Browsing by Author "Craig, Stephen L"

Metallosupramolecular polymers are increasingly of interest for functional and degradable polymeric materials. In these materials, the metal-ligand bonds often bear an external mechanical load, but little is yet understood about the nature of mechanically-triggered reactions of metal-ligand bonds and how that reactivity influences the mechanical limits of the material. This dissertation presents a poly(cyclooctene) polymer bearing 2,6-bis(1′-methyl-benzimidazolyl)pyridine (Mebip) ligands on sidechains, which provides easy incorporation into polymer backbones and sidechains, binding to a large variety of metal species, and facile synthesis with sites for future study substituent effects. This platform is employed in proof-of-concept studies comparing the crosslinking behavior of iron(II) trifluoromethanesulfonate and copper(II) trifluoromethanesulfonate. It was found through small molecule spectroscopic studies that both metal species bind in the desired 2:1 MeBip:metal stoichiometry for crosslinking. When these small molecule complexes are polymerized as crosslinkers in gel and solid networks, though the extent of crosslinking is found to be similar, the copper(II)-crosslinked networks exhibited a faster relaxation than the iron(II)-crosslinked networks. Further, under high strains, the copper(II)-crosslinked networks exhibited significantly higher extensibility. This work lays the foundation for further investigations of the effect of metal-ligand bonding on force-coupled properties of materials.

The fracture of polymer networks is usually perceived macroscopically and is considered as a mechanical engineering problem. However, to advance a crack in a polymer network, lots of polymer strands that bridge the crack need to be broken, thus network fracture is molecular as well. In the past 80 years, scientists have been trying to build up quantitative connections between network fracture mechanics and the molecular details of the networks, but to date, there is still no well-accepted quantitative molecular model for network fracture. This is due to the lack of understanding of the molecular details (i.e., strand scission reaction, network topology, etc.) in polymer networks. Developments in polymer mechanochemistry and polymer physics open the door to understanding network fracture from the molecular level. With the concepts of polymer mechanochemistry and polymer physic, this dissertation investigates the correlations between bond/strand scission reaction and the network fracture mechanics theoretically and experimentally.The Lake-Thomas theory is the most well-known molecular theory of network fracture which connects the network critical tearing energy to the scission of polymer strands. Although it has been widely used to explain experimental data, the energy parameter in this theory does not capture the correct chemistry of strand scission and the physics of polymer networks. We provided a conceptual framework to modify the molecular energy parameter in the Lake-Thomas theory by considering the force-coupled reactivity of polymer strand scission reaction (SSR) and network connectivity. First, we consider the strand scission during crack propagation as a mechanochemical reaction of polymer strands, the kinetics of which is dictated by the force on the strands instead of the bond dissociation energy of the repeating monomers. By incorporating the data reported from the single-molecule force spectroscopy experiments, we found the elastic energy stored per bond when typical hydrocarbon polymers break is ca. 60 kJ ∙ mol-1, which is well below the typical carbon-carbon bond dissociation energy (ca. 350 kJ ∙ mol-1). This modification introduced the concept of strand scission reaction into the molecular fracture model of polymer networks and explained the underlying criteria of chain scission. Next, we consider the energy contribution of unbroken strands in the polymer networks during crack propagation. This modification includes not only the energy stored in the breaking network strands (bridging strands) but also the energy stored in the tree-like structure of the strands connecting the bridging strands to the network continuum, which remain intact as the crack propagates. We show that the tearing energy stored in each of the generations of this tree depends non-monotonically on the generation index due to the nonlinear elasticity of the stretched network strands. We further show that the energy required to break a single bridging strand is not necessarily dominated by the energy stored in the bridging strand itself but in the higher generations of the tree. To verify our theoretical modification of the Lake-Thomas theory, we designed and synthesized covalent polymer gels in which the macroscopic fracture “reaction” is controlled by mechanophores embedded within mechanically active network strands. The gels were prepared through the end-linking of azide-terminated tetra-arm PEG (Mn = 5 kDa) with different bis-alkyne linkers under identical conditions, except that the bis-alkyne was varied to include either a cis-diaryl or cis-dialkyl linked cyclobutane mechanophore that acts as a mechanochemical “weak link” through a force-coupled cycloreversion. A control network featuring a bis-alkyne without cyclobutane (non-mechanophore) was also synthesized. The networks show the same small strain elasticity and swelling, but they exhibit tearing energies that span a factor of 8 (3.4, 10.6, and 27.1 J ∙ m-2 for networks with cis-diaryl, cis-dialkyl cyclobutane mechanophores, and non-mechanophore control, respectively). The difference in fracture energy is well-aligned with the force-coupled scission kinetics of the mechanophores observed in single-molecule force spectroscopy (SMFS) experiments, implicating local resonance stabilization of a diradical transition state in the cycloreversion of cis-diaryl cyclobutane mechanophore as a key determinant of the relative ease with which its network is torn. The connection between macroscopic fracture and a small-molecule reaction mechanism suggests that the fracture of polymer networks is a chemical reaction. Further characterizations of the force-coupled kinetics of cis-diaryl and cis-dialkyl cyclobutane mechanophores with SMFS suggest opportunities for constructing quantitative correlations between strand scission reaction and network fracture mechanics. Although the tearing energy of polymer networks is highly dependent on the strand scission reaction of network strands, how the networks with mixed strand scission reactions behave remains unclear. Hence, the impact of mixed strand scission reaction is studied through the synthesis of networks with varied ratios of cis-diaryl cyclobutane mechanophore (“weak”) and non-mechanophore (“strong”) control linkers. The strands with mechanophore linkers are about 4 ~ 5 times weaker than the strands with non-mechanophore linkers according to SMFS experiments. Tearing energy versus strong linkers percentage demonstrate the existence of plateau regions for < 40% strong linker at 2 ~ 3 J∙m-2 and >75% strong linker at ~20 J∙m-2. These regions correspond somewhat closely to the expected Flory-Stockmayer percolation thresholds for a tetra-functional network, pc (strong) = 0.67 and pc (weak) = 0.33. From the classical point of view (e.g., Lake-Thomas theory), the crack propagation is usually assumed to be path-determined instead of reactivity-determined. These data suggest the path-determined mechanism, which predicts that the tearing energy should vary linearly with the average strength of the bonds, does not correctly capture the trend in tearing energy, and the reactivity-determined mechanism is likely to be correct. Ongoing experiments on the actual percolation threshold of either weak or strong chains in the networks would provide more understanding of the reactivity-determined mechanism. Our current work on end-linked networks suggests that the network is weak with incorporated weak mechanophores. However, incorporating weak mechanophores as crosslinkers in radically polymerized networks yields an opposite result: the network is tougher with incorporated weak mechanophores. A cis-diaryl cyclobutane-mechanophore is developed as a mechanochemically weak covalent crosslinker and incorporated into controlled radical-polymerized networks. The networks consist of crosslinkers that are mechanochemical weak and long primary chains that are mechanochemically strong. The activation force of the covalent crosslinker is estimated to be ca. 5 times weaker than the corresponding control crosslinkers and the polymer backbone bonds. However, the networks made from the weak crosslinkers are 2 ~ 9 times tougher than the networks made from the corresponding control crosslinkers (non-mechanophore) while the former exhibit the same small strain elasticity as the latter. By altering the degree of polymerization (DP) of primary chains while keeping the crosslinking density similar, we found that, with primary chains that have DP ≈ 1300 and larger, the networks made from the weak crosslinkers are 6 ~ 9 times tougher than that made from control crosslinkers. With primary chains that have DP ≈ 300, the tearing energies of these two types of networks have no significant difference. This suggests that having long enough primary chains is critical for the toughening effect. The underlying principles of this toughening effect are the weak crosslinkers can be activated before the primary chain breaks, and the inherent topological loopy structures of the network can be released as “stored-length”. Such change in topological structures of the networks after weak crosslinker activation can redistribute the load and toughen the networks.

Just as heat, light and electricity do, mechanical forces can also stimulate reactions. Conventionally, these processes - known as mechanochemistry - were viewed as comprising only destructive events, such as bond scission and material failure. Recently, Moore and coworkers demonstrated that the incorporation of mechanophores, i.e., mechanochemically active moieties, can bring new types of chemistry. This demonstration has inspired a series of fruitful works, at both the molecular and material levels, in both theoretical and experimental aspects, for both fundamental research and applications. This dissertation evaluates mechanochemical behavior in all of these contexts.

At the level of fundamental reactivity, forbidden reactions, such as those that violate orbital symmetry effects as captured in the Woodward-Hoffman rules, remain an ongoing challenge for experimental characterization, because when the competing allowed pathway is available, the reactions are intrinsically difficult to trigger. Recent developments in covalent mechanochemistry have opened the door to activating otherwise inaccessible reactions. This dissertation describes the first real-time observation and quantified measurement of four mechanically activated forbidden reactions. The results provide the experimental benchmarks for mechanically induced forbidden reactions, including those that violate the Woodward-Hoffmann and Woodward-Hoffmann-DePuy rules, and in some cases suggest revisions to prior computational predictions. The single-molecule measurement also captured competing reactions between isomerization and bimolecular reaction, which to the best of our knowledge, is the first time that competing reactions are probed by force spectroscopy.

Most characterization for mechanochemistry has been focused on the reactivity of mechanophores, and investigations of the force coupling efficiency are much less reported. We discovered that the stereochemistry of a non-reactive alkene pendant to a reacting mechanophore has a dramatic effect on the magnitude of the force required to trigger reactivity on a given timescale (here, a 400 pN difference for reactivity on the timescale of 100 ms). The stereochemical perturbation has essentially no measurable effect on the force-free reactivity, providing an almost perfectly orthogonal handle for tuning mechanochemical reactivity independently of intrinsic reactivity.

Mechanochemical coupling is also applied here to the study of reaction dynamics. 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. The 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, as compared to 19 out of 400 such events in molecular dynamics simulations.

On the materials level, the inevitable stress in materials during usage causes bond breakage, materials aging and failure. A strategy for solving this problem is to learn from biological materials, which are capable to remodel and become stronger in response to the otherwise destructive forces. Benzocyclobutene has been demonstrated to mechanically active to ortho-quinodimethide, an intermediate capable for [4+4] dimerization and [4+2] cycloaddition. These features make it an excellent candidate for and synthesis of mechanochemical remodeling. A polymer containing hundreds of benzocyclobutene on the backbone was synthesized. When the polymer was exposed to otherwise destructive shear forces generated by pulsed ultrasound, its molecular weight increased as oppose to other mechanophore-containing polymers. When a solution of the polymer with bismaleimide was subjected to pulsed ultrasonication, crosslink occurred and the modulus increased by two orders of magnitude.

Mechanically induced chemical bond scission underlies the fracture and macroscopic failure of polymeric materials. Thus, the mechanical strength of scissile chemical bonds plays a role in material failure and in the mechanical initiation of cascade reactions, but quantitative measurements of mechanical strength are rare. This dissertation describes research that quantifies relative mechanical strengths of polymers that possess a variety of chemical and topological functionalities in order to assess the strength of putative "weak bonds" along their backbones.

First, relative mechanical strengths of "weak" bonds that break by homolytic scission were assessed: the carbon-nitrogen bond of an azobisdialkylnitrile (< 30 kcal mol-1), the sulfur-sulfur bond of a disulfide (54 kcal mol-1), and the carbon-oxygen bond of a benzylphenyl ether (52-54 kcal mol-1). The mechanical strengths were assessed in the context of chain scission triggered by pulsed sonication of polymer solutions, by using the competing non-scissile mechanochemical reaction of gem dichlorocyclopropane mechanophores as a gauge of the force required for chain scission. The relative mechanical strengths of the three weak bonds are found to be: azobisdialkylnitrile (weakest) < disulfide < benzylphenyl ether. The greater mechanical strength of the benzylphenyl ether relative to the disulfide is ascribed in part to poor mechanochemical coupling as a result of the rehybridization that accompanies carbon-oxygen bond scission.

Studies of bond scission were extended to include the effect of topology. The introduction of mechanical bonding in polymers can sufficiently affect physical properties, but experimental measurements of the relative strengths of topological bonding are rare. We studied the relative mechanical strengths of three bonding topologies formed from the same set of chemical functionalities: a catenane, a symmetrical macrocycle, and a linear construct. Mechanical strengths were obtained by analysis of molecular weight of polymers with embedded topological molecules after 4 h of pulsed sonication (M4h). The obtained M4h was converted to the length (L4h) using the calculated force free length of each monomer. The relative mechanical strengths of these topological molecules are nearly identical based on L4h, and we conclude that the mechanical strength of a mechanical bond (catenane) is as high as that of a linear analog.

Using these methods, the relative mechanical strengths of triazoles were also investigated. Random copolymers containing either 1,4-triazole, 1,5-triazole, or indole were synthesized via entropy driven ring opening metathesis co-polymerization. Solutions of those polymers were subjected to pulsed ultrasound for 4 hours and M4h measured was less than the M4h of poly(gDCC). Taken together, these results suggest that the introduction of these heterocycles does weaken the polymer main chain, but not through mechanically assisted cycloreversion.

As an extended study of mechanical strength of different molecular topologies, the sonochemistry of a polymeric trefoil knot was also investigated. A zinc-templated polymeric trefoil knot was subjected to pulsed ultrasound, to determine whether demetallation can be mechanically triggered by tightening the trefoil knot under high forces of tension. The products of sonication of the polymeric trefoil knot were analyzed by 1H NMR and by the color change of dithizone solution used to coordinate any released zinc. No evidence for mechanical demetallation or knot scission was obtained, suggesting that the presence of the zinc template in the trefoil knot can prevent knot tightening and subsequent weakening and scission.

Melanin is a ubiquitous biological pigment found in bacteria, fungi, plants, and animals. It has a diverse range of ecological and biochemical functions including display, evasion, photoprotection, detoxification, and metal scavenging. Two forms of melanin produced from different molecular precursors are present in nature - eumelanin (dark brown-black in color) and pheomelanin (orange-red in color). Both eumelanin and pheomelanin are complex highly cross-linked biopolymers that are found intertwined with proteins, lipids, and metal ions in nature.

Recent reports have used morphological evidence to suggest the presence of melanin in the fossil record. These studies have been met with criticism due to their lack of chemical evidence to support melanin identification. This dissertation describes chemical approaches to unambiguously verify the presence of melanin in the fossil record and characterize the ancient pigment. It also explores the limitations for the survival of melanin in the fossil record and the possibility that melanin acts as a protective matrix to preserve other biomolecules that are embedded in the pigment.

Melanin has unique chemical signatures that are commonly used to characterize and compare the pigment of modern organisms. We applied these chemical approaches to the study of fossil pigmentation. Analysis of the black pigmentation of two > 160 million year old (Mya) Jurassic cephalopod ink sacs provided the first conclusive evidence for eumelanin in the fossil record. The preserved fossil eumelanin was then compared to modern cephalopod eumelanin from Sepia officinalis. Using these chemical approaches we found that fossil eumelanin was chemically and morphologically identical to S. officinalis eumelanin.

Although there is mounting chemical evidence for the presence and preservation of melanin in the fossil record, there is very little data constraining its long-term survival. We applied the analytical approaches designed to study fossil melanins and techniques used to study fossil sediments to compare the fossil inks from three deposits of similar age and lithology, but different maturation histories. Specifically, two ~ 180 Mya fossil ink sacs from a site that has entered the oil window in Holzmaden, Germany were compared to the previously analyzed fossil inks from two less mature sites in southern England. The chemistry of eumelanin was shown to alter at the onset of the oil window regardless of the age of the specimen. The decrease in surviving melanin was accompanied by an increase in the relative abundance of organic macromolecular material (kerogen), but no consistent change in melanin morphology.

Finally, the role of melanin as a matrix that enhances the preservation of other biomolecules in the fossil record was considered. Proteins, commonly associated with melanin in modern organisms, were discovered in the aforementioned fossil ink sacs during full-scale chemical analysis. The amino acid profile of the protein in each fossil specimen was determined with an amino acid analyzer and compared to the amino acid profile the protein in modern S. officinalis. Statistical analysis of the amino acid distributions indicated that there is no significant difference between the amino acid profile of modern and fossil melanins. In order to verify the ancient origin of the amino acids in the fossil ink sacs, the ratio of D/L amino acid isomers was determined. While the proteins of living organisms consist of only L-amino acids, post-mortem the amino acids slowly convert from L to D form until they reach equilibrium (D/L = 1). This process is called racemization. The amino acids in the fossil ink sacs were racemized, which suggests their ancient origin. This marks the oldest determination of protein in a fossil system and provides evidence that the longevity of proteins may be enhanced when associated with melanin.

When mechanical force is applied to synthetic materials, polymer chains become

highly strained, leading to bond scission and ultimately material failure. Over the last

decade or so, work in the field of polymer mechanochemistry has coupled this tension to

desired covalent chemical reactions. These functionalities, known as mechanophores,

react to unveil a new molecular structure and triggering a constructive response. This

strategy has been explored for a variety of purposes, including stress sensing, stress

strengthening, small molecule release, catalysis, and development of soft devices.

Additionally, the effect of force on a reaction coordinate, through biasing and probing

reaction pathways and trapping of transition states and intermediates, has been well–

studied experimentally and in theory. This work reports on understanding structure property

relationships for the spiropryan mechanophore and expanding our control of mechanochromism

from the single-molecule to device scale.

First, we report the effect of substituents on spiropyran derivatives substituted

with H, Br, or NO2 para to the breaking spirocyclic C− O bond using single molecule

force spectroscopy. 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 dependenc

eon 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.

The development and characterization of new force probes has enabled

additional, quantitative studies of force-coupled molecular behavior in polymeric

materials. The relationship between strain and color change has been measured for

these three spiropyran derivatives. The color appears at around the same strain and the

ratio of color intensities remains constant for all three derivatives. This result was not predicted by

previously reported computational work and motivates future studies of

force distribution within filled silicones.

On the material and device scale, we have utilized mechanochromism for soft

and stretchable electronics, which are promising for a variety of applications such as

wearable electronics, human− machine interfaces, and soft robotics. These devices,

which are often encased in elastomeric materials, maintain or adjust their functionality

during deformation, but can fail catastrophically if extended too far. Here, we report

new functional composites in which stretchable electronic properties are coupled to

molecular mechanochromic function, enabling at-a-glance visual cues that inform user

control. These properties are realized by covalently incorporating a spiropyran

mechanophore within poly(dimethylsiloxane) to indicate with a visible color change that

a strain threshold has been reached. The resulting colorimetric elastomers can be molded

and patterned so that, for example, the word “STOP” appears when a critical strain is

reached, indicating to the user that further strain risks device failure. We also show that

the strain at color onset can be programmed through the layering of silicones with

different moduli into a composite. As a demonstration, we show how color onset can be

tailored to indicate a when a specified frequency of a stretchable liquid metal antenna

has been reached. The multi-scale combination of mechanochromism and soft

electronics offers a new avenue to empower user control of strain-dependent properties

for future stretchable devices.

Through the study of the reaction that converts spiropyran into merocyanine, we

are able to teach and connect a number of standard general chemistry course topics

while also introducing students to polymer concepts. By framing a number of different

concepts including molecular orbital theory, quantum mechanics, equilibrium,

hydrogen bonding, mechanical work, and polymer chemistry with the same reaction,

our goal is to allow students to see connections in seemingly disparate sections of

general chemistry.

The reactivity of a mechanically active functional group is determined by the

activation energy of the reaction (ΔG‡) and the force-coupled change in length as the

reaction proceeds from the ground to transition state (Δx‡). Finally, we report a combination

of both principles enhances the mechanochemical reactivity of epoxides:

placing alkenes adjacent to cis-epoxide mechanophores along a polymer backbone

results in ring-opening to carbonyl ylides during sonication, whereas epoxides lacking

an adjacent alkene do not. Upon release, tension-trapped ylides preferentially close to

their trans-epoxides in accordance with the Woodward-Hoffman rules. The reactivity of

carbonyl ylides is exploited to tag the activated species with spectroscopic labels for

force-induced cross-linking through a reaction with pendant alcohols. Even with alkene

assistance, mechanochemical reactivity remains low; single molecule force spectroscopy

establishes a lower limit for ring-opening ca. 1 sec-1 at forces of ~2600 pN.

The development of multi-mechanophore polymers (MMPs) has empowered new methodologies for observing and quantifying mechanochemical transformations. Previously developed techniques such as single-molecule force spectroscopy (SMFS) and pulsed ultrasound can be used to induce and observe up to hundreds of chemical reactions within a single polymer, enabling mechanistic insights into mechanochemical reactivity. The bulk of the work presented herein (Chapters 2-5) involves the use of these techniques to elucidate substituent effects on the covalent mechanochemistry of four-membered carbocycles, namely the force-triggered ring-opening reactions of fused-cyclobutane (CB) and cyclobutene (CBE) mechanophores.

MMPs that contain multiple CB and CBE repeats are typically synthesized via entropy-driven ring-opening metathesis polymerization (ED-ROMP, Chapters 3-5), a technique used widely in the field of polymer mechanochemistry. While useful for generating polymers for fundamental mechanistic investigations, there are several challenges inherent to the ED-ROMP approach that limit its impact and applicability (covered in Chapter 1). We therefore sought to overcome some of these challenges by introducing a new class of mechanophore monomers that are amenable to free-radical addition polymerization. In Chapter 2 we report that cyclobutene carboxylates that are fused to larger rings are amenable to controlled radical polymerization techniques, specifically reversible addition-fragmentation chain transfer (RAFT) copolymerization with butyl acrylate. The fused ring repeats act as stored-length mechanophores along the polymer backbone, and so these polymers are a rare example of high mechanophore content polymers formed by addition polymerization. Analysis of mechanophore activation as a function of polymer scission cycle reveals that these CB-based mechanophores operate in high force regimes. In addition, the kinetics and “controllability” of the RAFT polymerizations are investigated as a function of (co)monomer composition, providing a foundation for the design of bulk polymer networks that contain a tunable amount of these stored-length mechanophores.

In Chapter 3 we report the force-dependent kinetics of stored length release in a family of covalent domain polymers based on cis-1,2-substituted CB mechanophores, which have the potential to serve as covalent synthetic mimics of the mechanical unfolding of noncovalent “stored length” domains in structural proteins. The stored length is determined by the size (n) of a fused ring in an [n.2.0] bicyclic architecture, and it can be made sufficiently large (> 3 nm per event) that individual unravelling events are resolved in both constant-velocity and constant-force SMFS experiments. Replacing a methylene in the pulling attachment with a phenyl group drops the force necessary to achieve rate constants of 1 s-1 from ca. 1970 pN (dialkyl handles) to 630 pN (diaryl handles), and the substituent effect is attributed to a combination of electronic stabilization and mechanical leverage effects. In contrast, the kinetics are negligibly perturbed by changes in the amount of stored length. The independent control over unravelling force and extension holds promise as a probe of molecular behavior in polymer networks and for optimizing the behaviors of materials made from covalent domain polymers.

In Chapter 4 we use a combination of SMFS and computation to gain a fundamental understanding of substituent effects on a different class of force-triggered reactions: the forbidden disrotatory ring-opening reaction of CBE mechanophores. We synthesized a series of cis-ester-substituted CBE mechanophores that probed the effects of substituents attached to the breaking sigma bond and the nascent π bond. In general, we found that substituents connected to the breaking sigma bond had a larger influence on reaction kinetics. Computations reveal that the extent of mechanical coupling is similar between all derivatives studied, so we explain the observed differences (or lack thereof) in reactivity by examining the degree to which the substituents provide electronic stabilization to the TS, which has substantial diradical character. We find that an alkyne substituent connected to the breaking sigma bond provides the most stabilization. In addition, the alkyne is initially insulated from the nascent π bond of CBE, but extends the conjugation of the unveiled butadiene product enough to make it fluorescent, providing a foundation for CBEs to become a class of “turn-on” mechanofluorophores.

We combine our insights from Chapters 3-4 to better understand a new monomer presented in Chapter 5 that uses the photoswitching chemistry of a diarylethene (DAE) substituent to photochemically switch the mechanophore between cyclobutene-like and cyclobutane-like structures. Quantitative results derived from SMFS experiments reveal that the photochemical trigger can alter the reaction rate of the monomer by > 105 at a force of 810 pN (the CB-like monomer being easier to activate). We therefore have designed a polymer system whereby the mechanochemical reactivity of the polymer backbone can be regulated (sped up or slowed down) by a separate photochemical reaction. Interestingly, results from sonication studies reveal that despite their disparate reactivates, the two DAE isomers yield the same mechanochemical product. The mechanistic insights gleaned from these results will serve as a foundation for the future molecular-level design of similar, photoswitchable mechanophores.

Covalent polymer mechanochemistry has attracted significant attention in the last decade due to its broad potential in stress-responsive materials. Force-sensitive chemical moieties (mechanophores) embedded into polymer backbones are triggered by mechanical loads, with demonstrated responses that include mechanochromism, small-molecule release, mechano-catalysis, enhancements in material toughness and even electrical conductivity. While many qualitative studies have demonstrated the structure-activity correlation between mechanophore designs and the force-responsive properties of bulk materials, quantitative investigations remain rare. Gaining quantitative perspectives is advantageous for the rational, molecular design of polymer materials with tailored mechanical properties, which ultimately could lead to cost-effective and less wasteful materials. Here, we probe quantitative structure-activity relationships on three fronts: 1) stereochemical effects in the mechanochemical reactivity of endo- vs. exo- furan-maleimide Diels-Alder adducts; 2) the mechanochemical reaction pathways of dichlorocyclopropane diester ring opening reaction; 3) enhanced mechanics of hydrogels through stress-responsive covalent extension of single strands within the polymer network. Chapter 2 presents a systematic study of a structure-activity correlation in polymer mechanochemistry, specifically investigating how stereoisomerism affects the mechanochemical scission of furan-maleimide Diels-Alder adducts. In this study, we evaluated the internal competition between the mechanically triggered retro-DA reaction and the mechanochemical ring opening of gem-dichlorocyclopropane (gDCC) mechanophores in the pulsed sonication of polymer solutions. The relative extent of the two mechanochemical reactions in the same polymer shows that the endo DA isomer exhibits greater mechanical lability than its exo isomer. This result contrasts with recent measurements of the relative rates of scission in a similar system and points to potential enhanced sensitivity obtained through the use of internal competition as opposed to absolute rates in assessing mechanical reactivity in sonication studies. Chapter 3 investigates how the mechanically accelerated ring opening of gDCC mechanophores is influenced by the use of ester, rather than alkyl, handles. We find that when ester groups are used to link the mechanophore to the attached polymer chains, both cis- and trans- gDCC pulling lead to reaction rates and outcomes that are consistent with the symmetry-allowed disrotatory pathways at forces relevant to either single-molecule force spectroscopy and sonication experiments. Finally, Chapter 4 presents a quantitative study of how the properties of a bulk materials can be enhanced by embedding mechanophores capable of covalent reactive strand extension (RSE) into the constituent strands of a polymer network. RSE allows constituent strands to lengthen through force-coupled reactions that are triggered as the strands reach their nominal breaking point. Reactive strand extensions of up to 40% lead to hydrogels that stretch 40-50% further than, and exhibit tear energies twice that of, networks made from analogous control strands. The enhancements are synergistic with those provided by double network architectures, and complement other existing toughening strategies.

The addition of mechanically active functional groups (mechanophores) to polymer scaffolds has resulted in new chemical transformations and materials properties. The novel functions in these polymers are achieved in response to a universal input: mechanical force. This dissertation describes studies that expand our ability to elicit and modify chemical reactivity through the application of force (mechanochemistry), both through fundamental studies of mechanochemical coupling and through the synthesis and characterization of new mechanophores.

In order to probe mechanochemical coupling, single molecule force spectroscopy was used to directly quantify and compare the forces associated with the ring opening of gem-dibromo and gem-dichlorocyclopropanes (gDBCs and gDCCs) affixed along the backbone of cis-polynorbornene (PNB) and cis-polybutadiene (PB). At a tip velocity of 0.3 μ sec-1, the isomerization of gDBC-PNB, gDCC-PNB, gDBC-PB, and gDCC-PB to their respective 2,3-dihaloalkenes occurs at 740, 900, 1210 and 1330 pN, respectively. In contrast to their relative importance in determining the rates of the thermal gDHC ring openings, the polymer backbone has much greater impact on gDHC mechanochemistry than does the halogen. The root of the effect lies in more efficient chemomechanical coupling through the PNB backbone, which acts as a phenomenological lever with greater mechanical advantage than the PB backbone. The ability to affect the reactivity of a mechanophore by polymer backbone manipulation provides a previously underappreciated means to tailor mechanochemical response. The experimental results are supported computationally and provide the foundation for a new strategy by which to engineer mechanical reactivity.

The ability to increase the reactivity of mechanophores by changing their polymer scaffold can lead to the realization of mechanically-induced transformations that were otherwise inaccessible. To probe this increased mechanophore reactivity, epoxidized polybutadiene and epoxidized polynorbornene were subjected to pulsed ultrasound in the presence of small molecules capable of being trapped by carbonyl ylides. When epoxidized polybutadiene was sonicated, there was no observable small molecule addition to the polymer. Concurrently, no appreciable isomerization (cis to trans epoxide) was observed, indicating that the epoxide rings along the backbone are not mechanically active under the experimental conditions employed. In contrast, when epoxidized polynorbornene was subjected to the same conditions, both addition of ylide trapping reagents and net isomerization of cis to trans epoxide were observed. The results demonstrate the mechanical activity of epoxides, show that mechanophore activity is determined not only by the functional group but also the polymer backbone in which it is embedded, and facilitate a characterization of the reactivity of the ring opened dialkyl epoxide.

Commercially available fluorinated polymers were also investigated as previously unrealized mechanophore-bearing polymers and as candidates for thermally re-mendable materials by examining their response to applied stress. Perfluorocyclobutane (PFCB) polymer solutions were subjected to pulsed ultrasound, leading to mechanically induced chain scission and molecular weight degradation. 19F NMR revealed that the new, mechanically generated end groups are trifluorovinyl ethers formed by cycloreversion of the PFCB groups- a process that differs from thermal degradation pathways. One consequence of the mechanochemical process is that the trifluorovinyl ether end groups can be re-mended simply by subjecting the polymer solution to the original polymerization conditions, i.e., heating to >150 °C. Stereochemical changes in the PFCBs, in combination with radical trapping experiments, indicate that PFCB scission proceeds via a stepwise mechanism with a 1,4-diradical intermediate, offering a potential mechanism for localized functionalization and cross-linking in regions of high stress.

The acceleration of chemical reactions under mechanical stress has been known since the earliest days of polymer science. Once limited to the simple scission of polymer chains, mechanical force can now be used to produce a wide array of productive chemistry. The development of so-called "covalent mechanochemistry," has allowed chemists to challenge and support classically held models of chemical reactivity, impacting both synthetic chemistry and material science. This work aims to develop molecular tools that respond to stress and explore the mechanisms behind that response. While a wide-range of fields may be impacted, the overall inspiration for the work herein is the development of materials with rich and robust molecular responses to otherwise destructive forces. To this end we focus on: (a) developing new mechanochemically reactive organic molecules (mechanophores) that undergo constructive covalent transformations in linear polymers under stress; (b) probing the nature of force transduction across length scales, from bulk (macroscopic) to microscopic stress, in networks thus informing material design; (c) constructing systems that reversibly amplify mechanochemical signals via catalysis.

Force induced transformations of polymer bound mechanophores have the potential to produce a rich array of stress responsive behavior. One area of interest is the activation of non-scissile mechanophores in which latent reactivity can be unveiled. Under the appropriate conditions, this new reactivity could lead to constructive bond formation, and potentially a pathway to mechanochemical stress strengthening. In chapter 2, the mechanical activation of a bicyclo[3.2.0]heptane (BCH) mechanophore is demonstrated via selective labeling of bis-enone products. BCH ring-opening, via a formal [2+2] cycloreversion, produces large local elongation (> 4 Å) and products that are reactive to Michael-type additions under mild conditions. Subsequent photocyclization regenerates the initial BCH functionality, providing switchable structure and reactivity along the polymer backbone in response to stress and visible light.

In chapter 3, the [2+2] cycloreversion of cyclobutane mechanophores is further explored through the development of bicyclo[4.2.0]octane (BCO) mechanophores. Using carbodiimide polyesterification, BCO units were incorporated into high molecular weight polymers containing up to 700 mechanophores per polymer chain. Under exposure to the otherwise destructive elongational forces of pulsed ultrasound, these mechanophores unravel by ~7 Å per monomer unit to form unsaturated esters that react constructively via nucleophilic thiol-ene conjugate addition to form sulfide functionalized copolymers and cross-linked polymer networks. The wide variety of possible product stereochemistry provided an opportunity to probe the dynamics of the mechanochemical ring opening. A series of bicyclo[4.2.0]octane derivatives that varied in stereochemistry, substitution, and symmetry were synthesized and activated. Product stereochemistry was analyzed by conventional NMR and chromatographic means, which enabled inquiry into the mechanism of the mechanochemical [2+2] cycloreversion. These results support that the ring opening is not concerted, but proceeds via a 1,4 diradical intermediate. Additionally, insight is provided into the 1,4-diradical dynamics prior to product formation.

We next turn our attention to the molecular level responses of polymer materials under macroscopic stress. Hydrogels and organogels made from polymer networks are widely used in biomedical applications and soft, active devices for which the ability to sustain large deformations is required. The strain at which polymer networks fracture is typically improved through the addition of elements that dissipate energy, often strong, yet reversible interactions. The result is often tougher materials, resulting from both greater nominal strains and elastic moduli. These materials require extra work to achieve a desired level of deformation, however, there is little evidence that large amounts of energy dissipation is required to achieve greater nominal strains. In chapter 4, we show that the addition of mechanically "invisible" supramolecular crosslinks causes substantial increases in the ultimate gel properties without incurring the added energetic costs of dissipation. We then incorporated a chemiluminescent stress-sensor, the bis(adamantyl)dioxetane covalent cross-linker, first developed in the Sijbesma group, which emits light in the event of covalent bond scission. In these experiments we demonstrate that the occurrence of macroscopic failure (from stress-strain curves) coincides with the molecular level failure of the underlying covalent network.

Finally, in chapter 5, we turn our attention to the development of mechanocatalytic systems. By activating or otherwise altering the activity of a catalyst using force, a single mechanochemical event may be amplified (i.e. by catalyst turnover). Such systems have been previously reported in the form of force-activated polymer bound transition metal complexes. Beyond these on/off systems, we imagine that force may be used to tune catalyst selectivity, via the perturbation of ligand geometry. Here, we report a catalyst that couples a photoswitch to the biaryl backbone of a chiral bis(phosphine) ligand, thus allowing photochemical manipulation of ligand geometry without significantly altering the electronic structure. The changes in catalyst activity and selectivity upon switching can be attributed to intramolecular mechanical forces, laying the foundation for a new class of catalysts whose selectivity can be varied smoothly and in situ over a useful range by controlling molecular stress experienced by the catalyst during turnover. Forces on the order of 100 pN are generated, leading to measureable changes in the enantioselectivities of asymmetric Heck arylations and Trost allylic alkylations.

The key concept of polymer mechanochemistry is the rational design of mechanophores. When incorporated into polymeric materials, mechanophores can be used to produce strain-dependent covalent chemical responses, including stress-strengthening, stress-sensing and network remodeling. In general, it is desirable for mechanophores to be highly inert in the absence of force but highly reactive when under applied tension. We show that the Fe−Cp bond in ferrocene is the preferential site of mechanochemical scission in the pulsed ultrasonication of main-chain ferrocene-containing polybutadiene-like polymers. Quantitative studies reveal that the Fe−Cp bond is similar in strength to the carbon−nitrogen bond of an azobisdialkylnitrile (bond dissociation energy < 30 kcal/mol), despite the significantly higher Fe-Cp bond dissociation energy (up to 90 kcal/mol). Mechanistic studies are consistent with a predominately heterolytic mechanism of chain scission. DFT calculations provide insights into the origins of ferrocene’s mechanical lability.

The unexpected combination of force-free stability and mechanochemical activity for ferrocene raises the tantalizing question as to whether similar mechanochemical activity might be present in other metallocenes, and, if so, what features of metallocenes dictate their relative ability to act as mechanophores. We find that ruthenocene, in analogy to ferrocene, acts as a highly selective site of main chain scission despite the fact that it is even more inert. A comparison of ruthenocene and ferrocene reactivity provides insights as to the possible origins of metallocene mechanochemistry, including the relative importance of structural and thermodynamic parameters such as bond length and bond dissociation energy. These results suggest that metallocenes might be privileged mechanophores through which highly inert coordination complexes can be made dynamic in a stimuli-responsive fashion, offering potential opportunities in dynamic metallo-supramolecular materials and in mechanochemical routes to reactive intermediates that are otherwise difficult to obtain.

To further elucidate the mechanistic factors that dictate the mechanochemical activity of metallocenes, we used single molecule force spectroscopy to probe the mechanical reactivity of a series of ferrocenophanes. The force-coupled rate of cyclopentadiene (Cp) dissociation among various ferrocene derivatives varies by several orders of magnitude at ~1 nN, and the differences in reactivity are not correlated with ring strain in the reactants. Instead, a strong correlation with the extent of rotational realignment of the two Cp ligands is observed. Mechanophores with pulling points that are conformationally restricted by distal attachments to an eclipsing orientation are most labile, whereas conformationally unrestricted ligands reorient under force to effectively superpose “catch bond” like contributions onto the overall mechanically assisted dissociation reaction. The ability to program the mechanism of ferrocene dissociation to proceed through ligand “peeling”, as opposed to the more conventional “shearing” mechanism of the parent ferrocene, leads to enhanced macroscopic, multi-responsive behavior including mechanochromism and force-induced crosslinking in ferrocenophane-containing polymers.

Stress sensing at the molecular level in elastomer-based composites is crucial as it could prevent catastrophic material failure from early on and prolong its lifetime. The emerging field of polymer mechanochemistry provides such opportunity by incorporating force probes into the polymer network to generate stress-induced spectroscopic responses. Force probes that could offer irreversible responses when activated is ideal for easy characterization. Here, we designed a coumarin dimer mechanophore that could be covalently embedded into a polymer main chain. Its mechanochemical lability is quantified by competing internally with the ring opening of gem-dichlorocyclopropane (gDCC) and revealed to be comparable to a disulfide bond. The structure-reactivity relationship of coumarin dimer derivatives is investigated to show that the force sensitivity could be tuned by manipulating the force-free activation energy and mechanical coupling, which is further validated by computational modeling. Further, different coumarin dimer derivatives were embedded into the main chain and filler-matrix interface in a particle-filled rubber. The relative activation at these positions under a compressive loading was quantified and revealed that the stress-concentration effect at the heterointerface could result in one order of magnitude higher activation ratio compared to the polymer main chain.

Transforming growth factor beta (TGF-beta) is an important cytokine responsible for a wide range of different cellular functions including extracellular matrix formation, angiogenesis and epithelial-mesenchymal transition. We have sought to use self-assembling DNA nanostructures to influence TGF-beta signaling.

The predictable Watson Crick base pairing allows for designing selfassembling nanoscale structures using oligonucleotides. We have used the method of DNA origami to assemble structures functionalized with multiple peptides that bind TGF-beta receptors outside the ligand binding domain. This allows the nanostructures to cluster TGF-beta receptors and lower the energy barrier of ligand binding thus sensitizing the cells to TGF-beta stimulation. To prove efficacy of our nanostructures we have utilized immunofluorescent staining of Smad2/4 in order to monitor TGF-beta mediated translocation of Smad2/4 to the cell nucleus. We have also utilized Smad2/4 responsive luminescence constructs that allows us to quantify TGF-beta stimulation with and without nanostructures.

To functionalize our nanostructures we relied on biotin-streptavidin linkages. This introduces a multivalency that is not necessarily desirable in all designs. Therefore we have investigated alternative means of functionalization.

The first approach is based on targeting DNA nanostructure by using zinc finger binding proteins. Efficacy of zinc finger binding proteins was assayed by the use of enzyme-linked immunosorbent (ELISA) assay and atomic force microscopy (AFM). While ELISA indicated a relative specificity of zinc finger proteins for target DNA sequences AFM showed a high degree of non-specific binding and insufficient affinity.

The second approach is based on using peptide nucleic acid (PNA) incorporated in the nanostructure through base pairing. PNA is a synthetic DNA analog consisting of a backbone of repeating N-(2-aminoethyl)-glycine units to which purine and pyrimidine bases are linked by amide bonds. The solid phase synthesis of PNA allows for convenient extension of the backbone into a peptide segment enabling peptide functionalization of DNA nanostructures. We have investigated how the neutral character of PNA alters the incorporation in DNA based nanostructures compared to a DNA control using biotinylation and AFM.

Results indicate that PNA can successfully be used as a way of functionalizing DNA nanostructures. Additionally we have shown that functionalized nanostructures are capable of sensitizing cells to TGF-beta stimulation.

Mechanical forces are known to drive a range of covalent chemical reactions and have a number of applications, including access to new reaction pathways, polymer transformations, degradable polymers, stress/strain sensing in bulk materials, and the release of small molecules/protons. In switchable catalysis, mechanical forces have been mainly exploited to activate latent catalysts by unplugging inhibiting ligands. However, mechanical forces offer more opportunities beyond breaking bonds due in part to the reversibility and continuous/wide adjustability. As an complementary strategy, force may be applied to a spectator ligand to toggle the structure and reactivity of the transition metal complex incrementally and reversibly among multiple states, without incurring scissile events. In this dissertation, we study force-activity relationships of elementary steps and isolated catalytic transformations under this strategy, to build knowledge toward such multi-state mechanocatalysts. We introduce force probe ligands, a series of macrocyclic bis(phosphine) ligands containing a stiff-stilbene photoswitch, as tools to quantify force effect (Chapter 2). Each force probe ligand has a known force applied to the bis(phosphine), which is quantified by DFT methods. When employed in transition metal complexes, force probe ligands enables the measurements of force-dependent properties. In Chapter 3, we quantify the rate of C(sp2)–C(sp2) reductive elimination from platinum(II) diaryl complexes containing force probe ligands as a function of mechanical force applied to these ligands, as our first step toward force-dependent elementary step reactivity. DFT computations reveal complex dependence of mechanochemical kinetics on the structure of the force-transducing ligand. We experimentally validated 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. In Chapter 4, we move forward to mechanistic study on how forces are coupled to reactions by kinetic experiments on the stilbene isomerization (E to Z) of force probe ligand with/without platinum(II) coordination. We obtained the activation energies of free force probe ligands and (P–P)PtCl2 complexes, and results reveal the energy difference between free ligand and coordinated complex increases with restoring force, with ~ 6 kcal/mol activation energy difference change over ~ 120 pN ranges of forces on force probe ligands. We further simulated the activation energies of untethered stiff-stilbene under different tension, and found a decent consistency of computational data with empirical activation energies for free ligand. Taking the simulated energy/force relationship as a calibration curve, we estimated force experienced by stilbene in (P–P)PtCl2 complexes, which showed > 100 pN can be generated through Pt(II) coordination. The results suggest an allosteric effect by distal metal-ligand coordination can generate large forces and could drive orders-of-magnitude (up to ~104) changes in the rate of a coupled unimolecular trans/cis alkene isomerization. In Chapter 5, we quantify the rate of C(sp3)–C(sp2) reductive elimination of N,N,4-trimethylaniline from palladium(II) methyl aryl complexes employing force probe ligands, as an effort to explore other useful scopes and metal influence in force sensitivity. Analysis of the resulting first-order rate constants revealed that the rate of reductive elimination was largely invariant of ligand restoring force, as kobs varied by < 20% across the series of ligands employed. Different from the aforementioned (P–P)PtCl2 complexes, (P–P)PdArMe complexes are not stable at ambient conditions and thus generated in situ for kinetic experiments, which introduced 2 equiv. of bromide. We propose the formation of anionic complex [(P–P)PdBrArMe]- under this condition deactivates force coupling to the reductive elimination pathway. Finally, in Chapter 6, we close the catalytic cycle by demonstrations of isolated catalytic transformations of Rh(I)-catalyzed hydroformylation of 1-octene/styrene and Cu–H-catalyzed hydrosilylation of acetophenone, likewise employing force probe ligands. Over a range of ~230 pN, we found the linear to branch regioselectivity of 1-octene hydroformylation changed ~1.7 folds, and the enantioselectivity of styrene hydroformylation changed ~ 10% in ee. Cu–H-catalyzed hydrosilylation of acetophenone showed ~ 20% increase in ee as force decreases over ~ 290 pN. Low temperature NMR studies indicate the structure of (P–P)RhH(CO)2 complexes, the key intermediate that determines selectivity, remains the same across the series of ligands applied with regard to equatorial/equatorial or equatorial/apical bis(phosphine) coordination modes, while vast changes in selectivity are often resulted from changes in the coordination modes. Therefore, we propose force couples to mentioned reactions as a dynamic effect, in contrast to toggling the intermediate structure. With the limited force range accessible with this series of force probe ligand, observed changes in reaction selectivity are also limited. However, this research provides a bridge from elementary step study to polymeric matrix-supported switchable mechanocatalysis, in which wider range of forces can be achieved to provide opportunities in better force-regulated transformations.

The mechanical forces typical of daily life have the potential to induce dramatic reactivity at the molecular level. In the past few years, several studies have demonstrated that macroscopic mechanical forces can be harnessed at the molecular level, creating a new tool for the organic and materials chemist alike. These studies have created a new opportunity to develop novel, responsive materials by designing and synthesizing mechanically activated functional groups ("mechanophores") and incorporating them as stress-sensing and/or stress-responsive elements in materials.

The addition of dihalocarbenes to polybutadiene polymers forms polymeric materials that are highly susceptible to mechanochemical transformations. The mechanochemistry of the as formed gem-dihalocyclopropanated (gDHC) polymers is reported herein. The mechanochemical transformations of gDHC polymers are investigated (i) during activation in solution by the application of pulsed ultrasound, (ii) by single molecule force spectroscopy and (iii) in the solid state as a result of compressive stress.

Solution state mechanochemistry first observed during pulsed ultrasonication of gem-dichlorocyclopropanated (gDCC) polybutadiene polymers. The electrocyclic ring opening reactions of up to hundreds of gDCCs are observed on the timescale of molecular weight degradation from C-C bond scission. Mechanistic insights into the shear-induced mechanochemical transformations are obtained by monitoring the mechanochemistry as a function of gDHC halogen (dichloro-, dibromo-, bromochloro- and chlorofluoro-) and stereochemistry. The relative susceptibility of the anti-Woodward Hoffman and anti-Woodard-Hoffman-DePuy ring opening reactions through conventional pathways is explored, as is the relationship between mechanophore activity and initial polymer molecular weight.

The irreversible ring opening reaction of cis-gem-dibromocyclopropane is quantified as a function of mechanical restoring force through single molecule force spectroscopy experiments. The force-induced rearrangement proceeds at forces below covalent scission leads to a dramatic increase in the toughness of single polymer chains. Kinetic data are extracted from the force-induced rearrangment, the analysis of which reveals challenges in deconvoluting the proper reaction coordinate in force-induced reactions in polymers.

In the solid state, compressive stress is observed to induce the ring opening reactions of gDCC, gDBC and gem-bromochloro (gBCC) embedded polybutadiene polymers. Analysis of the 1H-NMR spectra following compressive activation of the materials allows the mechanoactive domains along single polymer chains to be characterized, with domain sizes on the order of only a few (3-5) monomers. The ring opening reactions of isomeric gBCCs are observed to proceed at different rates, providing the first quantitative study of selectivity in competing mechanochemical reactions in the solid state.

Transition state structures are central to the rates and outcomes of chemical reactions, but their fleeting existence often leaves their properties to be inferred rather than observed. By treating polybutadiene with a difluorocarbene source, we embedded gem-difluorocyclopropanes (gDFCs) along the polymer backbone. We report that mechanochemical activation of the polymer under tension opens the gDFCs and traps a 1,3-diradical that is formally a transition state in their stress-free electrocyclic isomerization. The trapped diradical lives long enough that we can observe its noncanonical participation in bimolecular addition reactions. Furthermore, the application of a transient tensile force induces a net isomerization of the trans-gDFC into its less-stable cis isomer, leading to the counterintuitive result that the gDFC contracts in response to a transient force of extension. Additionally, the bimolecular reaction of adjacent, tension trapped 1,3-diradicals was monitored resulting in the first example of a reaction between two formal transition state species.

Mechanochemistry has been extensively investigated as a novel method to modulate the properties of polymers. Among them, various functional groups that are sensitive to external force, which are so called mechanophores, have been synthesized that are able to change color, release stored length or release small molecules. A group of molecules, gem-dihalocyclopropanes (gDHC) have emerged as versatile mechanophores. This dissertation delves into various gDHC, encompassing their role in the network degradation and the discovery of a new mechanophore being able to release hydrogen fluoride upon the external force. Furthermore, we examined the mechanochemical reactivity with different positions of oxygen substitution on gDHC derivatives. Polymers that amplify a transient, external stimulus into changes in their morphology, physical state, or properties continue to be desirable targets for a range of applications. Therefore, in the first Chapter, we report a polymer comprising an acid-sensitive, hydrolytically unstable enol ether backbone onto which is embedded gem-dichlorocyclopropane (gDCC) mechanophores through a single post-synthetic modification. The gDCC mechanophore releases HCl in response to large forces of tension along the polymer backbone, and the acid subsequently catalyzes polymer deconstruction at the enol ether sites. Pulsed sonication of a 61 kDa PDHF with 77% gDCC on the backbone in THF with 100 mM H2O for 10 min triggers the subsequent degradation of the polymer to a final molecular weight of less than 3 kDa after 24 h standing, whereas controls lacking either the gDCC or the enol ether reach final molecular weights of 38 kDa and 27 kDa, respectively. The process of sonication, along with the presence of water and existence of gDCC on the backbone, significantly accelerates the rate of polymer chain deconstruction. Both acid generation and the resulting triggered polymer deconstruction are translated to bulk, cross-linked polymer networks. Networks formed via thiol-ene cross-linking and subjected to unconstrained quasi-static uniaxial compression dissolve on timescales that are at least three times faster than controls where the mechanophore is not covalently coupled to the network. We anticipate that this concept can be extended to other acid-sensitive polymer networks for the stress-responsive deconstruction of gels and solvent-free elastomers. After the investigation into the degradation capability of gDCC-PDHF embedded in the network, we recognize that while the proton in HCl is useful, the release of additional useful molecules or ions after the external force application could broaden the scope of the application and help us to understand the mechanism of acid release better. Therefore, hydrogen fluoride (HF) is a promising candidate. 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. In Chapter 2, the mechanochemically coupled generation of HF from alkoxy-gem-difluorocyclopropane (gDFC) mechanophores derived from difluorocarbene addition to enol ethers is reported. 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 one equivalent 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 optical response and to degrade poly(norbornene) with embedded HF-cleavable silyl ethers (20 mol%). The alkoxy-gDFC mechanophore thus provides a mechanically coupled mechanism of releasing HF for polymer remodeling pathways that complements previous thermally driven mechanisms. After learning that the alkoxy-substituted gDHCs are useful since they are capable of releasing HCl or HF, I further investigated their mechanochemical reactivity from single molecule force spectroscopy (SMFS). Subsequent findings indicate that the presence of alkoxy substitution on -carbon leads to a significant impact of lowering activation force. Additionally, the specific position of alkoxy influences the force sensitivity. To better understand the effect of alkoxy-substitution of gDHCs, we use single molecule force spectroscopy (SMFS) to study reactivities of two different alkoxy substituents on both gDCC and gDFC. The results reveal that gDHCs with alkoxy-substitution on the main chain exhibit greater force sensitivity compared to those with methoxy substituents as side chains. When methoxy group is substituted on the -carbon of cyclopropane, MeO-gDCC has over 400 pN decrease, and approximately same amount of force decrease for MeO-gDFC. The AkO-gDHCs have lower force than MeO-gDHCs, and about 200 pN lower for AkO-gDCC, and 100 pN lower for AkO-gDFC. Furthermore, the specific location of the oxygen atom also has a distinct influence on trans gDCC which has over 400 pN larger activation force than trans AkO gDCC. However, trans gDFC has approximately same activation force as trans AkO-gDFC. In conclusion, the study has developed a new system of gDHC derivatives based on PDHF, with the demonstration of being able to degrade the network and releasing HCl, and releasing self-amplified HF. The research further reveals that different oxygen substitution positions of gDHC derivatives also influence their mechanochemical reactivities. Through the study, we have acquired a more profound comprehension of gDHCs derivatives, ring-opening mechanisms and HCl and HF release mechanisms.

It is now well appreciated that coupled mechanical forces can influence the rates and outcomes of covalent chemical reactions in isolated polymers and in bulk polymeric materials. Mechanochemical reactions have been widely used in mechanocatalysis, release of small molecules and protons, biasing and probing reaction pathways, stress reporting, stress strengthening and degradable polymers. Mechanochemical reactions involve much more than simply breaking of bonds, and there exist rich opportunities for new reactions to be developed for a wide range of potential applications. In this dissertation, we report new mechanochemical reactions of three types: addition, elimination, and isomerization.Mechanical forces have been used previously to activate latent catalysts by accelerating dissociation of an inhibiting ligand, but tuning catalytic activity by force remains limited to a single demonstration of force-dependent enantioselectivity of Heck and Trost reactions. Chapter 2 describes how force affects the rate of oxidative addition, often the first step within a catalytic cycle. We study 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 are generated using a stiff stilbene force probe. We find that 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 applied forces exert an opposite effect on oxidative addition relative to that for reductive elimination, laying the groundwork for mechanically switchable catalysts that can be optimized for individual steps within a closed catalyst cycle. Chapter 3 demonstrates a new mechanochemical elimination reaction, namely the mechanical release of hydrogen fluoride, and its application to triggered polymer degradation. As a versatile reagent for material remodeling, hydrogen fluoride has 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. We achieve the mechanochemically coupled generation of HF from 2-methoxy-gem-difluorocyclopropane (MeO-gDFC) mechanophores in polymers. Pulsed ultrasonication of a MeO-gDFC containing polymer leads to one equivalent of HF release per MeO-gDFC activation. We further quantify the mechanochemical reactivity of MeO-gDFC by single molecule force spectroscopy, and force-coupled rate constants for ring opening reach ~36 s-1 at a force of ~890 pN, 400 pN lower than is required in dialkyl gDFC mechanophores that lack the methoxy substituent. The SMFS and sonication results suggest that MeO-gDFC is a more efficient mechanophore source of HF than its 2-methoxy-gem-dichlorocyclopropane analog is of HCl, in contrast to expectations based on trends in force-free reactivity. We apply the mechanical release of HF to accelerate the degradation of a copolymer containing both MeO-gDFC (3 mol%) and an HF-cleavable silyl ether (25 mol%). The mechanochemical reaction of MeO-gDFC thus provides a mechanically coupled mechanism of releasing HF for polymer remodeling pathways that complements previous thermally driven mechanisms. Finally, in Chapter 4, we report the mechanically driven isomerization of cubane, a compound of longstanding fascination to chemists due to its structure, symmetry, and strain. The mechanical coupling is explored at three regiochemical dispositions: ortho, meta and para. In contrast to the fact that all compounds can be activated thermally, cubane is mechanically activated only when coupled at ortho positions. Through mechanical activation, cubane reacts to form a thermally inaccessible syn-tricyclooctadiene product, in comparison to cyclooctatetraene, which is observed in thermal rearrangements of cubane. Pulsed ultrasonication of such cubane-containing polymer leads to efficient isomerization (57% activation after 4 h sonication). We further quantify the mechanochemical reactivity of cubane by single molecule force spectroscopy, and force-coupled rate constants for ring opening reach ~33 s-1 at a force of ~1.55 nN, lower than required forces of cyclobutanes which are typically 1.8-2.0 nN.

The coupling of mechanical stress fields in polymers to covalent chemistry (polymer mechanochemistry) has provided access to previously unattainable chemical reactions and polymer transformations. In the bulk, mechanochemical activation has been used as the basis for new classes of stress-responsive polymers that demonstrate stress/strain sensing, shear-induced intermolecular reactivity for molecular level remodeling and self-strengthening, and the release of acids and other small molecules that are potentially capable of triggering further chemical response. The potential utility of polymer mechanochemistry in functional materials is limited, however, by the fact that to date, all reported covalent activation in the bulk occurs in concert with plastic yield and deformation, so that the structure of the activated object is vastly different from its nascent form. Mechanochemically activated materials have thus been limited to “single use” demonstrations, rather than as multi-functional materials for structural and/or device applications. Here, we report that filled polydimethylsiloxane (PDMS) elastomers provide a robust elastic substrate into which mechanophores can be embedded and activated under conditions from which the sample regains its original shape and properties. Fabrication is straightforward and easily accessible, providing access for the first time to objects and devices that either release or reversibly activate chemical functionality over hundreds of loading cycles.

While the mechanically accelerated ring-opening reaction of spiropyran to merocyanine and associated color change provides a useful method by which to image the molecular scale stress/strain distribution within a polymer, the magnitude of the forces necessary for activation had yet to be quantified. Here, we report single molecule force spectroscopy studies of two spiropyran isomers. Ring opening on the timescale 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. Importantly, quantifying the magnitude of forces required to activate individual spiropyran-based force-probes enables the probe behave as a “scout” of molecular forces in materials; the observed behavior of which can be extrapolated to predict the reactivity of potential mechanophores within a given material and deformation.

We subsequently translated the design platform to existing dynamic soft technologies to fabricate the first mechanochemically responsive devices; first, by remotely inducing dielectric patterning of an elastic substrate to produce assorted fluorescent patterns in concert with topological changes; and second, by adopting a soft robotic platform to produce a color change from the strains inherent to pneumatically actuated robotic motion. Shown herein, covalent polymer mechanochemistry provides a viable mechanism to convert the same mechanical potential energy used for actuation into value-added, constructive covalent chemical responses. The color change associated with actuation suggests opportunities for not only new color changing or camouflaging strategies, but also the possibility for simultaneous activation of latent chemistry (e.g., release of small molecules, change in mechanical properties, activation of catalysts, etc.) in soft robots. In addition, mechanochromic stress mapping in a functional actuating device might provide a useful design and optimization tool, revealing spatial and temporal force evolution within the actuator in a way that might also be coupled to feedback loops that allow autonomous, self-regulation of activity.

In the future, both the specific material and the general approach should be useful in enriching the responsive functionality of soft elastomeric materials and devices. We anticipate the development of new mechanophores that, like the materials, are reversibly and repeatedly activated, expanding the capabilities of soft, active devices and further permitting dynamic control over chemical reactivity that is otherwise inaccessible, each in response to a single remote signal.

Most elastomers undergo strain-induced crystallization (SIC) under tension; as individual chains are held rigidly in a fixed position by an applied strain, their alignment along the strain field results in a shift from strain-hardening (SH) to SIC, a sub-type of SH. A similar degree of stretching is associated with covalent mechanochemical responses, raising the possibility of an interplay between the macroscopic response of SIC, and the molecular response of mechanophore activation. Here we report thiol-yne-derived stereoelastomers, doped covalently with a dipropiolate-derivatized spiropyran (SP) mechanophore. Material properties of SP-containing films are consistent with undoped controls, indicating that the SP behaves as a reporter of the mechanical state of the nascent polymer. Uniaxial tensile tests reveal correlations between mechanochromism, SH, and SIC, which are each strain rate-dependent. When mechanochromic films are stretched slowly to the point of mechanophore activation, the covalently-tethered mechanophore remains trapped in a force-activated state, even after the applied stress is removed; additionally, the kinetics of mechanophore reversion correlate highly with the extent of SIC. Because these elastomers are not cross-linked, they are recyclable by melt-pressing into new films, which increases their potential range of strain-sensing and shape-memory applications.