Machine-readable line notations such as SMILES are rapidly gaining popularity as a means of storing, searching, and analyzing chemical information. Within the SMILES framework, BigSMILES was developed to represent the stochastic connectivity characteristics of polymers. More recently, noncovalent BigSMILES extended the notation to encode noncovalent interactions, recognizing the stochastic nature of these bonds. Inspired by this framework, Topological BigSMILES is introduced to provide a further extension to represent topological interactions in macromolecules. This notation appends optional topological bond descriptors and associated indices, enabling the annotation of complex molecular architectures. In particular, the notation presented herein can encode the topological interactions found in knotted macrocycles and polymers, polycatenanes, and polyrotaxanes. The progression from BigSMILES to Topological BigSMILES highlights the potential for this framework to be used in representing broader classes of soft materials systems.

The tearing of a polymer network arises from mechanochemically coupled bond-breaking events in the backbone of a polymer chain. An emerging research area is the identification of molecular strategies for network toughening, such as the strategic placement of mechanochemically reactive groups (e.g., scissile mechanophores) in the crosslinks of a network instead of in the load-bearing primary strands. These mechanically labile crosslinkers have typically relied on release of ring strain or weak covalent bonds for selective covalent bond scission. Here, we report a novel chemical design for accelerated mechanochemical bond scission based on replacing a single carbon atom in a crosslinker with a silicon atom. This single-atom replacement affords up to a two-fold increase in the tearing energy. We suggest a mechanism, validated by computational modeling, for accelerated mechanochemical Si-C bond scission based on minimizing the energy required to distort the starting material toward the transition-state geometry. We demonstrated the seamless incorporation of these scissile carbosilanes to toughen 3D-printed networks, which demonstrates their suitability for additive manufacturing processes.

Oxy-substituted gem-dihalocyclopropanes (gDHCs) have recently found utility as mechanoacids for the generation of HCl or HF following force-assisted ring opening along polymer backbones. Here, we employ single-molecule force spectroscopy (SMFS) to quantify how oxy substituents influence the force-coupled kinetics of activation in gem-dichlorocyclopropane (gDCC) and gem-difluorocyclopropane (gDFC) mechanophores. Multimechanophore polymers bearing the desired mechanophores are pulled to high forces of extension until their reaction is observed as a plateau in the force-extension curves. At tip retraction velocities of 300 nm s-1, we find that oxy substituents reduce the plateau force associated with the reaction by more than 400 pN relative to unsubstituted analogs. The force reduction is greater for gDFC than gDCC, and main-chain oxy substituents reduce the requisite force by approximately 100 pN relative to pendant oxy substituents. The reactivity patterns are rationalized in terms of the accepted mechanisms of the reactions. The results help guide the design of polymer backbones for efficient mechanoacid activation.

The stretchability (ability to be elongated) and toughness (capacity to absorb energy before breaking) of polymer network materials, such as elastomers and hydrogels, often determine their utility and lifetime. Direct correlations between the molecular behavior of polymer network components and the physical properties of the network inform the design of materials with enhanced performance, extended lifetime, and minimized waste stream. Here, we report the impact of the fused ring size in bicyclic cyclobutane mechanophores within the strands of polymer network gels. The mechanophores and their polymer strands share the same initial covalent contour length, whereas the capacity for reactive strand extension (RSE) is varied by changing the size of the ring fused to the cyclobutane from 5 to 12 carbon atoms. We observe the first evidence of covalent RSE effects in a single-network gel, and strands with greater RSE lead to gels with greater stretchability and toughness. The same qualitative correlation between molecular and macroscopic extension is also observed in DN hydrogels with mechanophores in the prestretched first network.

Understanding structure-mechanical activity relationships (SMARs) in polymer mechanochemistry is essential for the rational design of mechanophores with desired properties, yet SMARs in noncovalent mechanical transformations remain relatively underexplored. In this study, we designed a subset of diarylethene mechanophores based on a lever-arm hypothesis and systematically investigated their mechanical activity toward a noncovalent-yet-chemical conversion of atro-pisomer stereochemistry. Results from DFT calculations, single-molecule force spectroscopy (SMFS) measurements, and ultrasonication experiments collectively support the lever-arm hypothesis and confirm the exceptional sensitivity of chemo-mechanical coupling in these atropisomers. Notably, the transition force for the diarylethene M3 featuring extended 5-phenylbenzo[b]thiophene aryl groups is determined to be 131 pN ± 4 pN by SMFS. This value is lower than typically recorded for other mechanically induced chemical processes, highlighting its exceptional sensitivity to low-magnitude forces. This work contributes a fundamental understanding of chemo-mechanical coupling in atropisomeric configurational mechanophores and paves the way for designing highly sensitive mechanochemical processes that could facilitate the study of nanoscale mechanical behaviors across scientific disciplines.

Natural rubber has many uses in a variety of industries, enabled by ‘crosslinking’ between its tangled polymers, which creates elasticity. But rubber can crack and suffer fatigue. It is now shown that reducing the crosslink density in highly entangled natural rubber increases its crack resistance and prolongs its useful life.

Symmetry forbidden reactions are notoriously difficult to study experimentally, for the simple reason that their competing symmetry allowed pathways typically dominate. Covalent polymer mechanochemistry offers an opportunity to broaden access to symmetry forbidden reactions, through the judicious placement of polymer handles on mechanophore reactants. Here, single molecule force spectroscopy and computation are used to evaluate substituent effects on the disrotatory ring opening reaction of cyclobutene to butadiene. Theory and experiment reveal that the formally forbidden reaction is more sensitive to substituents on the scissile carbon-carbon bond than on the alkene, with each of two Me substituents providing approximately 1.5-2 kcal mol-1 of stabilization and a trimethylsilyl alkyne substituent approximately 4.5-6.5 kcal mol-1.

The specific three-dimensional structure, e.g. the chirality, of the product of many important reactions is determined in large part by the structure of a catalyst, for example the ligand around a metal center, that makes the reaction tractable. Here, we demonstrate that the chiral selectivity of the hydrogenation of a methyl 2-amidoacrylate via a fixed bisphosphine Rh catalyst can be improved by embedding that catalyst into an appropriate heterogenous elastomeric support and transducing the mechanical deformation of the elastomer to the catalyst. The ratio of R and S product isomers is strain-dependent and reversible upon relaxing the support. Stretching the support by 50% in a single dimension increases the R:S ratio of the product by up to 32%.

Thermoset toughness and deconstructability are often opposing features; simultaneously improving both without sacrificing other mechanical properties (e.g., stiffness and tensile strength) is difficult, but, if achieved, could enhance the usage lifetime and end-of-life options for these materials. Here, a strategy that addresses this challenge in the context of photopolymer resins commonly used for 3D printing of glassy, acrylic thermosets is introduced. It is shown that incorporating bis-acrylate "transferinkers," which are cross-linkers capable of undergoing degenerative chain transfer and new strand growth, as additives (5-25 mol%) into homemade or commercially available photopolymer resins leads to photopolymer thermosets with substantially improved tensile toughness and triggered chemical deconstructability with minimal impacts on Young's moduli, tensile strengths, and glass transition temperatures. These properties result from a transferinker-driven topological transition in network structure from the densely cross-linked long, heterogeneous primary strands of traditional photopolymer networks to more uniform, star-like networks with few dangling ends; the latter structure more effectively bear stress yet is also more easily depercolated via solvolysis. Thus, transferinkers represent a simple and effective strategy for improving the mechanical properties of photopolymer thermosets and providing a mechanism for their triggered deconstructability.

Mechanophores are molecules that undergo chemical changes in response to mechanical force, offering unique opportunities in chemistry, materials science, and drug delivery. However, many potential mechanophores remain unexplored. For example, ferrocenes are attractive targets as mechanophores due to their combination of high thermal stability and mechanochemical lability. However, the mechanochemical potential of ferrocene derivatives remains dramatically underexplored despite the synthesis of thousands of structurally diverse complexes. Herein, we report the computational, machine learning guided discovery of synthesizable ferrocene mechanophores. We identify over one hundred potential target ferrocene mechanophores with wide-ranging mechanochemical activity and use data-driven computational screening to identify a select number of promising complexes. We highlight design principles to alter their mechanochemical activation, including regio-controlled transition state stabilization through bulky groups and a change in mechanism through noncovalent ligand-ligand interactions. The computational screening is validated experimentally both at the polymer strand level through sonication experiments and at the network level, where a computationally discovered ferrocene mechanophore cross-linker leads to greater than 4-fold enhancement in material tearing energy. This work establishes a generalizable framework for the high-throughput discovery and rational design of mechanophores and offers insights into structure-activity relationships in mechanically responsive materials.

Herein, we report that molecular tension generated by the swelling of a polyacrylate network containing a chiral [Biphep]Rh(I) catalyst as a tension-bearing, bis-tethered cross-linker enhances the enantioselectivity of hydrogenation of methyl 2-acetamidoacrylate. Differential swelling of the network is achieved by changing the relative concentrations of toluene (low swelling) and dichloromethane (high swelling) cosolvents. Swelling is characterized by the ratio of final to initial length in a single dimension of the network (λ = lf/li), noting that changes are the same in all dimensions; λx = λy = λz. The enantiomeric excess (ee) of the hydrogenation reaction increases monotonically with λ, from 22% ee at λ = 1.53 to 39% ee at λ = 1.77. Control networks in which the catalyst is appended as a tension-free pendant side chain functionality display a minor change in ee as a function of swelling (ee = -0.7 ± 3.1%) with no obvious correlation between the two. The change in enantioselectivity due to swelling of the mechanically coupled network for a given λ is greater than when the same λx and λy are generated from the uniaxial compression along the normal z-axis, a result that is attributed to the isotropic strain associated with swelling in three dimensions rather than stretching in two dimensions. The results suggest that solvent swelling may provide a previously untapped modality for exploiting force-coupled catalysis in practical and scalable platforms, including those adapted from current polymer-supported catalysts.

The reactivity and selectivity of a transition metal catalyst is intimately related to its ligand-sphere geometry, and, in many cases, the ideal ligand geometry for one step of a catalytic cycle is poorly matched to the ideal ligand geometry for another. For this reason, methods for reversibly modulating ligand geometry on the time scale of catalytic turnover or monomer enchainment are highly desirable. Mechanical force represents a heretofore untapped approach to modulate catalyst geometry and/or reactivity, with the potential to do so on the timescale of catalytic turnover or monomer enchainment. Macroscopic mechanical forces are large, directional and localized to an extent that differentiates them from other forms of energy input such as heat or light. In this Concept, we describe our efforts to address the fundamental challenges associated with force-modulated transition metal catalysis by employing molecular force probe ligands comprising a stiff stilbene photoswitch tethered to rotationally flexible biaryl bisphosphine ligand. Our efforts to date include the modulation of catalytic activity through force-mediated ligand perturbations, quantification of the force-coupled ligand effects on the energetics of elementary organometallic transformations, and evaluation of the mechanisms of force transduction in these systems. Molecular force probe ligands apply a controlled force of extension or compression to the ligand scaffold of an intact transition metal bisphosphine complex. Using these ligands, we have quantified the effect of force on the rates of elementary reactions, namely oxidative addition and reductive elimination, and on the selectivities of catalytic transformations including the palladium-catalyzed Heck coupling and rhodium-catalyzed hydroformylation.image

Customizing the toughness of single-network polymer gels independently of their composition and topology remains an unsolved challenge. Traditionally, polymer network toughening is achieved by using specialized monomers or solvents, or by adding secondary networks or fillers that substantially alter composition and may limit applications. Here, we report a new class of force-responsive molecules—tetrafunctional cyclobutanes (TCBs)—that enables the simple synthesis of end-linked gels with nearly identical compositions yet substantially decreased or increased toughness. This behavior is shown to arise from force-coupled chemo- and regio-selective TCB reaction pathways that are dependent on subtle changes in TCB substituents and that dictate bulk gel toughness through a topological descriptor we refer to as network strand continuity. This work introduces tetrafunctional mechanophores and the corresponding concepts of regio- and chemoselective force-coupled reactivity to the field of polymer network mechanochemistry, providing a new design concept for tuning the toughness of simple, commonly used single network gels.

Many virus-like particles (VLPs) have good chemical, thermal, and mechanical stabilities compared to those of other biologics. However, their stability needs to be improved for the commercialization and use in translation of VLP-based materials. We developed an endoskeleton-armored strategy for enhancing VLP stability. Specifically, the VLPs of physalis mottle virus (PhMV) and Q beta were used to demonstrate this concept. We built an internal polymer "backbone" using a maleimide-PEG15-maleimide cross-linker to covalently interlink viral coat proteins inside the capsid cavity, while the native VLPs are held together by only noncovalent bonding between subunits. Endoskeleton-armored VLPs exhibited significantly improved thermal stability (95(degrees)C for 15 min), increased resistance to denaturants (i.e., surfactants, pHs, chemical denaturants, and organic solvents), and enhanced mechanical performance. Single-molecule force spectroscopy demonstrated a 6-fold increase in rupture distance and a 1.9-fold increase in rupture force of endoskeleton-armored PhMV. Overall, this endoskeleton-armored strategy provides more opportunities for the development and applications of materials.

Hydrogen fluoride (HF) is a versatile reagent for material transformation, with applications in self-immolative polymers, remodeled siloxanes, and degradable polymers. The responsive in situ generation of HF in materials therefore holds promise for new classes of adaptive material systems. Here, we report the mechanochemically coupled generation of HF from alkoxy-gem-difluorocyclopropane (gDFC) mechanophores derived from the addition of difluorocarbene to enol ethers. Production of HF involves an initial mechanochemically assisted rearrangement of gDFC mechanophore to α-fluoro allyl ether whose regiochemistry involves preferential migration of fluoride to the alkoxy-substituted carbon, and ab initio steered molecular dynamics simulations reproduce the observed selectivity and offer insights into the mechanism. When the alkoxy gDFC mechanophore is derived from poly(dihydrofuran), the α-fluoro allyl ether undergoes subsequent hydrolysis to generate 1 equiv of HF and cleave the polymer chain. The hydrolysis is accelerated via acid catalysis, leading to self-amplifying HF generation and concomitant polymer degradation. The mechanically generated HF can be used in combination with fluoride indicators to generate an optical response and to degrade polybutadiene with embedded HF-cleavable silyl ethers (11 mol %). The alkoxy-gDFC mechanophore thus provides a mechanically coupled mechanism of releasing HF for polymer remodeling pathways that complements previous thermally driven mechanisms.

The spiropyran mechanophore (SP) is employed as a reporter of molecular tension in a wide range of polymer matrices, but the influence of surrounding environment on the force-coupled kinetics of its ring opening has not been quantified. Here, we report single-molecule force spectroscopy studies of SP ring opening in five solvents that span normalized Reichardt solvent polarity factors (E-T(N)) of 0.1-0.59. Individual multimechanophore polymers were activated under increasing tension at constant 300 nm s(-1) displacement in an atomic force microscope. The extension results in a plateau in the force-extension curve, whose midpoint occurs at a transition force f* that corresponds to the force required to increase the rate constant of SP activation to approximately 30 s(-1). More polar solvents lead to mechanochemical reactions that are easier to trigger; f* decreases across the series of solvents, from a high of 415 +/- 13 pN in toluene to a low of 234 +/- 9 pN in n-butanol. The trend in mechanochemical reactivity is consistent with the developing zwitterionic character on going from SP to the ring-opened merocyanine product. The force dependence of the rate constant (Delta x double dagger) was calculated for all solvent cases and found to increase with E-T(N), which is interpreted to reflect a shift in the transition state to a later and more productlike position. The inferred shift in the transition state position is consistent with a double-well (two-step) reaction potential energy surface, in which the second step is rate determining, and the intermediate is more polar than the product.

Flexible and lightweight sensors can assess their environment for applications that include wearables for health monitoring and soft robotics.

Polymers that release small molecules in response to mechanical force are promising candidates as next-generation on-demand delivery systems. Despite advancements in the development of mechanophores for releasing diverse payloads through careful molecular design, the availability of scaffolds capable of discharging biomedically significant cargos in substantial quantities remains scarce. In this report, we detail a nonscissile mechanophore built from an 8-thiabicyclo[3.2.1]octane 8,8-dioxide (TBO) motif that releases one equivalent of sulfur dioxide (SO2) from each repeat unit. The TBO mechanophore exhibits high thermal stability but is activated mechanochemically using solution ultrasonication in either organic solvent or aqueous media with up to 63% efficiency, equating to 206 molecules of SO2 released per 143.3 kDa chain. We quantified the mechanochemical reactivity of TBO by single-molecule force spectroscopy and resolved its single-event activation. The force-coupled rate constant for TBO opening reaches ∼9.0 s-1 at ∼1520 pN, and each reaction of a single TBO domain releases a stored length of ∼0.68 nm. We investigated the mechanism of TBO activation using ab initio steered molecular dynamic simulations and rationalized the observed stereoselectivity. These comprehensive studies of the TBO mechanophore provide a mechanically coupled mechanism of multi-SO2 release from one polymer chain, facilitating the translation of polymer mechanochemistry to potential biomedical applications.

Second row elements in small- and medium-rings modulate strain. Herein we report the synthesis of two novel oligosilyl-containing cycloalkynes that exhibit angle-strain, as observed by X-ray crystallography. However, the angle-strained sila-cyclooctynes are sluggish participants in cycloadditions with benzyl azide. A distortion-interaction model analysis based on density functional theory calculations was performed.