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PhD-Dissertation Chapter2.typ
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== Abstract<abstract>Networks formed from polymers can range from soft hydrogels to ultrahardprotective coatings, making them useful for a wide range of applicationsfrom cell culture to highly bonded adhesives. Polymer networks arecommonly crosslinked _via_ heat or high energy light, and recentlymechanical force has also been used to induce the formation ofcrosslinks in pre-existing networks. Here, I demonstrate a new strategyto use mechanical deformation and ultrasound to induce liquid-to-solidcrosslinking. I synthesized graft copolymers with large poly(ethyleneglycol) (PEG) side-chains acting as molecular shielding groups toprotect otherwise highly reactive epoxide group. Solutions of highlyshielded polymers could remain as a liquid solution when leftundisturbed, and I could initiate gelation of these solutions withultrasound in 20 seconds. These ultrasound-sensitive polymers areparticularly useful in light and heat sensitive applications, and whereprecise control over the gelation time is required.
== Introduction<introduction>Polymer networks can be crosslinked _via_ permanent covalent bonds.Polymer networks can include super-soft hydrogels that mimic humantissue,@rimmer2007 protective ultra-hard coatings,@villani2015 andhighly bonded adhesives.@wang2018 Highly crosslinked lightweightnetworks, such as those formed with epoxide, are crucial in industrialapplications like transportation, where reducing vehicle weight improvespassenger safety and reduces harmful greenhouse gas emissions. Theprocess of crosslinking or "curing" polymers is typically accomplishedvia a) mixing, b) heat, c) high energy light, or d) electronbeams.@frounchi2006 Heat and light are popular routes, as theyfacilitate curing on-demand, allowing liquid application to a substrate.However, light and heat are not always feasible, as light cannot passthrough opaque materials, and heat can damage delicate or flammablesubstrates. Electron beams are also popular industrially due to theirhigh energy efficiency and excellent uniformity, however transmittancethrough metals can be challenging.
Alternatively, natural polymers (e.g. peptides, saccharides, nucleicacids), can form networks in response to temperature, light, andsolvents by partially unfolding, thus exposing previously buried, or"cryptic", binding sites. Of particular interest to us, these crypticbinding sites can also be revealed in response to a mechanicalstimulus.@brown2009@bu2012 For example, fibronectin will dynamicallyunfold and polymerize into fibrils in response to cell-generatedforces.@gee2008@smith2007@oberhauser2002 In contrast, synthetic polymerscommonly weaken or even rupture under force.@kuijpers2004
Inspired by the unfolding triggered crosslinking of proteins likefibronectin, I sought to develop a new method of installingmechanosensitivity within synthetic polymer networks. Recently, wedeveloped organogels@tran2017 and hydrogels@sonu2023 withmechano-responsive properties, both based on preformed diacrylatecrosslinks with reactive pendent thiols for post-polymerizationcrosslinking. Both systems begin as a crosslinked network and respond tocompression, strengthening several hundreds of kPa in elastic modulusover repeated cycles. The mechanosensitivity results from long PEGmolecular shielding groups grafted to the polymer backbone, whichprevent the reactive thiol groups from crosslinking until compressionbrings them together.
To date, the most successful method of creating syntheticmechanosensitive polymers that undergo liquid-to-solid transition is byinserting weak bonds, "mechanophores," within polymer chains that areconverted to an active intermediate in response to force, capable ofstrengthening the material.@ramirez2013@lenhardt2015@hickenboth2007Still other approaches to designing force-sensitive materials involvethe design of small molecules with several ways of participating inintermolecular interactions such as hydrogen bonding, π--π stacking, andvan der Waals forces. Peptide-based isomers functionalized withcholesterol and napthalic groups have been shown to create micellarassemblies that undergo a gel-gel transition with the application ofultrasound.@yu2010 This work, in contrast, uses the shielding groupconcept, starting with uncrosslinked, shielded polymers that can undergoa rapid liquid-to-solid transition upon application of force. Toaccomplish this, graft polymers bearing reactive epoxide@vidil2016groups are mixed with small molecule amine/thiol crosslinkers.Ultrasonic irradiation is used to apply high strain rates to theshielded polymers. Straining of the graft polymers overcomes theirsteric barrier to interaction with the small molecule crosslinkers,facilitating a reaction, that rapidly strengthens the material. Theresultant materials achieve elastic modulus values comparable to ultrahard commercial epoxy coatings. I anticipate that these shieldedpolymers will be useful as extremely hard and solvent-resistant coatingsand as adhesives that can be cured by focusing ultrasound through thesurfaces the adhesive is bound to.
== Materials and methods<materials-and-methods>=== Chemical and polymer sourcing<chemical-and-polymer-sourcing>Materials were purchased from Sigma-Aldrich unless otherwise mentioned.(500 g/mol and 950 g/mol, PEGMA500 and respectively), glycidylmethacrylate (97%, GMA), and 2-methoxyethyl methacrylate (99%, MEMA)were passed through a column of neutral alumina to remove inhibitorsbefore use. 2,2′-(Ethylenedioxy)diethanethiol (95%, EDT), ethylenediamine (99%, EDA), (99%, PPB), (98%, CPA), and2-(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), andacetonitrile (99%, MeCN) were purchased from Fisher Chemical and used asreceived. Basic alumina 60-325 mesh was purchased from Fisher Scientificand used as received.
=== Representative polymer synthesis<representative-polymer-synthesis>Poly(GMA_-co-_PEGMA) and poly(GMA_-co-_MEMA) of all molar ratios and degreeof polymerization (DP) were synthesized by reversibleaddition-fragmentation chain transfer (RAFT) polymerization. Thetargeted 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 gCPA (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 of1,4-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 purgedwith N2 (g) for $tilde.op$20-30 min in an ice bath to prevent solventand monomer evaporation (PEGMA solutions were bubbled in cool water toprevent PEG crystallization). Subsequently, the vial was placed in athermostated aluminum reaction block at 60 °C on top of a magneticstir/hot plate. The reaction was left to stir overnight, yielding aviscous liquid. The solution was removed from heat and exposed to air toterminate the polymerization. The solution was precipitated into cold(-20 °C) ether, the solid washed twice more with cold ether, and driedat 0.01 mbar overnight.
=== Polymer characterization<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 wasdetermined by integration of #super[1]H spectral resonances of the PEGMA/MEMAmethoxy protons and the methanetriyl proton of the GMA glycidyl ring,normalized to the aromatic proton peak at the para position of the CPAphenyl ring, assuming there is one Z group@keddie2012 on every polymerchain.
#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]. ])<fig:MEMAGMANMR>
#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]. ])<fig:GMAPEGMA500NMR>
#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]. ])<fig:GMAPEGMA950NMR>
#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]. ])<fig:GMAPEGMA9506040>
#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]. ])<fig:GMAPEGMA9507030>
#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]. ])<fig:GMAPEGMA5006040>
#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]. ])<fig:GMAPEGMA5007030>
#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]. ])<fig:GMAPEGMA5003070>
#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]. ])<fig:GMAMEMA6040>
#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]. ])<fig:GMAMEMA7030>
=== Copolymer solution preparation<copolymer-solution-preparation>Polymer solutions were initially prepared to be 50 wt% polymer. Forexample, 0.3 g of polymer was dissolved in 0.3 g of solvent, andcrosslinker was added such that the nucleophilic functional group wasequimolar with the total epoxide concentration. To control for theconcentration of crosslinking points in solution, polymers weresubsequently formulated to be 1 M of epoxide in solution. For copolymerscontaining PEGMA2000, solutions were formulated in MeCN at 0.5 M ofepoxide functional units due to the large pendant chains dominating theoverall mass of the sample and crosslinked with EDT catalyzed by LiOH.Each sample was vortexed for 5 sec to ensure complete mixing beforeproceeding with rheometry or sonication.
For all experiments crosslinked with amines, reactions were conducted ina solvent system of 1:1 BuOH:DMF. Alcohols are known to catalyze thereaction between amines and epoxides through the formation of atrimolecular complex.@ehlers2007 Thiol-crosslinked reactions wereconducted in MeCN with 10 µL of 2 M LiOH as a catalyst, necessary todeprotonate the thiols in order to perform a nucleophilic attack on theepoxide ring.@gadwal2015
=== Parallel plate rheology<parallel-plate-rheology>Gelation times and storage moduli ($G'$), and $t a n delta$ of polymersolutions/gels were determined on a Kinexus Pro parallel plate rheometer(Netzsch, Selb, Bayern, Germany). Measurements were run on a 20 mm platewith a 1 mm gap at 1% strain and 1 -- 100 rad s#super[-1] frequencysweep. Each frequency sweep lasted approximately 5 min, and the entiremeasurement lasted approximately 15 hr. The gel point was defined usingthe Winter-Chambon criterion, for which the time of gelation is definedas the point at which $t a n delta$ becomes frequency independent atsmall frequencies.@winter1986@chambon1985@chambon1987 For samples withvery high modulus, the elastic modulus was determined using compressiverheology by taking the slope of the stress strain curve of cured gelswith a 4 mm diameter. Rheological experiments were analyzed using IRISRheo-Hub (IRIS Development, Amherst, MA).@poh2022
=== Sonication-induced gelation of shielded polymers<sonication-induced-gelation-of-shielded-polymers>Polymer solutions were sonicated using a QSonica Q500 with a microtipattachment. The microtip QSonica probe was immersed in a polymersolution in MeCN. Water was flowed across the outer surface of the tubeusing 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 minand 40 s of sonication. Samples were sonicated at 10% amplitude and 20kHz for 5 sec at a time, with 10 sec breaks in between pulses to avoidprobe overheating. Gelation was determined by the point at which thepower output would drop to $tilde.op$0 W and noise from vibrations wouldcease when the polymer had formed a solid gel. Samples were thenimmediately moved to the adjacent needle induced cavitation (NIC) setupto determine the elastic modulus immediately post sonication.
=== Differential scanning calorimetry<differential-scanning-calorimetry>Differential scanning calorimetry (DSC, Q200, TA Instruments) was usedfor crystallization characterization. A sample of (3-5 mg) was sealed ina standard aluminum hermetic pan using TZERO press (TA Instruments)before being added to the calorimeter with an identical empty referencepan. The equipment was lowered to -90 °C and heated to 100 °C at a rateof 5 °C/min to remove the thermal history of the sample. The equipmentwas then lowered to -90 °C again and heated to 100 °C at the same rate,where enthalpy of melting (\$\\Delta H\\textsubscript{m}\$) was obtainedfrom the area of the melting curve divided by the sampleweight.@kong2002 Thermogravimetric analysis (TGA, Q50, TA Instruments)was used to determine the degradation of the samples before running DSCto meet the criteria of a maximum 1.5 wt% loss.
=== Needle induced cavitation<needle-induced-cavitation>Characterization of elastic modulus of sonicated gels was done withneedle induced cavitation (NIC) using a custom-made setup with water asthe fluid, pressurized with a NE 1000 syringe pump (New Era,Farmingdale, NY), contained in a 6 mL disposable syringe with a 27-gaugestainless steel disposable needle, microstand, and Px409-015 GUSBHpressure gauge (Omega, Norwalk, CT). Data collected from NIC wasrecorded on a Surface Mini using a custom LabView program to interfacewith the pressure sensor and record the pressure values (Crosby Lab,University of Massachusetts Amherst, Amherst, MA). When calculating theelastic modulus of gels, the effects of surface tension were ignored andvalues were computed using Equation 1.@dougan2022@barney2020 Each NICexperiment lasted on average from 30-90 sec. $ E = frac(6 P_c, 5) $
== Results and discussion<results-and-discussion>=== Gelation kinetics of polymers under static conditions<gelation-kinetics-of-polymers-under-static-conditions>My goal was to create a polymer network that was shelf-stable and wouldgel in response to force. First, I created a suite of polymers withvarying crosslinker to comonomer ratios. Shielded and control copolymerswere 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 varyingmonomer ratios (30:70 GMA:PEGMA/MEMA to 70:30 GMA:PEGMA/MEMA) and shieldlengths (1, $tilde.op$10, and $tilde.op$20 PEG repeats for MEMA,PEGMA500, and PEGMA950, respectively) to determine their effect ongelation. Additionally, DP for each composition was varied to determinethe effect of polymer length on force sensitivity.
When developing these materials, I imagined a polymer system that wouldbe easily spreadable onto a substrate as a liquid that would thentransition to a solid state after the introduction of mechanicalstimuli. The final solid material should be bonded together permanentlywith covalent crosslinks. To achieve this goal, I selected the monomerGMA for its robust epoxide reactive group. Epoxides are known to undergoa ring-opening reaction in the presence of nucleophiles like amines andthiols. To introduce mechano-sensitivity, I sought to copolymerize myepoxide functional monomers with monomers functionalized with groupsthat could provide steric hindrance. Towards this goal, GMA wasco-polymerized with PEGMA of varied molecular weights from 140 to 950g/mol that I hypothesized could provide a steric hindrance tocrosslinking _via_ their ether side-chains.
Synthesis of this suite of polymers proceeded as expected, with finalDPs and incorporation ratios closely matching the targeted DP and feedratio when conducted in dioxane (@shieldedpolymerstab). Successfulincorporation and molar ratio of constituent monomers was confirmedusing #super[1]H NMR spectroscopy (@fig:MEMAGMANMR - @fig:GMAMEMA7030). DP and incorporation ratiosof poly(GMA_-co-_PEGMA) samples were less consistent compared to theirMEMA counterparts, attributed to the inherent dispersity of PEGMAmacromonomers skewing the actual molar amount added to reactions. Aftersuccessfully synthesizing the desired copolymers, I moved on to assesstheir 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 )<shieldedpolymerstab>For the crosslinkers, I chose EDT due to its non-volatile nature andreasonable stability in air, and EDA as it is commonly used to cureepoxy resins. Amines and thiols were chosen as two candidates bothbecause they are frequently used in commercial epoxy formulations and tocompare the effects of different reaction kinetics on the shieldedcopolymer system. I sought to determine a molecular weight of shieldinggroups that would facilitate delayed crosslinking of the epoxide groupsin the presence of a bifunctional nucleophile without preventing itentirely. In my experiments, I tested a range of effects includingvarying the DP of grafted chains from 1 to 20, varying the DP of thepolymer 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 crosslinkersin 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. ])<fig:shieldinglength>
First, the effect of pendent shield size on crosslinking was assessed atconstant weight percent and static conditions (@fig:shieldinglength b). When solutions are formulated at 50 wt% ofpolymer with EDA, poly(GMA_-co-_MEMA) crosslinks very quickly (1 h) andreaches 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 changein modulus indicating no crosslinking occurred. At constant 50 wt% ofpolymer in solution, the concentration of epoxide for unshielded samples(MEMA) is very high compared to the shielded polymers (PEGMA). At thisfixed concentration, the overall mass for the shielded polymer solutionsis dominated by the presence of ether in the PEGMA side chains, skewingthe sample in favor of unreactive ether and decreasing the number ofpossible crosslinks. The lack of increase in modulus with PEGMA950 maybe due to this ether dominance preventing the formation of avolume-spanning network. Additionally, the relatively large mass of theether side-chains decreases the amount of reactive epoxy in solution.
To control for the effect of variable epoxide concentration, sampleswere next formulated at a constant epoxide molar concentration (@fig:shieldinglength c). Epoxide concentration was set to 1 M, resultingin variable weight percent polymer in solution: control polymer sampleswith low (25%) and shielded samples with high (61%) weight percent. At25 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. Forpoly(GMA_-co-_PEGMA950), wt% changes from 50 to 61 and expectedly showsonly a small increase in $G'$ of 35 Pa. For poly(GMA_-co-_PEGMA500samples, 1 M epoxide concentration is equal to 50 wt% of polymer. Trendsin the effect of shielding groups are the same at constant wt% polymeror mol% epoxides: as the shielding group MW increases, the time togelation and the final modulus both decrease.
Finally, the effect of more reactive nucleophiles on crosslinking wereinvestigated by replacing EDA with EDT and keeping the mol% epoxideconstant (@fig:shieldinglength d). Thiols are known to be strongernucleophiles than primary amines, and the ring opening reaction betweenthiols and epoxides proceeds orders of magnitude faster than betweenamines and epoxides.@t.nguyen2013 At a constant 1 M epoxideconcentration, poly(GMA_-co-_MEMA) with EDT crosslinked more rapidly (30min) than the amine condition and attained a similar final $G'$.Poly(GMA_-co-_PEGMA500) samples crosslinked rapidly (42 min) with EDT, butmore slowly than the MEMA copolymer and attained a final modulus on theorder of 104 Pa. Poly(GMA_-co-_PEGMA950) samples still did not show anysigns of gelation, increasing only to a final modulus of 10 Pa. Evenwith faster reaction kinetics, the PEGMA950 shielding groups suppressgelation.
For permanently crosslinked polymer networks, the equilibrium modulus ofthe cured material can be predicted by Flory's theory of rubberelasticity@flory1941@flory1953 and is proportional to the number ofelastically effective chains in the network.@ferry1980@kulicke1989 Asthe number of elastically effective chains increases, so does theequilibrium modulus; therefore, a low equilibrium modulus implies thepresence of unreacted crosslinks. With the same number of crosslinkspossible in MEMA, PEGMA500, and PEGMA950 samples, and taking theequilibrium modulus of the MEMA polymer in @fig:shieldinglength c,PEGMA500 and PEGMA950 can be inferred to be have a lower crosslinkingdesntiy due to the protective effects of the polyether chains. This ledus to believe that 950 g/mol shielding groups are most effective atcreating a steric barrier to reaction, preventing crosslinking betweenadjacent polymers and resulting in lower final $G'$ values.
=== Controlling gel time through shield graft density<controlling-gel-time-through-shield-graft-density>We next aimed to determine the minimum molar ratio of shielding groupsnecessary to prevent spontaneous crosslinking by varying the ratio ofGMA:PEGMA (@fig:shieldingratio a). I expected that high contentsof shielding monomer would entirely inhibit gelation over themeasurement time, eventually prohibiting crosslinking even under force.To assess the minimum molar ratio necessary for preventing gelationwithout 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 50mol%. Variations in mole percent of MEMA copolymers was assessed as anegative control. The total concentration of epoxides in solutionremained 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. ])<fig:shieldingratio>
In the presence of EDA or EDT with shielding group concentrations at mol50% (PEGMA950), a negligible increase in $G'$ was seen; at 40%, a veryslow increase in $G'$ with a final value on the order of 103 Pa wasdemonstrated; and at 30%, a rapid increase in $G'$ with a final $G'$ of104 Pa (@fig:shieldingratio b-c). At higher shielding monomerpercentages, 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 isthe same.
Next, polymers with PEGMA500 shielding units ($tilde.op$10 repeat units)were varied from 30 to 70 mol% shielding monomer content while keepingthe total epoxide group concentration in solution constant at 1 M(@fig:shieldingratio d) with EDA. When the shielding groupconcentration was 30 and 40 mol%, the material crosslinks rapidly andreaches final $G'$ values on the order of 105 Pa. At 50% concentrationof shielding groups, the material reaches a lower final modulus on theorder of 104 Pa. At the maximum tested 70% molar ratio of shieldinggroup to reactive group, the shielded polymers still form a gel, but donot attain an equilibrium modulus during the experimental timeframe. ThePEGMA500 shielding groups do not provide a sufficient steric barrier toreaction but do provide some hinderance to reaction evidenced by thedecreased final modulus values compared to control samples.
Finally, polymers with one repeat unit pendent chains (MEMA) were variedbetween 30 and 50 mol% control monomer and reacted in the presence ofEDA. Increasing the control monomer ratio from 30 to 50% slightlydecreased to rate at which the material crosslinked and the finalmodulus, from 105 Pa at 30 and 40 mol% control monomer to just above 104Pa at 50 mol% control monomer (@fig:shieldingratio e). Asexpected, the small size of the MEMA comonomer did not contributesignificantly to suppressing the crosslinking kinetics of thecrosslinking polymers.
At low ratios of shielding monomer to reactive monomer, there arestatistically likely to be more stretches of reactive monomer with nosteric effects to prevent them from crosslinking, as well as increasedbackbone flexibility. At high ratios of shielding monomer to reactivemonomer, there are far fewer reactive monomer sequences as well as astraighter backbone due to pendent chains preventing backbone flexing.In summary, only the compositions achieved this with a high degree ofshielding. Gelation was completely inhibited at a 1:1 ratio of reactiveto shielding groups. This composition was selected as the most promisingcandidate for force-activated gelation.
=== Force-induced gelation of shielded polymers<force-induced-gelation-of-shielded-polymers>We hypothesized sonication would be a facile method to mechanicallyinduce gelation of shielded polymer. Sonication can achieve enormousstrain rates approaching 10#super[8] s#super[-1].@hennrich2007 Thisenormous strain rate arises from cavitations introduced duringultrasonic irradiation, nearly instantaneously creating and destroyingmicroscopic bubbles that in turn create pressure gradients able to applyforce through fast solvent flows to polymers of sufficient size. Theforce accumulated along the polymer backbone result in overstretchedregions, which is what is generally accepted to drive conventionalmechanochemical 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. ])<fig:sonication>
Crosslinking of shielded polymers induced #emph[via] sonication wasassessed at DP of 25 to 200 monomer units per chain (@fig:sonication a). Each polymer sample was prepared at 1 M epoxide groupconcentration and reacted with EDT catalyzed by LiOH. Utilizing anultrasonic probe immersed in polymer solutions, samples were subjectedto ultrasonic waves for 5 s at a time, with 10 s of pause in between toprevent probe overheating. All conditions have delayed gelation atstatic conditions, allowing for the characterization of fastercrosslinking with induced strain. At DP equal or greater to 100, samplesgelled within 60 s of sonication time. At 100 DP, I observed a twoorder of magnitude decrease in gelation time when comparing unperturbedsamples with sonicated samples. Samples of DP 150 and 200 gelled morerapidly, within 30 and 20 seconds of sonication time, respectively.Poly(GMA_-co-_PEGMA950) of lower DP (25 and 50) did not show any strainresponsiveness, and the solution boiled before any gelation or viscositychange was observed due to the heat generated by the ultrasonic probe,reaching a temperature of 56 °C measured through an IR thermometer, atwhich point the solution began to boil while sonication was beingapplied. Counterintuitively, the heat generated by sonication iscounterproductive to gelation of this system, possibly due to changes inthe conformation of PEGMA shielding groups at higher temperatures(@fig:shieldedtemp). It is well understood that PEGMA copolymershave a lower critical solution temperature in water that is dependent onthe polyether length and the ionic strength of the environment,@lutz2006but it is not clear that this behavior extends into aprotic organicsolvents. Gelation time under static conditions decreased as a functionof DP like sonicated samples but showed a leveling off after 150 DPunlike the sonicated samples. This decrease in gel time is likely due tothe longer backbone lengths of the polymers beginning closer to thepercolation threshold for gelation, resulting in fewer epoxide-thiolreactions needing to take place to form a volume spanning elastic pathand 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. ])<fig:shieldedtemp>
It has been shown that polymers of sufficient molecular weight aresensitive to shear forces. The large size of polymers results inrestriction of bond angle conformers available due to chain and bondtorsional strain, meaning polymers can accumulate force along theirbackbone as entropic potentialenergy.@wang2013@hermes2011@shi2006@cui2009 High molecular weightpolymers undergo chain scission in response to strong shear forcesgenerating two distinct carbon-centered radicals.@caruso2009@beyer2005These sufficiently strong shear forces result in overstreched segmentsof polymer adjacent to the chain center, generating a tensile force thatdrives mechanochemical reactions.@oneill2023 The chain scission rateincreases with molecular weight.@madras2000 This molecular weightdependence is more accurately described as a polymer lengthdependence.@may2016 It follows that shielded poly(GMA_-co-_PEGMA950) ofsufficient DP is more easily influenced by shear forces in solution ifthe chain length is long enough, surpassing at least 100 units inlength. The increased DP of the polymer also increases the viscosity ofthe sample. Prior literature has shown that highly viscous mediadecreases the effectiveness of ultrasonic micromixing,@monnier1999making it less likely that the dependence of gel time on DP is a resultof mixing phenomena. This study does not elucidate the mechanism forthis system's strain sensitivity. It is not clear what aspect ofcrosslinking is sped up by the application of ultrasound, the additionof EDT to polymer or the addition of polymer+EDT to another polymer.Future studies using mono-thiols functionalized with UV tags would shedlight on the precise molecular mechanism of strain-sensitivecrosslinking.
Cavitation rheology was used to assess post-gelation elastic moduli ofgels formed _via_ sonication (@fig:sonication b). NIC has previouslybeen shown to be effective at extracting elastic modulus informationfrom soft materials.@dougan2022 Sonicated samples were measured to havean elastic modulus near 1 kPa for samples starting at 100 DP, and 20 kPafor samples between 150 and 200 DP as measured by NIC. After a week ofresting in a sealed tube to allow for residual epoxides to be consumedby thiols, the modulus of each sample increased to an average of 20 kPafor samples starting at 100 DP and 60 kPa for samples starting at 150 to200 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 fromcavitation rheology, which tends to have higher variance for sampleswith higher elastic moduli.@zimberlin2007@barney2019 The modulus derivedfrom NIC shows polymers shielded with PEGMA950 cure into relatively weakmaterials.
=== Ultrahard materials from shielded copolymers<ultrahard-materials-from-shielded-copolymers>Conventional epoxy resins and composites can attain $G'$ valuesapproaching and surpassing 10#super[9] Pa.@baral2008@maka2015 Choosingthis value as a benchmark for comparison, I formulatedpoly(GMA_-co-_PEGMA2000) copolymers at a 1:1 monomer ratio and 670 DP. Theextremely long shielding group and long DP were chosen to provide amaterial that had both maximum latency and sensitivity to ultrasound.After sonicating these samples and leaving them to cure for 48 hr, thepolymer crosslinked into an opaque white solid. Samples were prepared as5x4 mm cylinders, and their moduli were assessed on a rheometer viacompression with a 4 mm diameter plate. An elastic modulus value of 62MPa was extracted from the resultant stress-strain curve (@fig:ultrahardshield a), approaching that of conventional epoxymaterials. Immersing gels of this copolymer into acetone and ethanolshowed no visible change in the material, but in MeCN, DCM, and waterthe gels crumbled into insoluble chunks (@fig:ultrahardshield b),leading me to conclude that the material's strength comes from acombination of epoxide-thiol covalent crosslinks and PEG side chaincrystallization. It is well known that graft copolymers withcrystallizable side chains will form crystaldomains.@takeshita2010@inomata2005 Using DSC I was able to measure amelting temperature for a cured GMA:PEGMA2000 sample. confirming thematerial is partially crystallized (@fig:dsc). Using a stericshielding approach, I created an ultrahard material through anunexpected 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. ])<fig:ultrahardshield>
#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. ])<fig:dsc>
== Conclusion<conclusion>We synthesized novel strain-sensitive shielded polymers containing bothreactive epoxides and molecular shields. These shielding PEG chainsprovide a steric barrier to an otherwise powerful and efficientcrosslinking reaction between amines or thiols and epoxides. Thisapproach to creating strain sensitive materials provides a facile routeto creating strain responsive coatings and adhesives, using well-knownand commercially available monomers. Through this I demonstrated, forthe first time, a liquid-to-solid transition accelerated under forceusing shielded reactive polymers. I showed that force stimulatedgelation could be achieved with ultrasound. I further showed thatsteric shielding can create ultrahard materials. Suppressed gelationwithout force, combined with ultrasound sensitivity, make this polymeran ideal candidate for an adhesive in a heat or light sensitiveapplication.
#emph[The work in this chapter represents a collaboration with JichaoSong and Professor Jessica Schiffman from the Chemical EngineeringDepartment at University of Massachusetts Amherst. DSC measurements in@fig:dsc were conducted and data analyzed by Jichao Song. NICdata was collected and analyzed by Hsu Shwe Yee Naing.]