*#align(center)[#smallcaps[@molecularly-shielded-on-demand-ultrasound-cured-polymer-networks[Chapter]]]* = #smallcaps[Molecularly shielded, on-demand, ultrasound-cured polymer networks] Reprinted (adapted) with permission from Lorenzana, A. A. _et al._ Molecularly Shielded, On-Demand, Ultrasound-Cured Polymer Networks. #emph[Macromolecules] #strong[57], 6465--6473 (2024). Copyright 2024 American Chemical Society. == Abstract Networks formed from polymers can range from soft hydrogels to ultrahard protective coatings, making them useful for a wide range of applications from cell culture to highly bonded adhesives. Polymer networks are commonly crosslinked _via_ heat or high energy light, and recently mechanical force has also been used to induce the formation of crosslinks in pre-existing networks. Here, I demonstrate a new strategy to use mechanical deformation and ultrasound to induce liquid-to-solid crosslinking. I synthesized graft copolymers with large poly(ethylene glycol) (PEG) side-chains acting as molecular shielding groups to protect otherwise highly reactive epoxide group. Solutions of highly shielded polymers could remain as a liquid solution when left undisturbed, and I could initiate gelation of these solutions with ultrasound in 20 seconds. These ultrasound-sensitive polymers are particularly useful in light and heat sensitive applications, and where precise control over the gelation time is required. == Introduction Polymer networks can be crosslinked _via_ permanent covalent bonds. Polymer networks can include super-soft hydrogels that mimic human tissue,@rimmer2007 protective ultra-hard coatings,@villani2015 and highly bonded adhesives.@wang2018 Highly crosslinked lightweight networks, such as those formed with epoxide, are crucial in industrial applications like transportation, where reducing vehicle weight improves passenger safety and reduces harmful greenhouse gas emissions. The process of crosslinking or "curing" polymers is typically accomplished via a) mixing, b) heat, c) high energy light, or d) electron beams.@frounchi2006 Heat and light are popular routes, as they facilitate curing on-demand, allowing liquid application to a substrate. However, light and heat are not always feasible, as light cannot pass through opaque materials, and heat can damage delicate or flammable substrates. Electron beams are also popular industrially due to their high energy efficiency and excellent uniformity, however transmittance through metals can be challenging. Alternatively, natural polymers (e.g. peptides, saccharides, nucleic acids), can form networks in response to temperature, light, and solvents by partially unfolding, thus exposing previously buried, or "cryptic", binding sites. Of particular interest to us, these cryptic binding sites can also be revealed in response to a mechanical stimulus.@brown2009@bu2012 For example, fibronectin will dynamically unfold and polymerize into fibrils in response to cell-generated forces.@gee2008@smith2007@oberhauser2002 In contrast, synthetic polymers commonly weaken or even rupture under force.@kuijpers2004 Inspired by the unfolding triggered crosslinking of proteins like fibronectin, I sought to develop a new method of installing mechanosensitivity within synthetic polymer networks. Recently, we developed organogels@tran2017 and hydrogels@sonu2023 with mechano-responsive properties, both based on preformed diacrylate crosslinks with reactive pendent thiols for post-polymerization crosslinking. Both systems begin as a crosslinked network and respond to compression, strengthening several hundreds of kPa in elastic modulus over repeated cycles. The mechanosensitivity results from long PEG molecular shielding groups grafted to the polymer backbone, which prevent the reactive thiol groups from crosslinking until compression brings them together. To date, the most successful method of creating synthetic mechanosensitive polymers that undergo liquid-to-solid transition is by inserting weak bonds, "mechanophores," within polymer chains that are converted to an active intermediate in response to force, capable of strengthening the material.@ramirez2013@lenhardt2015@hickenboth2007 Still other approaches to designing force-sensitive materials involve the design of small molecules with several ways of participating in intermolecular interactions such as hydrogen bonding, π--π stacking, and van der Waals forces. Peptide-based isomers functionalized with cholesterol and napthalic groups have been shown to create micellar assemblies that undergo a gel-gel transition with the application of ultrasound.@yu2010 This work, in contrast, uses the shielding group concept, starting with uncrosslinked, shielded polymers that can undergo a rapid liquid-to-solid transition upon application of force. To accomplish this, graft polymers bearing reactive epoxide@vidil2016 groups are mixed with small molecule amine/thiol crosslinkers. Ultrasonic irradiation is used to apply high strain rates to the shielded polymers. Straining of the graft polymers overcomes their steric barrier to interaction with the small molecule crosslinkers, facilitating a reaction, that rapidly strengthens the material. The resultant materials achieve elastic modulus values comparable to ultra hard commercial epoxy coatings. I anticipate that these shielded polymers will be useful as extremely hard and solvent-resistant coatings and as adhesives that can be cured by focusing ultrasound through the surfaces the adhesive is bound to. == Materials and methods === Chemical and polymer sourcing Materials were purchased from Sigma-Aldrich unless otherwise mentioned. (500 g/mol and 950 g/mol, PEGMA500 and respectively), glycidyl methacrylate (97%, GMA), and 2-methoxyethyl methacrylate (99%, MEMA) were passed through a column of neutral alumina to remove inhibitors before use. 2,2′-(Ethylenedioxy)diethanethiol (95%, EDT), ethylene diamine (99%, EDA), (99%, PPB), (98%, CPA), and 2-(azo(1-cyano-1-methylethyl))-2-methylpropane nitrile (98%, AIBN), 1-butanol (99.9%, BuOH), 1,4-dioxane (99%, dioxane), N,N-dimethylformamide (99.8%, DMF) were used as received. Diethyl ether (99%, ether), lithium hydroxide monohydrate (98.5%, LiOH), and acetonitrile (99%, MeCN) were purchased from Fisher Chemical and used as received. Basic alumina 60-325 mesh was purchased from Fisher Scientific and used as received. === Representative polymer synthesis Poly(GMA_-co-_PEGMA) and poly(GMA_-co-_MEMA) of all molar ratios and degree of polymerization (DP) were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. The targeted monomer ratios and DP are described in @shieldedpolymerstab. Each reaction was fed 0.01 moles of monomer total. For example, 0.71 g (0.005 mol) GMA, 0.72 g (0.005 mol) MEMA, 0.0559 g CPA (0.2 mmol), 6.6 mg AIBN (0.04 mmol) (\[50\]:\[1\]:\[0.2\] \[M\]:\[CTA\]:\[I\], where \[M\]:\[CTA\] defines the DP), 4 mL of 1,4-dioxane, and a stir bar were added to a 20 mL scintillation vial. The vial was sealed with a rubber septum and the solution was purged with N2 (g) for $tilde.op$20-30 min in an ice bath to prevent solvent and monomer evaporation (PEGMA solutions were bubbled in cool water to prevent PEG crystallization). Subsequently, the vial was placed in a thermostated aluminum reaction block at 60 °C on top of a magnetic stir/hot plate. The reaction was left to stir overnight, yielding a viscous liquid. The solution was removed from heat and exposed to air to terminate the polymerization. The solution was precipitated into cold (-20 °C) ether, the solid washed twice more with cold ether, and dried at 0.01 mbar overnight. === Polymer characterization Polymer DP and the comonomer incorporation ratio were determined through #super[1]H NMR on a Bruker Avance 500 at 500 MHz in CDCl#sub[3] (@fig:MEMAGMANMR - @fig:GMAMEMA7030).@izunobi2011 The ratio of monomers was determined by integration of #super[1]H spectral resonances of the PEGMA/MEMA methoxy protons and the methanetriyl proton of the GMA glycidyl ring, normalized to the aromatic proton peak at the para position of the CPA phenyl ring, assuming there is one Z group@keddie2012 on every polymer chain. #figure(image("Images/C2S3.png", width: 100.0%), placement: bottom, caption: [ #super[1]H NMR spectra of poly(GMA_-co-_MEMA) targeting 50 DP and 1:1 comonomer ratio. Spectra recorded at 500 MHz in CDCl#sub[3]. ] ) #figure(image("Images/C2S4.png", width: 100.0%), placement: bottom, caption: [ #super[1]H NMR spectra of poly(GMA_-co-_PEGMA500) targeting 50 DP and 1:1 comonomer ratio. Spectra recorded at 500 MHz in CDCl#sub[3]. ] ) #figure(image("Images/C2S5.png", width: 100.0%), placement: bottom, caption: [ #super[1]H NMR spectra of poly(GMA_-co-_PEGMA950) targeting 50 DP and 1:1 comonomer ratio. Spectra recorded at 500 MHz in CDCl#sub[3]. ] ) #figure(image("Images/C2S6.png", width: 100.0%), placement: bottom, caption: [ #super[1]H NMR spectra of poly(GMA_-co-_PEGMA950) targeting 50 DP and 60:40 comonomer ratio. Spectra recorded at 500 MHz in CDCl#sub[3]. ] ) #figure(image("Images/C2S7.png", width: 100.0%), placement: bottom, caption: [ #super[1]H NMR spectra of poly(GMA_-co-_PEGMA950) targeting 50 DP and 70:30 comonomer ratio. Spectra recorded at 500 MHz in CDCl#sub[3]. ] ) #figure(image("Images/C2S8.png", width: 100.0%), placement: bottom, caption: [ #super[1]H NMR spectra of poly(GMA_-co-_PEGMA500) targeting 50 DP and 60:40 comonomer ratio. Spectra recorded at 500 MHz in CDCl#sub[3]. ] ) #figure(image("Images/C2S9.png", width: 100.0%), placement: bottom, caption: [ #super[1]H NMR spectra of poly(GMA_-co-_PEGMA500) targeting 50 DP and 70:30 comonomer ratio. Spectra recorded at 500 MHz in CDCl#sub[3]. ] ) #figure(image("Images/C2S10.png", width: 100.0%), placement: bottom, caption: [ #super[1]H NMR spectra of poly(GMA_-co-_PEGMA500) targeting 50 DP and 30:70 comonomer ratio. Spectra recorded at 500 MHz in CDCl#sub[3]. ] ) #figure(image("Images/C2S11.png", width: 100.0%), placement: bottom, caption: [ #super[1]H NMR spectra of poly(GMA_-co-_MEMA) targeting 50 DP and 60:40 comonomer ratio. Spectra recorded at 500 MHz in CDCl#sub[3]. ] ) #figure(image("Images/C2S12.png", width: 100.0%), placement: bottom, caption: [ #super[1]H NMR spectra of poly(GMA_-co-_MEMA) targeting 50 DP and 70:30 comonomer ratio. Spectra recorded at 500 MHz in CDCl#sub[3]. ] ) === Copolymer solution preparation Polymer solutions were initially prepared to be 50 wt% polymer. For example, 0.3 g of polymer was dissolved in 0.3 g of solvent, and crosslinker was added such that the nucleophilic functional group was equimolar with the total epoxide concentration. To control for the concentration of crosslinking points in solution, polymers were subsequently formulated to be 1 M of epoxide in solution. For copolymers containing PEGMA2000, solutions were formulated in MeCN at 0.5 M of epoxide functional units due to the large pendant chains dominating the overall mass of the sample and crosslinked with EDT catalyzed by LiOH. Each sample was vortexed for 5 sec to ensure complete mixing before proceeding with rheometry or sonication. For all experiments crosslinked with amines, reactions were conducted in a solvent system of 1:1 BuOH:DMF. Alcohols are known to catalyze the reaction between amines and epoxides through the formation of a trimolecular complex.@ehlers2007 Thiol-crosslinked reactions were conducted in MeCN with 10 µL of 2 M LiOH as a catalyst, necessary to deprotonate the thiols in order to perform a nucleophilic attack on the epoxide ring.@gadwal2015 === Parallel plate rheology Gelation times and storage moduli ($G'$), and $t a n delta$ of polymer solutions/gels were determined on a Kinexus Pro parallel plate rheometer (Netzsch, Selb, Bayern, Germany). Measurements were run on a 20 mm plate with a 1 mm gap at 1% strain and 1 -- 100 rad s#super[-1] frequency sweep. Each frequency sweep lasted approximately 5 min, and the entire measurement lasted approximately 15 hr. The gel point was defined using the Winter-Chambon criterion, for which the time of gelation is defined as the point at which $t a n delta$ becomes frequency independent at small frequencies.@winter1986@chambon1985@chambon1987 For samples with very high modulus, the elastic modulus was determined using compressive rheology by taking the slope of the stress strain curve of cured gels with a 4 mm diameter. Rheological experiments were analyzed using IRIS Rheo-Hub (IRIS Development, Amherst, MA).@poh2022 === Sonication-induced gelation of shielded polymers Polymer solutions were sonicated using a QSonica Q500 with a microtip attachment. The microtip QSonica probe was immersed in a polymer solution in MeCN. Water was flowed across the outer surface of the tube using a custom-made jacketed beaker to control bulk temperature (University of Massachusetts Amherst Scientific Glassblowing Laboratory, Amherst, MA). Temperature was monitored with an IRT205 IR thermometer (General Tools, Secaucus, NJ) and confirmed with a mercury thermometer. This cooling setup was not sufficient to control temperature after 2 min and 40 s of sonication. Samples were sonicated at 10% amplitude and 20 kHz for 5 sec at a time, with 10 sec breaks in between pulses to avoid probe overheating. Gelation was determined by the point at which the power output would drop to $tilde.op$0 W and noise from vibrations would cease when the polymer had formed a solid gel. Samples were then immediately moved to the adjacent needle induced cavitation (NIC) setup to determine the elastic modulus immediately post sonication. === Differential scanning calorimetry Differential scanning calorimetry (DSC, Q200, TA Instruments) was used for crystallization characterization. A sample of (3-5 mg) was sealed in a standard aluminum hermetic pan using TZERO press (TA Instruments) before being added to the calorimeter with an identical empty reference pan. The equipment was lowered to -90 °C and heated to 100 °C at a rate of 5 °C/min to remove the thermal history of the sample. The equipment was then lowered to -90 °C again and heated to 100 °C at the same rate, where enthalpy of melting (\$\\Delta H\\textsubscript{m}\$) was obtained from the area of the melting curve divided by the sample weight.@kong2002 Thermogravimetric analysis (TGA, Q50, TA Instruments) was used to determine the degradation of the samples before running DSC to meet the criteria of a maximum 1.5 wt% loss. === Needle induced cavitation Characterization of elastic modulus of sonicated gels was done with needle induced cavitation (NIC) using a custom-made setup with water as the fluid, pressurized with a NE 1000 syringe pump (New Era, Farmingdale, NY), contained in a 6 mL disposable syringe with a 27-gauge stainless steel disposable needle, microstand, and Px409-015 GUSBH pressure gauge (Omega, Norwalk, CT). Data collected from NIC was recorded on a Surface Mini using a custom LabView program to interface with the pressure sensor and record the pressure values (Crosby Lab, University of Massachusetts Amherst, Amherst, MA). When calculating the elastic modulus of gels, the effects of surface tension were ignored and values were computed using Equation 1.@dougan2022@barney2020 Each NIC experiment lasted on average from 30-90 sec. $ E = frac(6 P_c, 5) $ == Results and discussion === Gelation kinetics of polymers under static conditions My goal was to create a polymer network that was shelf-stable and would gel in response to force. First, I created a suite of polymers with varying crosslinker to comonomer ratios. Shielded and control copolymers were synthesized using RAFT polymerization of PEGMA (molecular shielder, grafting-through process@li2021) or MEMA (control) with GMA monomers. Poly(GMA-co­-PEGMA) and poly(GMA_-co-_MEMA) were synthesized with varying monomer ratios (30:70 GMA:PEGMA/MEMA to 70:30 GMA:PEGMA/MEMA) and shield lengths (1, $tilde.op$10, and $tilde.op$20 PEG repeats for MEMA, PEGMA500, and PEGMA950, respectively) to determine their effect on gelation. Additionally, DP for each composition was varied to determine the effect of polymer length on force sensitivity. When developing these materials, I imagined a polymer system that would be easily spreadable onto a substrate as a liquid that would then transition to a solid state after the introduction of mechanical stimuli. The final solid material should be bonded together permanently with covalent crosslinks. To achieve this goal, I selected the monomer GMA for its robust epoxide reactive group. Epoxides are known to undergo a ring-opening reaction in the presence of nucleophiles like amines and thiols. To introduce mechano-sensitivity, I sought to copolymerize my epoxide functional monomers with monomers functionalized with groups that could provide steric hindrance. Towards this goal, GMA was co-polymerized with PEGMA of varied molecular weights from 140 to 950 g/mol that I hypothesized could provide a steric hindrance to crosslinking _via_ their ether side-chains. Synthesis of this suite of polymers proceeded as expected, with final DPs and incorporation ratios closely matching the targeted DP and feed ratio when conducted in dioxane (@shieldedpolymerstab). Successful incorporation and molar ratio of constituent monomers was confirmed using #super[1]H NMR spectroscopy (@fig:MEMAGMANMR - @fig:GMAMEMA7030). DP and incorporation ratios of poly(GMA_-co-_PEGMA) samples were less consistent compared to their MEMA counterparts, attributed to the inherent dispersity of PEGMA macromonomers skewing the actual molar amount added to reactions. After successfully synthesizing the desired copolymers, I moved on to assess their gelation kinetics. #figure( placement: auto, align(center)[#table( columns: 5, align: (center,right,right,right,right,right,right,), table.header([Name], [Target DP], [Feed ratio], [Actual DP], [Actual ratio],), table.hline(), [50:50 GMA:MEMA], [50], [1:1], [73], [55:45], [50:50 GMA:PEGMA500], [50], [1:1], [122], [51:49], [50:50 GMA:PEGMA950], [50], [1:1], [91], [56:44], [60:40 GMA:PEGMA950], [50], [60:40], [102], [62:38], [70:30 GMA:PEGMA950], [50], [70:30], [87], [72:28], [30:70 GMA:PEGMA500], [50], [30:70], [76], [30:70], [60:40 GMA:PEGMA950], [50], [60:40], [119], [60:40], [70:30 GMA:PEGMA500], [50], [70:30], [95], [68:32], [60:40 GMA:MEMA], [50], [60:40], [134], [60:40], [70:30 GMA:MEMA], [50], [70:30], [140], [70:30], [50:50 GMA:PEGMA950 25DP], [25], [1:1], [34], [1:1], [50:50 GMA:PEGMA950 50DP], [50], [1:1], [61], [54:46], [50:50 GMA:PEGMA950 100DP], [100], [1:1], [93], [1:1], [50:50 GMA:PEGMA950 150DP], [150], [1:1], [130], [52:48], [50:50 GMA:PEGMA950 200DP], [200], [1:1], [191], [57:43], )] , caption: [Polymers used in each experiment, their target DP, comonomer feed ratio, actual DP, and actual comonomer ratio as determined by #super[1]H NMR.] , kind: table ) For the crosslinkers, I chose EDT due to its non-volatile nature and reasonable stability in air, and EDA as it is commonly used to cure epoxy resins. Amines and thiols were chosen as two candidates both because they are frequently used in commercial epoxy formulations and to compare the effects of different reaction kinetics on the shielded copolymer system. I sought to determine a molecular weight of shielding groups that would facilitate delayed crosslinking of the epoxide groups in the presence of a bifunctional nucleophile without preventing it entirely. In my experiments, I tested a range of effects including varying the DP of grafted chains from 1 to 20, varying the DP of the polymer backbone from 25 to 670, adjusting nucleophilic attack kinetics, and varying the ratio of comonomers from 30 to 70% GMA concentration. The monomers used to form the copolymers and the different crosslinkers in these experiments are represented in @fig:shieldinglength a. #figure(image("Images/C2F1.png", width: 100.0%), placement: auto, caption: [ Large molecular shields inhibit or delay crosslinking. (a) Illustrations of polymer components used throughout the paper. (b) Effect of shielding group functionality on storage modulus ($G'$) over time with amine crosslinks at constant 50 wt % polymer, reacting with EDA. Inset depicts high density poly(GMA_-co-_MEMA) with many epoxy groups. (c) Effect of shielding group functionality on storage modulus over time with amine crosslinks at constant 1 M concentration epoxy, reacting with EDA. Inset depicts low density poly(GMA_-co-_MEMA) with a fixed amount of epoxy groups. (d) Effect of shielding group functionality on storage modulus over time with thiol crosslinks at constant 1 M concentration epoxy, reacting with EDT. Inset depicts poly(GMA_-co-_PEGMA950) with a fixed amount of epoxy groups and large shielding groups preventing crosslinking. For all experiments, a 1:1 ratio of GMA:MEMA, PEGMA500, or PEGMA950 was used. Error bars show the standard deviation of $G'$ at each timepoint (n = 3). For all conditions, including the enhanced kinetics provided by the thiol-epoxy reaction, a latency period before gelation at static conditions is present. ] ) First, the effect of pendent shield size on crosslinking was assessed at constant weight percent and static conditions (@fig:shieldinglength b). When solutions are formulated at 50 wt% of polymer with EDA, poly(GMA_-co-_MEMA) crosslinks very quickly (1 h) and reaches a final $G'$ on the order of 106 Pa. Conversely, poly(GMA_-co-_PEGMA500) crosslinks more slowly (8 h) and reaches a final $G'$ on the order of 104 Pa, and poly(GMA_-co-_PEGMA950) shows no change in modulus indicating no crosslinking occurred. At constant 50 wt% of polymer in solution, the concentration of epoxide for unshielded samples (MEMA) is very high compared to the shielded polymers (PEGMA). At this fixed concentration, the overall mass for the shielded polymer solutions is dominated by the presence of ether in the PEGMA side chains, skewing the sample in favor of unreactive ether and decreasing the number of possible crosslinks. The lack of increase in modulus with PEGMA950 may be due to this ether dominance preventing the formation of a volume-spanning network. Additionally, the relatively large mass of the ether side-chains decreases the amount of reactive epoxy in solution. To control for the effect of variable epoxide concentration, samples were next formulated at a constant epoxide molar concentration (@fig:shieldinglength c). Epoxide concentration was set to 1 M, resulting in variable weight percent polymer in solution: control polymer samples with low (25%) and shielded samples with high (61%) weight percent. At 25 wt%, poly(GMA_-co-_MEMA) crosslinks more slowly (2 h) than at 50 wt% and reaches a lower final $G'$ on the order of 105 Pa. For poly(GMA_-co-_PEGMA950), wt% changes from 50 to 61 and expectedly shows only a small increase in $G'$ of 35 Pa. For poly(GMA_-co-_PEGMA500 samples, 1 M epoxide concentration is equal to 50 wt% of polymer. Trends in the effect of shielding groups are the same at constant wt% polymer or mol% epoxides: as the shielding group MW increases, the time to gelation and the final modulus both decrease. Finally, the effect of more reactive nucleophiles on crosslinking were investigated by replacing EDA with EDT and keeping the mol% epoxide constant (@fig:shieldinglength d). Thiols are known to be stronger nucleophiles than primary amines, and the ring opening reaction between thiols and epoxides proceeds orders of magnitude faster than between amines and epoxides.@t.nguyen2013 At a constant 1 M epoxide concentration, poly(GMA_-co-_MEMA) with EDT crosslinked more rapidly (30 min) than the amine condition and attained a similar final $G'$. Poly(GMA_-co-_PEGMA500) samples crosslinked rapidly (42 min) with EDT, but more slowly than the MEMA copolymer and attained a final modulus on the order of 104 Pa. Poly(GMA_-co-_PEGMA950) samples still did not show any signs of gelation, increasing only to a final modulus of 10 Pa. Even with faster reaction kinetics, the PEGMA950 shielding groups suppress gelation. For permanently crosslinked polymer networks, the equilibrium modulus of the cured material can be predicted by Flory's theory of rubber elasticity@flory1941@flory1953 and is proportional to the number of elastically effective chains in the network.@ferry1980@kulicke1989 As the number of elastically effective chains increases, so does the equilibrium modulus; therefore, a low equilibrium modulus implies the presence of unreacted crosslinks. With the same number of crosslinks possible in MEMA, PEGMA500, and PEGMA950 samples, and taking the equilibrium modulus of the MEMA polymer in @fig:shieldinglength c, PEGMA500 and PEGMA950 can be inferred to be have a lower crosslinking desntiy due to the protective effects of the polyether chains. This led us to believe that 950 g/mol shielding groups are most effective at creating a steric barrier to reaction, preventing crosslinking between adjacent polymers and resulting in lower final $G'$ values. === Controlling gel time through shield graft density We next aimed to determine the minimum molar ratio of shielding groups necessary to prevent spontaneous crosslinking by varying the ratio of GMA:PEGMA (@fig:shieldingratio a). I expected that high contents of shielding monomer would entirely inhibit gelation over the measurement time, eventually prohibiting crosslinking even under force. To assess the minimum molar ratio necessary for preventing gelation without applied mechanical stimulus, the mole percent of PEGMA950 ($tilde.op$20 repeat units) and PEGMA500 ($tilde.op$10 repeat units) shielding monomers within each polymer chain was varied from 30 to 50 mol%. Variations in mole percent of MEMA copolymers was assessed as a negative control. The total concentration of epoxides in solution remained constant at 1 M. #figure(image("Images/C2F2.png", width: 100.0%), placement: auto, caption: [ Ratio of pendent shields to reactive groups controls gelation time. (a) Illustrations of polymers at different GMA:PEGMA molar ratios, showing the change in backbone flexibility and exposed reactive sites. b-e. Storage modulus evolution over time for: (b-c) varying mole percentage of PEGMA950 with a diamine (b) or dithiol (c) crosslinker; (d) varying mole percentage of PEGMA500 and (e) MEMA with a diamine crosslinker. Arrows represent trends in shielding resulting from increased ratio of shielding monomer. ] ) In the presence of EDA or EDT with shielding group concentrations at mol 50% (PEGMA950), a negligible increase in $G'$ was seen; at 40%, a very slow increase in $G'$ with a final value on the order of 103 Pa was demonstrated; and at 30%, a rapid increase in $G'$ with a final $G'$ of 104 Pa (@fig:shieldingratio b-c). At higher shielding monomer percentages, gelation was entirely inhibited over the measurement time, even with the quick crosslinking EDT. In both the thiol and amine cases, the trend toward decreasing gel time with increasing PEGMA950 content is the same. Next, polymers with PEGMA500 shielding units ($tilde.op$10 repeat units) were varied from 30 to 70 mol% shielding monomer content while keeping the total epoxide group concentration in solution constant at 1 M (@fig:shieldingratio d) with EDA. When the shielding group concentration was 30 and 40 mol%, the material crosslinks rapidly and reaches final $G'$ values on the order of 105 Pa. At 50% concentration of shielding groups, the material reaches a lower final modulus on the order of 104 Pa. At the maximum tested 70% molar ratio of shielding group to reactive group, the shielded polymers still form a gel, but do not attain an equilibrium modulus during the experimental timeframe. The PEGMA500 shielding groups do not provide a sufficient steric barrier to reaction but do provide some hinderance to reaction evidenced by the decreased final modulus values compared to control samples. Finally, polymers with one repeat unit pendent chains (MEMA) were varied between 30 and 50 mol% control monomer and reacted in the presence of EDA. Increasing the control monomer ratio from 30 to 50% slightly decreased to rate at which the material crosslinked and the final modulus, from 105 Pa at 30 and 40 mol% control monomer to just above 104 Pa at 50 mol% control monomer (@fig:shieldingratio e). As expected, the small size of the MEMA comonomer did not contribute significantly to suppressing the crosslinking kinetics of the crosslinking polymers. At low ratios of shielding monomer to reactive monomer, there are statistically likely to be more stretches of reactive monomer with no steric effects to prevent them from crosslinking, as well as increased backbone flexibility. At high ratios of shielding monomer to reactive monomer, there are far fewer reactive monomer sequences as well as a straighter backbone due to pendent chains preventing backbone flexing. In summary, only the compositions achieved this with a high degree of shielding. Gelation was completely inhibited at a 1:1 ratio of reactive to shielding groups. This composition was selected as the most promising candidate for force-activated gelation. === Force-induced gelation of shielded polymers We hypothesized sonication would be a facile method to mechanically induce gelation of shielded polymer. Sonication can achieve enormous strain rates approaching 10#super[8] s#super[-1].@hennrich2007 This enormous strain rate arises from cavitations introduced during ultrasonic irradiation, nearly instantaneously creating and destroying microscopic bubbles that in turn create pressure gradients able to apply force through fast solvent flows to polymers of sufficient size. The force accumulated along the polymer backbone result in overstretched regions, which is what is generally accepted to drive conventional mechanochemical reactions.@oneill2023 #figure(image("Images/C2F3.png", width: 100.0%), placement: auto, caption: [ Sonication induces shielded polymer crosslinking. (a) Gel time of poly(GMA_-co-_PEGMA950) under static and sonicated conditions at varying DP with 1:1 molar ratio. Samples at 25 and 50 DP did not form a gel. Insets show a liquid polymer solution during a bubble test and a polymer cured through sonication, still attached to the sonicator probe. (b) Elastic modulus of poly(GMA_-co-_PEGMA950) cured with sonication as measured _via_ NIC. Samples were crosslinked with a 1:1 molar ratio of thiol to epoxy and at a DP of 100, 150, or 200 and measured 60 s post sonication and after two weeks. ] ) Crosslinking of shielded polymers induced #emph[via] sonication was assessed at DP of 25 to 200 monomer units per chain (@fig:sonication a). Each polymer sample was prepared at 1 M epoxide group concentration and reacted with EDT catalyzed by LiOH. Utilizing an ultrasonic probe immersed in polymer solutions, samples were subjected to ultrasonic waves for 5 s at a time, with 10 s of pause in between to prevent probe overheating. All conditions have delayed gelation at static conditions, allowing for the characterization of faster crosslinking with induced strain. At DP equal or greater to 100, samples gelled within 60 s of sonication time. At 100 DP, I observed a two order of magnitude decrease in gelation time when comparing unperturbed samples with sonicated samples. Samples of DP 150 and 200 gelled more rapidly, within 30 and 20 seconds of sonication time, respectively. Poly(GMA_-co-_PEGMA950) of lower DP (25 and 50) did not show any strain responsiveness, and the solution boiled before any gelation or viscosity change was observed due to the heat generated by the ultrasonic probe, reaching a temperature of 56 °C measured through an IR thermometer, at which point the solution began to boil while sonication was being applied. Counterintuitively, the heat generated by sonication is counterproductive to gelation of this system, possibly due to changes in the conformation of PEGMA shielding groups at higher temperatures (@fig:shieldedtemp). It is well understood that PEGMA copolymers have a lower critical solution temperature in water that is dependent on the polyether length and the ionic strength of the environment,@lutz2006 but it is not clear that this behavior extends into aprotic organic solvents. Gelation time under static conditions decreased as a function of DP like sonicated samples but showed a leveling off after 150 DP unlike the sonicated samples. This decrease in gel time is likely due to the longer backbone lengths of the polymers beginning closer to the percolation threshold for gelation, resulting in fewer epoxide-thiol reactions needing to take place to form a volume spanning elastic path and a shorter time to the critical gel.@daoud2000@winter2016 #figure(image("Images/C2S1.png", width: 100.0%), placement: auto, caption: [ Evolution of $G'$ for poly(GMA_-co-_PEGMA950) at a 1:1 molar ratio of comonomers and 25 DP during parallel plate rheology. Frequency sweeps were run from 1 to 100 rad/s over 17.5 hrs using a 20 mm top plate. Data plotted at 1 Hz and 1% strain. At 25 °C the sample increases in modulus rapidly after a 2.5 hr latency period. At 40 °C the same shows a small uptick in modulus after 12.5 hrs and never fully gels during the measurement period. ] ) It has been shown that polymers of sufficient molecular weight are sensitive to shear forces. The large size of polymers results in restriction of bond angle conformers available due to chain and bond torsional strain, meaning polymers can accumulate force along their backbone as entropic potential energy.@wang2013@hermes2011@shi2006@cui2009 High molecular weight polymers undergo chain scission in response to strong shear forces generating two distinct carbon-centered radicals.@caruso2009@beyer2005 These sufficiently strong shear forces result in overstreched segments of polymer adjacent to the chain center, generating a tensile force that drives mechanochemical reactions.@oneill2023 The chain scission rate increases with molecular weight.@madras2000 This molecular weight dependence is more accurately described as a polymer length dependence.@may2016 It follows that shielded poly(GMA_-co-_PEGMA950) of sufficient DP is more easily influenced by shear forces in solution if the chain length is long enough, surpassing at least 100 units in length. The increased DP of the polymer also increases the viscosity of the sample. Prior literature has shown that highly viscous media decreases the effectiveness of ultrasonic micromixing,@monnier1999 making it less likely that the dependence of gel time on DP is a result of mixing phenomena. This study does not elucidate the mechanism for this system's strain sensitivity. It is not clear what aspect of crosslinking is sped up by the application of ultrasound, the addition of EDT to polymer or the addition of polymer+EDT to another polymer. Future studies using mono-thiols functionalized with UV tags would shed light on the precise molecular mechanism of strain-sensitive crosslinking. Cavitation rheology was used to assess post-gelation elastic moduli of gels formed _via_ sonication (@fig:sonication b). NIC has previously been shown to be effective at extracting elastic modulus information from soft materials.@dougan2022 Sonicated samples were measured to have an elastic modulus near 1 kPa for samples starting at 100 DP, and 20 kPa for samples between 150 and 200 DP as measured by NIC. After a week of resting in a sealed tube to allow for residual epoxides to be consumed by thiols, the modulus of each sample increased to an average of 20 kPa for samples starting at 100 DP and 60 kPa for samples starting at 150 to 200 DP. The final modulus for 150 and 200 DP polymers had a wide range, varying from 30 to 170 kPa. This variance is likely error from cavitation rheology, which tends to have higher variance for samples with higher elastic moduli.@zimberlin2007@barney2019 The modulus derived from NIC shows polymers shielded with PEGMA950 cure into relatively weak materials. === Ultrahard materials from shielded copolymers Conventional epoxy resins and composites can attain $G'$ values approaching and surpassing 10#super[9] Pa.@baral2008@maka2015 Choosing this value as a benchmark for comparison, I formulated poly(GMA_-co-_PEGMA2000) copolymers at a 1:1 monomer ratio and 670 DP. The extremely long shielding group and long DP were chosen to provide a material that had both maximum latency and sensitivity to ultrasound. After sonicating these samples and leaving them to cure for 48 hr, the polymer crosslinked into an opaque white solid. Samples were prepared as 5x4 mm cylinders, and their moduli were assessed on a rheometer via compression with a 4 mm diameter plate. An elastic modulus value of 62 MPa was extracted from the resultant stress-strain curve (@fig:ultrahardshield a), approaching that of conventional epoxy materials. Immersing gels of this copolymer into acetone and ethanol showed no visible change in the material, but in MeCN, DCM, and water the gels crumbled into insoluble chunks (@fig:ultrahardshield b), leading me to conclude that the material's strength comes from a combination of epoxide-thiol covalent crosslinks and PEG side chain crystallization. It is well known that graft copolymers with crystallizable side chains will form crystal domains.@takeshita2010@inomata2005 Using DSC I was able to measure a melting temperature for a cured GMA:PEGMA2000 sample. confirming the material is partially crystallized (@fig:dsc). Using a steric shielding approach, I created an ultrahard material through an unexpected combination of crystallinity and covalent bonding. #figure(image("Images/C2F4.png", width: 100.0%), placement: auto, caption: [ Shielded copolymers create ultrahard and durable materials. (a) Compression modulus of a fully cured poly(GMA_-co-_PEGMA2000) with 1:1 molar ratio of monomers. Elastic modulus is calculated by taking the slope during the linear portion of the stress-strain curve. Red line shows the linear best fit through four points. (b) Fully cured poly(GMA_-co-_PEGMA2000) gels immersed into acetone, ethanol, water, acetonitrile, and dichloromethane. ] ) #figure(image("Images/C2S2.png", width: 100.0%), placement: auto, caption: [ Differential scanning calorimetry thermogram of 1:1 GMA:PEGMA2000 crosslinked with EDT with all acetonitrile solvent evaporated off. $Δ$H#sub[m] of the sample was calculated to be 97.9 J/g with T#sub[m] at 49.29 °C. ] ) == Conclusion We synthesized novel strain-sensitive shielded polymers containing both reactive epoxides and molecular shields. These shielding PEG chains provide a steric barrier to an otherwise powerful and efficient crosslinking reaction between amines or thiols and epoxides. This approach to creating strain sensitive materials provides a facile route to creating strain responsive coatings and adhesives, using well-known and commercially available monomers. Through this I demonstrated, for the first time, a liquid-to-solid transition accelerated under force using shielded reactive polymers. I showed that force stimulated gelation could be achieved with ultrasound. I further showed that steric shielding can create ultrahard materials. Suppressed gelation without force, combined with ultrasound sensitivity, make this polymer an ideal candidate for an adhesive in a heat or light sensitive application. #emph[The work in this chapter represents a collaboration with Jichao Song and Professor Jessica Schiffman from the Chemical Engineering Department at University of Massachusetts Amherst. DSC measurements in @fig:dsc were conducted and data analyzed by Jichao Song. NIC data was collected and analyzed by Hsu Shwe Yee Naing.]