemical reactions is of considerable practical and conceptual interest. For example, photocleavable protective groups and gating mechanophores allow the kinetics of purely thermally activated reactions to be controlled optically or by mechanical load by inducing the release of small-molecule reactants. Such release only in response to a sequential application of both stimuli (photomechanochemical gating) has not been demonstrated despite its unique expected benefits. Here, we describe computational and experimental evidence that coumarin dimers are highly promising moieties for realizing photomechanochemical control of small-molecule release. Such dimers are transparent and photochemically inert at wavelengths >300 nm but can be made to dissociate rapidly under tensile force. The resulting coumarins are mechanochemically and thermally stable, but rapidly release their payload upon irradiation. Our DFT calculations reveal that both strain-free and mechanochemical kinetics of dimer dissociation are highly tunable over an unusually broad range of rates by simple substitution. In head-to-head dimers, the phenyl groups act as molecular levers to allow systematic and predictable variation in the force sensitivity of the dissociation barriers by choice of the pulling axis. As a proof-of-concept, we synthesized and characterized the reactivity of one such dimer for photomechanochemically controlled release of aniline and its application for controlling bulk gelation.

Sacrificial Mechanical Bond is as Effective as a Sacrificial Covalent Bond in Increasing Cross-Linked Polymer Toughness.

Sacrificial chemical bonds have been used effectively to increase the toughness of elastomers because such bonds dissociate at forces significantly below the fracture limit of the primary load-bearing bonds, thereby dissipating local stress. This approach owes much of its success to the ability to adjust the threshold force at which the sacrificial bonds fail at the desired rate, for example, by selecting either covalent or noncovalent sacrificial bonds. Here, we report experimental and computational evidence that a mechanical bond, responsible for the structural integrity of a rotaxane or a catenane, increases the elastomer's fracture strain, stress, and energy as much as a covalent bond of comparable mechanochemical dissociation kinetics. We synthesized and studied 6 polyacrylates cross-linked by either difluorenylsuccinonitrile (DFSN), which is an established sacrificial mechanochromic moiety; a [2]rotaxane, whose stopper allows its wheel to dethread on the same subsecond time scale as DFSN dissociates when either is under tensile force of 1.5-2 nN; a structurally homologous [2]rotaxane with a much bulkier stopper that is stable at force >5.5 nN; similarly stoppered [3]rotaxanes containing DFSN in their axles; and a control polymer with aliphatic nonsacrificial cross-links. Our data suggest that mechanochemical dethreading of a rotaxane without failure of any covalent bonds may be an important, hitherto unrecognized, contributor to the toughness of some rotaxane-cross-linked polymers and that sacrificial mechanical bonds provide a mechanism to control material fracture behavior independently of the mechanochemical response of the covalent networks, due to their distinct relationships between structure and mechanochemical reactivity.

Allosteric control of olefin isomerization kinetics via remote metal binding and its mechanochemical analysis.

Allosteric control of reaction thermodynamics is well understood, but the mechanisms by which changes in local geometries of receptor sites lower activation reaction barriers in electronically uncoupled, remote reaction moieties remain relatively unexplored. Here we report a molecular scaffold in which the rate of thermal E-to-Z isomerization of an alkene increases by a factor of as much as 104 in response to fast binding of a metal ion to a remote receptor site. A mechanochemical model of the olefin coupled to a compressive harmonic spring reproduces the observed acceleration quantitatively, adding the studied isomerization to the very few reactions demonstrated to be sensitive to extrinsic compressive force. The work validates experimentally the generalization of mechanochemical kinetics to compressive loads and demonstrates that the formalism of force-coupled reactivity offers a productive framework for the quantitative analysis of the molecular basis of allosteric control of reaction kinetics. Important differences in the effects of compressive vs. tensile force on the kinetic stabilities of molecules are discussed.

Experimental quantitation of molecular conditions responsible for flow-induced polymer mechanochemistry.

Fragmentation of macromolecular solutes in rapid flows is of considerable fundamental and practical importance. The sequence of molecular events preceding chain fracture is poorly understood, because such events cannot be visualized directly but must be inferred from changes in the bulk composition of the flowing solution. Here we describe how analysis of same-chain competition between fracture of a polystyrene chain and isomerization of a chromophore embedded in its backbone yields detailed characterization of the distribution of molecular geometries of mechanochemically reacting chains in sonicated solutions. In our experiments the overstretched (mechanically loaded) chain segment grew and drifted along the backbone on the same timescale as, and in competition with, the mechanochemical reactions. Consequently, only <30% of the backbone of a fragmenting chain is overstretched, with both the maximum force and the maximum reaction probabilities located away from the chain centre. We argue that quantifying intrachain competition is likely to be mechanistically informative for any flow fast enough to fracture polymer chains.

The molecular mechanism of constructive remodeling of a mechanically-loaded polymer.

Large or repeated mechanical loads usually degrade polymers by accelerating fragmentation of their backbones but rarely, they can cause new backbone bonds to form. When these new bonds form faster than the original bonds break, mechanical degradation may be arrested or reversed in real time. Exploiting such constructive remodeling has proven challenging because we lack an understanding of the competition between bond-forming and bond-breaking reactions in mechanically-stressed polymers. Here we report the molecular mechanism and analysis of constructive remodeling driven by the macroradical products of mechanochemical fragmentation of a hydrocarbon backbone. By studying the changing compositions of a random copolymer of styrene and butadiene sheared at 10 °C in the presence of different additives we developed an approach to characterizing this growth/fracture competition, which is generalizable to other underlying chemistries. Our results demonstrate that constructive remodeling is achievable under practically relevant conditions, requires neither complex chemistries, elaborate macromolecular architectures or free monomers, and is amenable to detailed mechanistic interrogation and simulation. These findings constitute a quantitative framework for systematic studies of polymers capable of autonomously counteracting mechanical degradation at the molecular level.

Selective ortho-C-H Activation in Arenes without Functional Groups.

Aromatic C-H activation in alkylarenes is a key step for the synthesis of functionalized organic molecules from simple hydrocarbon precursors. Known examples of such C-H activations often yield mixtures of products resulting from activation of the least hindered C-H bonds. Here we report highly selective ortho-C-H activation in alkylarenes by simple iridium complexes. We demonstrate that the capacity of the alkyl substituent to override the typical preference of metal-mediated C-H activation for the least hindered aromatic C-H bonds results from transient insertion of iridium into the benzylic C-H bond. This enables fast iridium insertion into the ortho-C-H bond, followed by regeneration of the benzylic C-H bond by reductive elimination. Bulkier alkyl substituents increase the ortho selectivity. The described chemistry represents a conceptually new alternative to existing approaches for aromatic C-H bond activation.

Force-modulated reductive elimination from platinum(ii) diaryl complexes.

Coupled mechanical forces are known to drive a range of covalent chemical reactions, but the effect of mechanical force applied to a spectator ligand on transition metal reactivity is relatively unexplored. Here we quantify the rate of C(sp2)-C(sp2) reductive elimination from platinum(ii) diaryl complexes containing macrocyclic bis(phosphine) ligands as a function of mechanical force applied to these ligands. DFT computations reveal complex dependence of mechanochemical kinetics on the structure of the force-transducing ligand. We validated experimentally the computational finding for the most sensitive of the ligand designs, based on MeOBiphep, by coupling it to a macrocyclic force probe ligand. Consistent with the computations, compressive forces decreased the rate of reductive elimination whereas extension forces increased the rate relative to the strain-free MeOBiphep complex with a 3.4-fold change in rate over a ∼290 pN range of restoring forces. The calculated natural bite angle of the free macrocyclic ligand changes with force, but 31P NMR analysis and calculations strongly suggest no significant force-induced perturbation of ground state geometry within the first coordination sphere of the (P-P)PtAr2 complexes. Rather, the force/rate behavior observed across this range of forces is attributed to the coupling of force to the elongation of the O⋯O distance in the transition state for reductive elimination. The results suggest opportunities to experimentally map geometry changes associated with reactions in transition metal complexes and potential strategies for force-modulated catalysis.

Selective, radical-free activation of benzylic C-H bonds in methylarenes.

We report rare examples of exclusive benzylic C-H oxidative addition in industrially important methylarenes using simple η4-arene iridium complexes. Mechanistic studies showed that coordinatively unsaturated η2-arene intermediates are responsible for the selective activation of benzylic, not aromatic C-H bonds and formation of stable benzyl complexes after trapping with a phosphine ligand.

Selective cleavage of unactivated arene ring C-C bonds by iridium: key roles of benzylic C-H activation and metal-metal cooperativity.

The cleavage of aromatic C-C bonds is central for conversion of fossil fuels into industrial chemicals and designing novel arene functionalisations through ring opening, expansion and contraction. However, the current progress is hampered by both the lack of experimental examples of selective oxidative addition of aromatic C-C bonds and limited understanding of the factors that favour insertion into the C-C rather than the C-H bonds. Here, we describe the comprehensive mechanism of the only reported chemo- and regioselective insertion of a transition metal into a range of substituted arene rings in simple iridium(i) complexes. The experimental and computational data reveal that this ring cleavage requires both reversible scission of a benzylic C-H bond and cooperativity of two Ir centres sandwiching the arene in the product-determining intermediate. The mechanism explains the chemoselectivity and scope of this unique C-C activation in industrially important methylarenes and provides a general insight into the role of metal-metal cooperativity in the cleavage of unsaturated C-C bonds.

The many flavours of mechanochemistry and its plausible conceptual underpinnings.

Mechanochemistry describes diverse phenomena in which mechanical load affects chemical reactivity. The fuzziness of this definition means that it includes processes as seemingly disparate as motor protein function, organic synthesis in a ball mill, reactions at a propagating crack, chemical actuation, and polymer fragmentation in fast solvent flows and in mastication. In chemistry, the rate of a reaction in a flask does not depend on how fast the flask moves in space. In mechanochemistry, the rate at which a material is deformed affects which and how many bonds break. In other words, in some manifestations of mechanochemistry, macroscopic motion powers otherwise endergonic reactions. In others, spontaneous chemical reactions drive mechanical motion. Neither requires thermal or electrostatic gradients. Distinct manifestations of mechanochemistry are conventionally treated as being conceptually independent, which slows the field in its transformation from being a collection of observations to a rigorous discipline. In this Review, we highlight observations suggesting that the unifying feature of mechanochemical phenomena may be the coupling between inertial motion at the microscale to macroscale and changes in chemical bonding enabled by transient build-up and relaxation of strains, from macroscopic to molecular. This dynamic coupling across multiple length scales and timescales also greatly complicates the conceptual understanding of mechanochemistry.

A Polymer with Mechanochemically Active Hidden Length.

Incorporating hidden length into polymer chains can improve their mechanical properties, because release of the hidden length under mechanical loads enables localized strain relief without chain fracture. To date, the design of hidden length has focused primarily on the choice of the sacrificial bonds holding the hidden length together. Here we demonstrate the advantages of adding mechanochemical reactivity to hidden length itself, using a new mechanophore that integrates (Z)-2,3-diphenylcyclobutene-1,4-dicarboxylate, with hitherto unknown mechanochemistry, into macrocyclic cinnamate dimers. Stretching a polymer of this mechanophore more than doubles the chain contour length without fracture. DFT calculations indicate that the sequential dissociation of the dimer, followed by cyclobutene isomerization at higher forces yields a chain fracture energy 11 times that of a simple polyester of the same initial contour length and preserves high energy-dissipating capacity up to ∼3 nN. In sonicated solutions cyclobutene isomerizes to two distinct products by competing reaction paths, validating the computed mechanochemical mechanism and suggesting an experimental approach to quantifying the distribution of single-chain forces under diverse loading scenarios.

Mechanochemical Regulation of Oxidative Addition to a Palladium(0) Bisphosphine Complex.

Here, we report the effect of force applied to the biaryl backbone of a bisphosphine ligand on the rate of oxidative addition of bromobenzene to a ligand-coordinated palladium center. Local compressive and tensile forces on the order of 100 pN were generated using a stiff stilbene force probe. A compressive force increases the rate of oxidative addition, whereas a tensile force decreases the rate, relative to that of the parent complex of strain-free ligand. Rates vary by a factor of ∼6 across ∼340 pN of force applied to the complexes. The crystal structures and DFT calculations support that force-induced perturbation of the geometry of the reactant is negligible. The force-rate relationship observed is mainly attributed to the coupling of force to nuclear motion comprising the reaction coordinate. These observations inform the development of catalysts whose activity can be tuned by an external force that is adjusted within a catalytic cycle.

A Mechanochemical Reaction Cascade for Controlling Load-Strengthening of a Mechanochromic Polymer.

We demonstrate an intermolecular reaction cascade to control the force which triggers crosslinking of a mechanochromic polymer of spirothiopyran (STP). Mechanochromism arises from rapid reversible force-sensitive isomerization of STP to a merocyanine, which reacts rapidly with activated C=C bonds. The concentration of such bonds, and hence the crosslinking rate, is controlled by force-dependent dissociation of a Diels-Alder adduct of anthracene and maleimide. Because the adduct requires ca. 1 nN higher force to dissociate at the same rate as that of STP isomerization, the cascade limits crosslinking to overstressed regions of the material, which are at the highest rate of material damage. Using comb polymers decreased the minimum concentration of mechanophores required to crosslinking by about 100-fold compared to previous examples of load-strengthening materials. The approach described has potential for controlling a broad range of reaction sequences triggered by mechanical load.

Mechanochromism and optical remodeling of multi-network elastomers containing anthracene dimers.

Multi-network elastomers are both stiff and tough by virtue of containing a pre-stretched stiff network that can rupture and dissipate energy under load. However, the rupture of this sacrificial network in all described covalent multi-network elastomers is irreversible. Herein, we describe the first example of multi-network elastomers with a reformable sacrificial network containing mechanochemically sensitive anthracene-dimer cross-links. These cross-links also make our elastomers mechanochromic, with coloration that is both persistent and reversible, because the fluorogenic moiety (anthracene dimer) is regenerated upon irradiation of the material. In proof-of-concept experiments we demonstrate the utility of incorporating anthracene dimers in the backbone of the sacrificial network for monitoring mechanochemical remodeling of multi-network elastomers under cycling mechanical load. Stretching or compressing these elastomers makes them fluorescent and irradiating them eliminates the fluorescence by regenerating anthracene dimers. Reformable mechanochromic cross-links, exemplified by anthracene dimers, hold potential for enabling detailed studies of the molecular origin of the unique mechanical properties of multi-network elastomers.

Ratiometric O2 sensing based on selective self-sensitized photooxidation of donor-acceptor fluorophores.

We report a series of organic fluorophores that undergo selective self-sensitized photooxidation upon light irradiation in air accompanied by a change of fluorescence from yellow to blue on the seconds timescale. The distinct emission changes allow the ratiometric quantitation of O2 concentration.

Reversible Insertion of Ir into Arene Ring C-C Bonds with Improved Regioselectivity at a Higher Reaction Temperature.

Regioselective metal insertion into aromatic C-C bonds is a long-standing problem critical for development of new arene functionalizations and cleaner conversion of fossil fuel into value-added chemicals. We report reversible insertion of iridium into the aromatic C-C bonds of η4-bound methyl arenes to give eight-membered diiridium metallacycles with yields up to 99%. While at 50-100 °C the reaction yields a mixture of isomers corresponding to iridium insertion in both unsubstituted and Me-substituted ring C-C bonds, at 150 °C a single isomer dominates. Kinetic and DFT studies suggest that at 150 °C insertion of iridium is reversible, allowing equilibration of the metallacycle products via a diiridium arene sandwich complex. The selectivity of metal insertion is determined by the relative stabilities of isomeric metallacycles governed by steric repulsion between methyl groups of the hydrocarbon chain of the cleaved arene and the Cp* ligands.

A light-driven molecular machine based on stiff stilbene.

We report a new molecular design for optically triggered nm-scale translation of a submolecular component relative to another. We used a rotaxane-like molecule terminated at one end with stiff stilbene that served both as a chromophore to trigger the translation of the pillar[5]arene "wheel" and as a stopper to prevent its dethreading.