Cascade Mechanochemical Transformation of a Benzobarrelane Polymer: A Neighboring Repeat Unit Effect

Cascade Mechanochemical Transformation of a Benzobarrelane Polymer: A Neighboring Repeat Unit Effect | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Cascade Mechanochemical Transformation of a Benzobarrelane Polymer: A Neighboring Repeat Unit Effect Yan Xia, Daniel Lee, Rui Xu, Erica Flear, Ke Zheng, Soren Holm, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7133429/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Mechanical force can trigger non-destructive chemical transformations of force-responsive molecules, mechanophores, that are embedded in a long polymer chain to change or induce a variety of their physical and chemical properties. Studies on polymer mechanochemistry have thus far focused on the design and understanding of the reactivity of individual mechanophores. However, when mechanophores, or even molecular structures that are not typically considered force-responsive, are coupled with each other in the polymer backbone, new reactivity and force response that are absent from discrete molecules may arise to transform polymer backbone structures. Herein, we describe a system where mechanically triggered backbone bond scission generates biradical intermediates, which then undergo radical cascade reactions to transform polymer backbone structure. Our design is based on a polymer with benzobarrelane repeat units that are connected via backbone alkenes. The alkene linkage is crucial for the radical cascade ring-opening reactions to occur across multiple connected benzobarrelane units. In contrast, no mechanochemical reaction was observed in isolated benzobarrelane units that are separated by alkyl linkages, even when the alkenyl substituents of benzobarrelane were preserved. Despite the lack of weak covalent bonds or significant ring strain in the benzobarrelane polymer, it achieved similar degrees of mechanochemical transformation as our previously reported polyladderene systems consisting of repeat units of highly strained fused cyclobutanes. Ab initio steered molecular dynamics and force-modified potential energy surface calculations supported the force-induced radical cascade mechanism along the polymer backbone. Simulations indicated a strong preference for sequential mechanoactivation: upon ring-opening of one benzobarrelane unit, its immediately neighboring unit is most likely to be activated next. This work demonstrates a new strategy for designing mechanically responsive polymers by creating chemical pathways to promote cooperative mechanoactivation across neighboring units. It further underscores the potential to elicit novel reactivities through the collective interaction of otherwise inert individual molecules. Physical sciences/Chemistry/Polymer chemistry/Polymer synthesis Physical sciences/Chemistry/Organic chemistry/Reaction mechanisms Physical sciences/Chemistry/Theoretical chemistry/Reaction mechanisms Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction When a polymer backbone experiences stress above a threshold, scission of chemical bonds occurs, leading to chain cleavage. 1-2 By incorporating designed force-responsive molecules, mechanophores, into polymer backbones, non-destructive molecular transformations can be harnessed to sense and respond to stress or advance our understanding of force-induced reactivity. 3-7 Since the advent of polymer mechanochemistry, many mechanophores have been reported that show mechanochemical reactivities different from thermal or photochemical pathways, 8-11 change absorption or emission properties, 12-16 release small molecules, 17-19 or transform from nonconjugated to conjugated structures. 20-22 The vast majority of designs and studies in polymer mechanochemistry are focused on isolated mechanophores, either centered in a long polymer chain or multiple mechanophore molecules being connected through long alkyl linkages in the polymer backbone. 23 Interesting scenarios can emerge when mechanophores are electronically coupled. For example, mechanochemical study of a fused bis-rhodamine structure showed cooperative reactivity. 24 Only the doubly ring-opened product was observed upon sonication, because the electronics of the singly ring-opened structure accelerates the second ring-opening event. In ladderane structures consisting of multiple fused cyclobutane rings, we discovered strong dynamic effects in their mechanochemical unzipping. 25 The first mechanochemical cycloreversion event accelerates the rate of subsequent cycloreversion, leading to ‘all-or-none’ unzipping of a ladderane. Gem -difluorocyclopropane has been found to undergo reversible mechanochemical ring-opening to generate a biradical intermediate, which quickly recombines to regenerate gem -difluorocyclopropane upon removal of force. 9 However, incidental reactivity has been observed when two difluorocyclopropane units were connected through one ethylene linkage in a polymer chain. The mechanically generated radicals from two adjacent difluorocyclopropane units combined to cleave the polymer chain leaving alkene chain ends. 26 Without electronic coupling or chemical pathways, isolated mechanophores may not be expected for synergistic reactivity even when tethered together. We have recently developed a family of multicyclic mechanophores that can be directly polymerized via ring-opening metathesis polymerization (ROMP), generating polymechanophores with every mechanophore repeat unit connected via a backbone alkene. 20-22, 27 In our past polymechanophore systems, strained rings, particularly fused cyclobutanes, were leveraged to induce mechanochemical reactivity of the repeat unit. We hypothesized that, in the absence of significant ring strain or other reaction pathways within the same mechanophore unit, the mechanochemically generated radicals, stabilized by backbone alkenyl linkages, may undergo reaction pathways across the polymer backbone. Thus, new types of polymechanophore systems may be envisioned where chemical coupling between appropriately connected individual repeat units can allow cascade chemical reactivity across multiple units, but such mechanochemical reactivity may be absent from an isolated individual unit. Contemplating the above hypothesis, we designed a polymer system with benzobarrelane (or dihydro-benzobarrelene) repeat units connected by backbone alkenes ( Fig. 1 ). The rationale for choosing a benzobarrelane motif as the repeat unit is based on the following considerations. First, the benzobarrelane scaffold is thermally stable with a low ring strain, and it is not intuitively considered as a potential mechanophore. Second, among the three types of C–C bonds in the polymer backbone, the C(sp 3 )–C(sp 3 ) bond of benzobarrelane repeat unit is deemed the weakest compared to the other two types of bonds, which are C(sp 2 )=C(sp 2 ) and C(sp 2 )–C(sp 3 ) bonds, and thus may be preferentially cleaved. Third, the benzene moieties in benzobarrelane are periplanar with the benzylic C–H bonds, thus cannot provide stabilization of benzylic radicals. Therefore, the mechanochemically generated biradicals would preferably migrate along the backbone rather than undergo a shift down to the benzobarrelane bridgehead positions. Results and Discussion We envisioned that the desired poly(alkenyl benzobarrelane) can be accessed via ROMP of a cyclobutene-fused benzobarrelane 1 . We synthesized 1 from Diels-Alder reaction between anthracene and maleic anhydride followed by a sequence of high yielding reactions that we have previously used to install fused cyclobutene rings ( Fig. 2 ). 20 Attempted ROMP of 1 in toluene at room temperature resulted in no conversion, presumably due to the steric hindrance around the cyclobutene. Elevating the temperature to 60 °C gave complete conversion after 20 h, reaching degrees of polymerization (DP) of 1000. Size exclusion chromatography (SEC) with multiangle light scattering (MALS) analysis of resulting poly1 revealed very low dispersity <1.05 and measured M n = 226 kDa in excellent agreement with the theoretical molecular weight (MW), even with the slow-initiating Grubbs II catalyst. The good control of MW distribution in ROMP of 1 using a slow initiator suggested slow propagation of 1 and negligible chain transfer in poly1 . In our previous designs of polymechanophores, at least one strained cyclobutane is present in the repeat unit along the backbone. 20-22, 27-28 The strain release upon cycloreversion of cyclobutane provides the driving force for efficient mechanoactivation. In contrast to cyclobutane, benzobarrelane has a low ring strain energy of 9.7 kcal/mol ( SI S6.4 ), and therefore we were curious about its mechanochemical reactivity. We subjected poly1 with DP = 1000 at a concentration of 1 mg/mL in THF to sonication using a typical sonochemical protocol. 29 SEC analysis of the sonicated polymer at different time points showed that the original polymer peak significantly decreased within 1 h and disappeared in 2 h, accompanying the appearance of a broader, lower MW peak ( Fig. 3b ). This evolution of SEC profile is commonly observed from sonochemical mechanoactivation of narrow-disperse polymers, due to nonselective main chain cleavage. 8, 22, 29 1 H NMR analysis of the sonicated poly1 showed the emergence of multiple new broad signals between 7 and 4.5 ppm. The new signals in 7.5-6.5 and 5.5-4.5 ppm regions overlapped with the backbone alkene and aromatic signals of pristine poly1 ( Fig. 3d ). After subtracting the signals of pristine poly1 , the integration of the newly generated signals in the regions of 7.5-6.5, 6.5-5.5, and 5.5-4.5 ppm gave a 1:1:1 ratio, and their intensity corresponded to the decrease in intensity of the original poly1 signals. We hypothesized that the backbone alkenes allow resonance of allylic biradicals generated upon the mechanochemical cleavage of the backbone C(sp 3 )–C(sp 3 ) bond in a benzobarrelane unit. This resonance facilitates fragmentation of the backbone C(sp 3 )–C(sp 3 ) bond in the immediately adjacent benzobarrelane units, thus providing a mechanism for radical propagation along the polymer backbone to neighboring units. As such, the repeat unit of the transformed polymer would consist of a dihydroanthracene resulting from the ring-opening of benzobarrelane and a conjugated diene ( Fig. 3a ). We suspected the newly formed diene to be susceptible to cross metathesis, while the backbone alkenes in original poly1 are inert to cross metathesis due to steric hindrance as indicated by the very low dispersity of poly1 . Thus, we subjected poly1 and sonicated poly1 to excess Z -hex-3-ene and Hoveyda-Grubbs II catalyst at 60 °C. Indeed, the SEC trace of poly1 remained unchanged, but that of the sonicated poly1 shifted to lower MW ( Fig. 3c ). For sonicated poly1 , the high MW peak corresponding to uncleaved polymer significantly decreased its intensity after cross metathesis, suggesting that mechanoactivation occurred in polymer strands that did not undergo chain cleavage. To assign the NMR signals of mechanochemically transformed polymer, we sought to synthesize a model compound representing its expected constituent structure, syn -dibutadienyl-dihydroanthracene, which is not reported in literature. In our initial attempts, we synthesized syn -di(bromovinyl)-dihydroanthracene, which was subjected to various cross coupling conditions to generate the desired dibutadienyl substitution, but led to complex inseparable mixtures ( Scheme S1 ). We speculated that the acidic protons in dihydroanthracene interfered with the cross coupling reaction. We then sought to replace the problematic acidic protons in dihydroanthracene with methyl substituents. Indeed, the dimethyl derivative underwent smooth Stille coupling with a vinyl tin species to give syn -9,10-dimethyl-9,10-dienyl-9,10-dihydroanthracene ( Scheme S2 ). We synthesized this reference structure with Z , E or E , E configurations for the dienyl substituents. NMR spectra of these compounds showed alkenyl signals from the dienes in the range of 5.5-6.0 ppm for Z , E and 5.7-6.5 ppm for E , E isomer (see SI S2.2 ), thus allowing us to assign the emergent signals in sonicated poly1 in 5.5-6.5 ppm and 6.5-7 ppm regions to the mechanochemically generated backbone dienes. The benzylic protons in dihydroanthracene were assigned to the signals in the 4.5-5.5 ppm region based on literature examples. 30 Due to the overlapping 1 H NMR signals of pristine and mechanoactivated poly1 , we subtracted the alkene signals from the unreacted poly1 to use the newly generated diene signals to calculate the percentage of mechanoactivation (see SI S4 ) for details of the analysis). As such, we quantified that 36% of the benzobarrelane repeat units were converted to dialkenyl dihydro-anthracene in 150 min of sonication ( Fig. 3d ). This extent of mechanoactivation is indeed similar to what we have observed in our previous polymechanophore systems containing strained cyclobutane repeat units at the same duration of sonication. 21-22 We next probed the structural features necessary for the observed mechanochemical transformation using control polymers ( Fig. 4 ). Based on our postulated radical cascade mechanism, backbone alkene linkages connecting the benzobarrelane repeat units are required to migrate the radicals to the neighboring units. Hydrogenating the backbone alkenes should thus prevent this pathway. Indeed, the hydrogenated poly1 showed no discernable change in its NMR spectrum upon prolonged sonication ( Fig. S2 ). Alkenyl substituents are known to lower the threshold force for mechanochemical ring-opening of cyclobutene compared to alkyl substituents, due to the stabilization of the biradical intermediate upon C–C bond cleavage. 31 To ensure that the absence of structural changes is not due to increased threshold force for mechanoactivation, we designed another control polymer, where the dialkenyl backbone linkage to benzobarrelane is preserved but the neighboring benzobarrelane units are distanced by an alkyl spacer. We found that 1 and 2,3-dihydrofuran (DHF), a comonomer that we previously reported to greatly suppress homoaddition of norbornenes, 32 can undergo truly random copolymerization at 40 °C in toluene. The 1 H NMR spectrum of the isolated polymer revealed equal composition of 1 and DHF, and its 1 H and 13 C NMR spectra showed no signals corresponding to the homodyads of 1 or DHF ( Fig. S3 ). SEC-MALS analysis showed M n = 148 kDa, corresponding to ~500 units of ring-opened 1 and DHF combined. Computed contour lengths of a ring-opened 1 -DHF hetero-dyad and a homo-dyad of 1 are 8.5 and 6.4 Å, respectively ( Fig. S19 ), thus the synthesized poly(1- co -DHF) had a greater contour length than the studied poly1 , and would be expected to experience sufficiently high forces during sonication as for poly1 . Nevertheless, sonication of poly(1- co -DHF) under the same conditions as for poly1 did not yield any new detectable NMR signals. We wondered if biradical species might be generated transiently from the benzobarrelane structure in poly(1- co -DHF) , so we attempted sonication in the presence of potent radical trapping or hydrogen transfer agents. However, even sonicating poly(1- co -DHF) in the presence of a large excess of 1,4-cyclohexadiene or tetracyanoethylene, gave no change in 1 H NMR signals ( Fig. S4 ). We rationalized that even though poly(1- co -DHF) might give rise to ring-opening of a benzobarrelane unit, the transiently generated biradical species cannot effectively migrate in the absence of a chemically coupled neighboring benzobarrelane unit. Thus, any mechanochemically generated biradicals within a benzobarrelane unit would spontaneously recombine upon removal of force. We used calculation to further understand the mechanism of this polymeric mechanochemical transformation. We first used ab initio steered molecular dynamics (AISMD) 33 to simulate the dynamics of mechanoactivation of a computationally manageable tetramer system ( Fig. 5a ), using the unrestricted B3LYP density functional on a 6-31G* basis set with Grimme’s third generation empirical dispersion 34 (at UB3LYP-D3/6-31G* level of theory). 30 AISMD simulations were performed under an external pulling force f = 2.5 nN for a total run time of 5 ps in each simulation ( SI S6.2 for details). The AISMD simulations showed that the radical cascade can be initiated by bond cleavage from any benzobarrelane unit, but more often from an internal unit. The cascade ring-opening can be represented by plotting scissile bond length over simulation time ( Fig. 5b ). In an exemplary simulation, the first bond cleavage occurs at the C 3 –C 4 bond (atomic indices in Fig. 5a ), followed by cleavage of C 5 –C 6 , C 7 –C 8 , and lastly C 1 –C 2 bond ( Fig. 5b ). Upon mechanoactivation, the first C–C bond cleavage forms biradicals, which subsequently fragment the C–C bond of the adjacent benzobarrelane unit, leading to the formation of a conjugated diene between ring-opened repeat units. The biradical cascade can be analyzed using Mulliken atomic spin density 35 values during the AISMD simulation to visualize radical migration along the backbone bonds. In Fig. 5c , upon the C 3 –C 4 bond cleavage, biradicals are formed at C 3 and C 4 positions as their spin density values quickly spiked to +1 and –1. Immediately after the bond cleavage, the biradicals on C 3 and C 4 delocalize within bridging conjugated dienes B 23 and B 45 , respectively. Subsequently, the biradicals start to migrate in opposite directions along the backbone. The free radical on B 45 traverses through the unit of B 67 , and then locates on the end diene E 8 , while the other radical on B 23 traverses to the other end diene E 1 . After about 3 ps simulation, the spin densities are distributed only at the two ends of the fully ring-opened tetramer, with no spin densities found in the formed internal dienes connecting the ring-opened benzobarrelane units. All the AISMD simulations showed that after the first bond is mechanochemically cleaved in the tetramer, the generated biradicals migrate along the backbone bonds connecting the benzobarrelane units, and eventually locate at the end of the ring-opened product. Furthermore, the simulation indicated a strong preference for sequential mechanoactivation. Out of a total of 30 simulations, 26 showed that upon ring-opening of one benzobarrelane unit, its immediately connected or neighboring unit is activated next. Only 4 out of 30 simulations showed that the subsequent mechanoactivation is from a non-neighboring unit after the first mechanoactivation ( Table S3 and Fig. S6 ). This observation suggested a sequential cascade and cooperative mechanoactivation behavior for the investigated polymer system. Additionally, we investigated the electronic structures and kinetics of the radical cascade reaction under applied forces by calculating the force-modified potential energy surface (FMPES). 33 We focused on the mechanoactivation of dimeric structure 2 , which is the minimum necessary structure for probing the mechanism and the formation of biradical intermediate 3 and mechanochemical product 4 ( Fig. 6a ). We calculated FMPES at force levels from 0.5 to 2.5 nN using the same UB3LYP-D3/6-31G* level of theory ( SI S6.3 for details). Two critical reaction steps were found during the minimum energy path (MEP) optimization on the FMPES: the first bond cleavage in 2 to form biradical intermediate 3 , and the second bond cleavage of the neighboring unit in 3 to form product 4 with a diene linkage. For both reaction steps, as the external force is increased, the activation energies are lowered with the transition state occurring earlier towards the reactant ( Fig. 6b ). Furthermore, under the same external force, barrier heights of the two reaction steps were found to be similar, which could imply similar rates of C–C bond cleavage. Electron density distribution on the molecular orbitals (SOMO 1 and SOMO 2 ) of the critical geometries also supported the mechanism of radical cascade mechanoactivation ( Fig. 6c ). The transition state of the first ring-opening reaction TS 2-3 involves s -bond cleavage that creates the biradical intermediate 3 . In the second ring-opening transition state structure TS 3-4 , the biradicals migrate in opposite directions through p-orbitals. In product 4 , the electrons are localized at the two terminal dienes ( Fig. 6c ). Beyond the presented MEPs under forces, microkinetic modeling was performed considering all critical geometries, transition states, and rate constants for all possible reaction steps in this dimeric system ( Fig. S11 ). The results showed that as the external force is raised by each 0.5 nN increment, the time scale for ring-opening lowers dramatically by four to five orders of magnitude ( Fig. S12 ). Furthermore, as the force is increased, intermediate 3 is significantly stabilized with a much longer lifetime ( Fig. S12 ). Under experimental conditions, the biradical product 4 is likely susceptible to hydrogen abstraction in solution to become closed-shell species. Conclusion We have designed a polymechanophore system with benzobarrelane repeat units connected by backbone alkenes via living polymerization of a cyclobutene-fused benzobarrelane. Upon sonication, polybenzobarrelane was transformed into dihydroanthracene repeat units connected by dienes via a radical cascade mechanism. Despite the assumed low mechanochemical reactivity of benzobarrelane, the achievable degrees of mechanoactivation are similar to those in our previously reported polymechanophore systems consisting of highly strained structures in repeat units. Uniquely, isolated benzobarrelane that is not connected with another benzobarrelane via an alkene linkage did not give any detectable products under the same sonication conditions. Ab initio steered molecular dynamics and electronic structure calculations of the mechanoactivation of this polymechanophore system supported the radical cascade mechanism, where mechanochemically generated radicals from ring-opening of one benzobarrelane unit propagate along the polymer backbone to ring open neighboring units. The described system is unique in that its mechanochemical reactivity is observed only when neighboring repeat units are coupled through a viable path for cascade radical reactions, but is absent from isolated individual units. New opportunities in polymer mechanochemistry emerge as we shift the focus from considering the reactivity of individual molecular structures to designing polymeric scaffolds that exhibit mechanically induced cascade reactivities to rearrange polymer backbones. More broadly, novel reactivities of polymeric scaffolds may be elicited by enabling chemical coupling or collective interactions of otherwise inert individual molecules. We envision the possibility of mechanically initiating reactions that can propagate along the polymer chain, leading to amplified mechanochemical response of macromolecular systems. Declarations Author Contribution ‡ These authors contributed equally to this work. Acknowledgement This work was supported by the U.S. Army Research Office under grant number W911NF2420055 and the National Science Foundation under award number 2350170. 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S., Electronic population analysis on LCAO–MO molecular wave functions. I. J. Chem. Phys. 1955, 23 (10), 1833-1840. Additional Declarations There is NO Competing Interest. Supplementary Files barrelanesupportinginfoFinal.pdf SUPPLEMENTARY INFORMATION for publication Movie1TetramerAISMDRun8Fig4.mp4 Tetramer_AISMD_Run8_Fig4 Movie2TetramerAISMDRun2FigS7.mp4 Movie2_Tetramer_AISMD_Run2_FigS7 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Xia","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyklEQVRIiWNgGAWjYLCCDyCC+QADAw8DA2MDMToYZzAYMDCwJZCghZmHJC0Gx88ek7b580fenI352Ic3DDayGw4Q0nImL9k4t83AcGcbW/LMOQxpxoS1HMgxfJzbYMC44X6PMdCFhxMJazn/xuCwxR8D+w3HeEBa/hOh5QbQFgY2g0SolgOEtUjeeGNs2NtmnLzhGFsy4xyDZOOZhLTwnc8xk/jxR852wzHmwwxvKuxk+whpUUBVYEBAOQjINxChaBSMglEwCkY4AAACJkN36uuiSQAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-5298-748X","institution":"Stanford University","correspondingAuthor":true,"prefix":"","firstName":"Yan","middleName":"","lastName":"Xia","suffix":""},{"id":486299731,"identity":"fd439ffc-c109-4703-989d-93668c9caf19","order_by":1,"name":"Daniel Lee","email":"","orcid":"","institution":"Stanford University","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Lee","suffix":""},{"id":486299732,"identity":"d3064b32-0d7e-47af-97e5-8c6aded5fdbb","order_by":2,"name":"Rui Xu","email":"","orcid":"https://orcid.org/0000-0003-3264-9050","institution":"Stanford University","correspondingAuthor":false,"prefix":"","firstName":"Rui","middleName":"","lastName":"Xu","suffix":""},{"id":486299733,"identity":"23ce1cd7-5c7d-4225-94fb-1838796d1ae9","order_by":3,"name":"Erica Flear","email":"","orcid":"","institution":"Stanford University","correspondingAuthor":false,"prefix":"","firstName":"Erica","middleName":"","lastName":"Flear","suffix":""},{"id":486299734,"identity":"563f0207-aa22-41de-94b2-dd4ac49a65f7","order_by":4,"name":"Ke Zheng","email":"","orcid":"","institution":"Stanford University","correspondingAuthor":false,"prefix":"","firstName":"Ke","middleName":"","lastName":"Zheng","suffix":""},{"id":486299735,"identity":"3cfb4075-b2d9-4d20-94a5-6b04244663e6","order_by":5,"name":"Soren Holm","email":"","orcid":"","institution":"Stanford University","correspondingAuthor":false,"prefix":"","firstName":"Soren","middleName":"","lastName":"Holm","suffix":""},{"id":486299736,"identity":"3ce64a77-d284-4c8d-97f5-fc70a76dd0bb","order_by":6,"name":"Diptarka Hait","email":"","orcid":"https://orcid.org/0000-0003-1570-920X","institution":"Stanford University","correspondingAuthor":false,"prefix":"","firstName":"Diptarka","middleName":"","lastName":"Hait","suffix":""},{"id":486299737,"identity":"a1514cee-458b-4932-8d01-30e8349a3371","order_by":7,"name":"Todd Martínez","email":"","orcid":"","institution":"Stanford University","correspondingAuthor":false,"prefix":"","firstName":"Todd","middleName":"","lastName":"Martínez","suffix":""}],"badges":[],"createdAt":"2025-07-15 18:40:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7133429/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7133429/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87297853,"identity":"c066870c-9076-4010-ad89-851304913b51","added_by":"auto","created_at":"2025-07-22 12:49:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":115953,"visible":true,"origin":"","legend":"\u003cp\u003eMechanically triggered polymer backbone transformation via radical cascade reactions across neighboring repeat units.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7133429/v1/b6b47e8f728da89f0a6b1aeb.png"},{"id":87299438,"identity":"31ad1b35-fc5d-4b10-b210-bf449720831d","added_by":"auto","created_at":"2025-07-22 13:05:51","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":218228,"visible":true,"origin":"","legend":"\u003cp\u003eSynthesis of benzobarrelane \u003cstrong\u003e1 \u003c/strong\u003eand its polymer\u003cstrong\u003e poly1\u003c/strong\u003e.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7133429/v1/51ee9f10ff0a487cd8580d15.png"},{"id":87299183,"identity":"e98f5b8e-030d-41e2-b054-f60dda044be8","added_by":"auto","created_at":"2025-07-22 12:57:51","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":834926,"visible":true,"origin":"","legend":"\u003cp\u003eMechanochemical transformation of \u003cstrong\u003epoly1\u003c/strong\u003e. \u003cstrong\u003e(a)\u003c/strong\u003e Proposed mechanism for mechanochemical transformation of \u003cstrong\u003epoly1\u003c/strong\u003e. \u003cstrong\u003e(b)\u003c/strong\u003e GPC traces tracking the change in molecular weight as a function of sonication time. \u003cstrong\u003e(c)\u003c/strong\u003e Overlaid GPC traces of \u003cstrong\u003epoly1\u003c/strong\u003e after 60 min sonication (solid black line) and after the cross metathesis (CM) deconstruction (blue dashed line), and original\u003cstrong\u003e poly1\u003c/strong\u003e after being subjected to the same metathesis conditions (red dashed line). \u003cstrong\u003e(d)\u003c/strong\u003e Stacked partial \u003csup\u003e1\u003c/sup\u003eH NMR spectra of \u003cstrong\u003epoly1\u003c/strong\u003e before (top) and after (bottom) sonication.\u003cstrong\u003e (e)\u003c/strong\u003e Degree of mechanoactivation (red circle, left \u003cem\u003ey\u003c/em\u003e-axis) and polymer molecular weight (blue diamond, right \u003cem\u003ey\u003c/em\u003e-axis) as a function of sonication time.\u0026nbsp;\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7133429/v1/deb8a70c2c839dd0153966ee.png"},{"id":87299182,"identity":"616c14e4-068a-4276-82bd-c5b9582ab67d","added_by":"auto","created_at":"2025-07-22 12:57:51","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":110925,"visible":true,"origin":"","legend":"\u003cp\u003eSynthesis of control polymers, hydrogenated \u003cstrong\u003epoly1\u003c/strong\u003e and random copolymer of \u003cstrong\u003e1\u003c/strong\u003e and \u003cstrong\u003eDHF\u003c/strong\u003e, which showed no observable mechanochemical reaction under the same sonication conditions.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7133429/v1/6f7396b36a55b8bb6c35e516.png"},{"id":87297855,"identity":"2f1fbbea-d7d0-4f39-b56e-b43b23b9a905","added_by":"auto","created_at":"2025-07-22 12:49:51","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1387218,"visible":true,"origin":"","legend":"\u003cp\u003eComputational observation of mechanochemical ring-opening of a tetramer of \u003cstrong\u003e1\u003c/strong\u003e and radical cascade dynamics using the \u003cem\u003eab initio\u003c/em\u003e steered molecular dynamics (AISMD) simulation at UB3LYP-D3/6-31G* level of theory. \u003cstrong\u003e(a)\u003c/strong\u003e The structure of a fully ring-opening tetramer. Labels include indices of carbon atoms in the four cleaving bonds and their bond lengths (\u003cem\u003er\u003c/em\u003e\u003csub\u003eij\u003c/sub\u003e), dienes at the ends of tetramer (E\u003csub\u003ek\u003c/sub\u003e), and bridging dienes between two benzobarrelane units (B\u003csub\u003e\u003cem\u003emn\u003c/em\u003e\u003c/sub\u003e). \u003cstrong\u003e(b)\u003c/strong\u003e Evolution of bond lengths for the four cleaving bonds (\u003cem\u003er\u003c/em\u003e\u003csub\u003e12\u003c/sub\u003e, \u003cem\u003er\u003c/em\u003e\u003csub\u003e34\u003c/sub\u003e, \u003cem\u003er\u003c/em\u003e\u003csub\u003e56\u003c/sub\u003e, and \u003cem\u003er\u003c/em\u003e\u003csub\u003e78\u003c/sub\u003e). (\u003cstrong\u003ec\u003c/strong\u003e) Evolution of the sum of atomic spin density values at all conjugated dienes, S\u003cem\u003eρ\u003c/em\u003e(E\u003csub\u003e\u003cem\u003ek\u003c/em\u003e\u003c/sub\u003e) and S\u003cem\u003eρ\u003c/em\u003e(B\u003csub\u003e\u003cem\u003emn\u003c/em\u003e\u003c/sub\u003e). \u003cstrong\u003eE\u003c/strong\u003e denotes dienes at the ends of tetramer, and \u003cstrong\u003eB\u003c/strong\u003e denotes bridging dienes between two benzobarrelane units.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-7133429/v1/88f08c9a5642d0077cacba0c.png"},{"id":87297858,"identity":"b4bc0a40-5da0-4c8c-910a-1ebb8d236f33","added_by":"auto","created_at":"2025-07-22 12:49:51","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":987519,"visible":true,"origin":"","legend":"\u003cp\u003eCalculated energies and electronic structures from force-modified potential energy surface (FMPES) of a dimeric structure \u003cstrong\u003e2\u003c/strong\u003e (at UB3LYP-D3/6-31G* level of theory). \u003cstrong\u003e(a)\u003c/strong\u003e Reaction mechanism.\u003cstrong\u003e (b)\u003c/strong\u003e Force modified minimum energy paths (MEPs) calculated at 0.5, 1.0, 1.5, 2.0, and 2.5 nN forces. Left panel: MEPs for the first bond cleavage in dimer \u003cstrong\u003e2\u003c/strong\u003e to form intermediate \u003cstrong\u003e3\u003c/strong\u003e. Right panel: MEPs for the second bond cleavage from the intermediate \u003cstrong\u003e3 \u003c/strong\u003eto product \u003cstrong\u003e4\u003c/strong\u003e. \u003cstrong\u003e(c)\u003c/strong\u003e Natural orbital contours of two singly occupied molecular orbitals (SOMOs) of \u003cstrong\u003eTS\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2-3\u003c/strong\u003e\u003c/sub\u003e, \u003cstrong\u003eTS\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e3-4\u003c/strong\u003e\u003c/sub\u003e, and \u003cstrong\u003e4\u003c/strong\u003e at \u003cem\u003ef\u003c/em\u003e = 2.0 force. The orbitals are computed with single-point energy calculations at CAS(2,2)SCF/6-31G* level of theory. Occupation numbers (average number of electrons occupying the molecular orbital) are shown at the bottom of each orbital. All the natural orbital contours are included in \u003cstrong\u003eSI Fig. S13-17\u003c/strong\u003e.\u0026nbsp;\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-7133429/v1/779d10930e8bf1a34ca7149c.png"},{"id":89073662,"identity":"129a9408-6905-4263-8e0f-c84b236fcdde","added_by":"auto","created_at":"2025-08-14 11:40:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4602528,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7133429/v1/4bd09373-54cd-4732-9419-10b4f3367acd.pdf"},{"id":87297860,"identity":"3df811b7-953d-439b-9f59-b550eb1d955b","added_by":"auto","created_at":"2025-07-22 12:49:51","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":8172968,"visible":true,"origin":"","legend":"SUPPLEMENTARY INFORMATION for publication","description":"","filename":"barrelanesupportinginfoFinal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7133429/v1/209e07d9bb42da9958e64fe4.pdf"},{"id":87297861,"identity":"57746817-bcc9-4b8c-b9f7-389ce00f7167","added_by":"auto","created_at":"2025-07-22 12:49:51","extension":"mp4","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":21770424,"visible":true,"origin":"","legend":"Tetramer_AISMD_Run8_Fig4","description":"","filename":"Movie1TetramerAISMDRun8Fig4.mp4","url":"https://assets-eu.researchsquare.com/files/rs-7133429/v1/6e291103ce50b4acf26e4d64.mp4"},{"id":87297862,"identity":"38eb5cb0-855d-4758-9a60-9c5f369184a9","added_by":"auto","created_at":"2025-07-22 12:49:51","extension":"mp4","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":21946440,"visible":true,"origin":"","legend":"Movie2_Tetramer_AISMD_Run2_FigS7","description":"","filename":"Movie2TetramerAISMDRun2FigS7.mp4","url":"https://assets-eu.researchsquare.com/files/rs-7133429/v1/2804664f6fbd5450433d5aef.mp4"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Cascade Mechanochemical Transformation of a Benzobarrelane Polymer: A Neighboring Repeat Unit Effect","fulltext":[{"header":"Introduction","content":"\u003cp\u003eWhen a polymer backbone experiences stress above a threshold, scission of chemical bonds occurs, leading to chain cleavage.\u003csup\u003e1-2\u003c/sup\u003e By incorporating designed force-responsive molecules, \u0026nbsp; mechanophores, into polymer backbones, non-destructive molecular transformations can be harnessed to sense and respond to stress or advance our understanding of force-induced reactivity.\u003csup\u003e3-7\u003c/sup\u003e Since the advent of polymer mechanochemistry, many mechanophores have been reported that show mechanochemical reactivities different from thermal or photochemical pathways,\u003csup\u003e8-11\u003c/sup\u003e change absorption or emission properties,\u003csup\u003e12-16\u003c/sup\u003e release small molecules,\u003csup\u003e17-19\u003c/sup\u003e or transform from nonconjugated to conjugated structures.\u003csup\u003e20-22\u003c/sup\u003e The vast majority of designs and studies in polymer mechanochemistry are focused on isolated mechanophores, either centered in a long polymer chain or multiple mechanophore molecules being connected through long alkyl linkages in the polymer backbone.\u003csup\u003e23\u003c/sup\u003e Interesting scenarios can emerge when mechanophores are electronically coupled. For example, mechanochemical study of a fused bis-rhodamine structure showed cooperative reactivity.\u003csup\u003e24\u003c/sup\u003e Only the doubly ring-opened product was observed upon sonication, because the electronics of the singly ring-opened structure accelerates the second ring-opening event. In ladderane structures consisting of multiple fused cyclobutane rings, we discovered strong dynamic effects in their mechanochemical unzipping.\u003csup\u003e25\u003c/sup\u003e The first mechanochemical cycloreversion event accelerates the rate of subsequent cycloreversion, leading to \u0026lsquo;all-or-none\u0026rsquo; unzipping of a ladderane. \u003cem\u003eGem\u003c/em\u003e-difluorocyclopropane has been found to undergo reversible mechanochemical ring-opening to generate a biradical intermediate, which quickly recombines to regenerate \u003cem\u003egem\u003c/em\u003e-difluorocyclopropane upon removal of force.\u003csup\u003e9\u003c/sup\u003e However, incidental reactivity has been observed when two difluorocyclopropane units were connected through one ethylene linkage in a polymer chain. The mechanically generated radicals from two adjacent difluorocyclopropane units combined to cleave the polymer chain leaving alkene chain ends.\u003csup\u003e26\u003c/sup\u003e Without electronic coupling or chemical pathways, isolated mechanophores may not be expected for synergistic reactivity even when tethered together.\u003c/p\u003e\n\u003cp\u003eWe have recently developed a family of multicyclic mechanophores that can be directly polymerized via ring-opening metathesis polymerization (ROMP), generating polymechanophores with every mechanophore repeat unit connected via a backbone alkene.\u003csup\u003e20-22, 27\u003c/sup\u003e\u0026nbsp; In our past polymechanophore systems, strained rings, particularly fused cyclobutanes, were leveraged to induce mechanochemical reactivity of the repeat unit. We hypothesized that, in the absence of significant ring strain or other reaction pathways \u003cem\u003ewithin\u003c/em\u003e the same mechanophore unit, the mechanochemically generated radicals, stabilized by backbone alkenyl linkages, may undergo reaction pathways \u003cem\u003eacross\u003c/em\u003e the polymer backbone. Thus, new types of polymechanophore systems may be envisioned where chemical coupling between appropriately connected individual repeat units can allow cascade chemical reactivity across multiple units, but such mechanochemical reactivity may be absent from an isolated individual unit.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eContemplating the above hypothesis, we designed a polymer system with benzobarrelane (or dihydro-benzobarrelene) repeat units connected by backbone alkenes (\u003cstrong\u003eFig. 1\u003c/strong\u003e). The rationale for choosing a benzobarrelane motif as the repeat unit is based on the following considerations. First, the benzobarrelane scaffold is thermally stable with a low ring strain, and it is not intuitively considered as a potential mechanophore. Second, among the three types of C\u0026ndash;C bonds in the polymer backbone, the C(sp\u003csup\u003e3\u003c/sup\u003e)\u0026ndash;C(sp\u003csup\u003e3\u003c/sup\u003e) bond of benzobarrelane repeat unit is deemed the weakest compared to the other two types of bonds, which are C(sp\u003csup\u003e2\u003c/sup\u003e)=C(sp\u003csup\u003e2\u003c/sup\u003e) and C(sp\u003csup\u003e2\u003c/sup\u003e)\u0026ndash;C(sp\u003csup\u003e3\u003c/sup\u003e) bonds, and thus may be preferentially cleaved. Third, the benzene moieties in benzobarrelane are periplanar with the benzylic C\u0026ndash;H bonds, thus cannot provide stabilization of benzylic radicals. Therefore, the mechanochemically generated biradicals would preferably migrate along the backbone rather than undergo a shift down to the benzobarrelane bridgehead positions.\u0026nbsp;\u003c/p\u003e"},{"header":"Results and Discussion","content":"\u003cp\u003eWe envisioned that the desired poly(alkenyl benzobarrelane) can be accessed via ROMP of a cyclobutene-fused benzobarrelane \u003cstrong\u003e1\u003c/strong\u003e. We synthesized \u003cstrong\u003e1\u003c/strong\u003e from Diels-Alder reaction between anthracene and maleic anhydride followed by a sequence of high yielding reactions that we have previously used to install fused cyclobutene rings (\u003cstrong\u003eFig. 2\u003c/strong\u003e).\u003csup\u003e20\u003c/sup\u003e Attempted ROMP of \u003cstrong\u003e1\u003c/strong\u003e in toluene at room temperature resulted in no conversion, presumably due to the steric hindrance around the cyclobutene. Elevating the temperature to 60 \u0026deg;C gave complete conversion after 20 h, reaching\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003edegrees of polymerization (DP) of 1000. Size exclusion chromatography (SEC) with multiangle light scattering (MALS) analysis of resulting \u003cstrong\u003epoly1\u0026nbsp;\u003c/strong\u003erevealed very low dispersity \u0026lt;1.05 and measured \u003cem\u003eM\u003c/em\u003e\u003csub\u003en\u003c/sub\u003e = 226 kDa in excellent agreement with the theoretical molecular weight (MW), even with the slow-initiating Grubbs II catalyst. The good control of MW distribution in ROMP of \u003cstrong\u003e1\u003c/strong\u003e using a slow initiator suggested slow propagation of \u003cstrong\u003e1\u003c/strong\u003e and negligible chain transfer in \u003cstrong\u003epoly1\u003c/strong\u003e. In our previous designs of polymechanophores, at least one strained cyclobutane is present in the repeat unit along the backbone.\u003csup\u003e20-22, 27-28\u003c/sup\u003e The strain release upon cycloreversion of cyclobutane provides the driving force for efficient mechanoactivation. In contrast to cyclobutane, benzobarrelane has a low ring strain energy of 9.7 kcal/mol (\u003cstrong\u003eSI S6.4\u003c/strong\u003e), and therefore we were curious about its mechanochemical reactivity.\u003c/p\u003e\n\u003cp\u003eWe subjected \u003cstrong\u003epoly1\u003c/strong\u003e with DP = 1000 at a concentration of 1 mg/mL in THF to sonication using a typical sonochemical protocol.\u003csup\u003e29\u003c/sup\u003e SEC analysis of the sonicated polymer at different time points showed that the original polymer peak significantly decreased within 1 h and disappeared in 2 h, accompanying the appearance of a broader, lower MW peak (\u003cstrong\u003eFig. 3b\u003c/strong\u003e). This evolution of SEC profile is commonly observed from sonochemical mechanoactivation of narrow-disperse polymers, due to nonselective main chain cleavage.\u003csup\u003e8, 22, 29\u003c/sup\u003e\u0026nbsp; \u003csup\u003e1\u003c/sup\u003eH NMR analysis of the sonicated \u003cstrong\u003epoly1\u003c/strong\u003e showed the emergence of multiple new broad signals between 7 and 4.5 ppm. The new signals in 7.5-6.5 and 5.5-4.5 ppm regions overlapped with the backbone alkene and aromatic signals of pristine \u003cstrong\u003epoly1\u003c/strong\u003e (\u003cstrong\u003eFig. 3d\u003c/strong\u003e). After subtracting the signals of pristine \u003cstrong\u003epoly1\u003c/strong\u003e,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ethe integration of the newly generated signals in the regions of 7.5-6.5, 6.5-5.5, and 5.5-4.5 ppm gave a 1:1:1 ratio, and their intensity corresponded to the decrease in intensity of the original \u003cstrong\u003epoly1\u0026nbsp;\u003c/strong\u003esignals. We hypothesized that the\u0026nbsp;backbone alkenes allow resonance of allylic biradicals generated upon the mechanochemical cleavage of the backbone C(sp\u003csup\u003e3\u003c/sup\u003e)\u0026ndash;C(sp\u003csup\u003e3\u003c/sup\u003e) bond in a benzobarrelane unit. This resonance facilitates fragmentation of the backbone C(sp\u003csup\u003e3\u003c/sup\u003e)\u0026ndash;C(sp\u003csup\u003e3\u003c/sup\u003e) bond in the immediately adjacent benzobarrelane units, thus providing a mechanism for radical propagation along the polymer backbone to neighboring units. As such, the repeat unit of the transformed polymer would consist of a dihydroanthracene resulting from the ring-opening of benzobarrelane and a conjugated diene (\u003cstrong\u003eFig. 3a\u003c/strong\u003e). We suspected the newly formed diene to be susceptible to cross metathesis, while the backbone alkenes in original \u003cstrong\u003epoly1\u0026nbsp;\u003c/strong\u003eare inert to cross metathesis due to steric hindrance as indicated by the very low dispersity of \u003cstrong\u003epoly1\u003c/strong\u003e.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThus,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ewe subjected \u003cstrong\u003epoly1\u003c/strong\u003e and\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003esonicated \u003cstrong\u003epoly1\u0026nbsp;\u003c/strong\u003eto excess \u003cem\u003eZ\u003c/em\u003e-hex-3-ene and Hoveyda-Grubbs II catalyst at 60 \u0026deg;C. Indeed, the SEC trace of \u003cstrong\u003epoly1\u0026nbsp;\u003c/strong\u003eremained unchanged, but that of the sonicated \u003cstrong\u003epoly1\u003c/strong\u003e shifted to lower MW (\u003cstrong\u003eFig. 3c\u003c/strong\u003e). For sonicated \u003cstrong\u003epoly1\u003c/strong\u003e, the high MW peak corresponding to uncleaved polymer significantly decreased its intensity after cross metathesis, suggesting that mechanoactivation occurred in polymer strands that did not undergo chain cleavage.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo assign the NMR signals of mechanochemically transformed polymer, we sought to synthesize a model compound representing its expected constituent structure,\u003cem\u003e\u0026nbsp;syn\u003c/em\u003e-dibutadienyl-dihydroanthracene, which is not reported in literature. In our initial attempts, we synthesized \u003cem\u003esyn\u003c/em\u003e-di(bromovinyl)-dihydroanthracene, which was subjected to various cross coupling conditions to generate the desired dibutadienyl substitution, but led to complex inseparable mixtures (\u003cstrong\u003eScheme S1\u003c/strong\u003e). We speculated that the acidic protons in dihydroanthracene interfered with the cross coupling reaction. We then sought to replace the problematic acidic protons in dihydroanthracene with methyl substituents. Indeed, the dimethyl derivative underwent smooth Stille coupling with a vinyl tin species to give\u003cem\u003e\u0026nbsp;syn\u003c/em\u003e-9,10-dimethyl-9,10-dienyl-9,10-dihydroanthracene (\u003cstrong\u003eScheme S2\u003c/strong\u003e). We synthesized this reference structure with \u003cem\u003eZ\u003c/em\u003e, \u003cem\u003eE\u003c/em\u003e or \u003cem\u003eE\u003c/em\u003e, \u003cem\u003eE\u003c/em\u003e configurations for the dienyl substituents. NMR spectra of these compounds showed alkenyl signals from the dienes in the range of 5.5-6.0 ppm for \u003cem\u003eZ\u003c/em\u003e, \u003cem\u003eE\u003c/em\u003e and 5.7-6.5 ppm for \u003cem\u003eE\u003c/em\u003e, \u003cem\u003eE\u003c/em\u003e isomer (see \u003cstrong\u003eSI S2.2\u003c/strong\u003e), thus allowing us to assign the emergent signals in sonicated \u003cstrong\u003epoly1\u0026nbsp;\u003c/strong\u003ein 5.5-6.5 ppm and 6.5-7 ppm regions to the mechanochemically generated backbone dienes. The benzylic protons in dihydroanthracene were assigned to the signals in the 4.5-5.5 ppm region based on literature examples.\u003csup\u003e30\u003c/sup\u003e Due to the overlapping \u003csup\u003e1\u003c/sup\u003eH NMR signals of pristine and mechanoactivated \u003cstrong\u003epoly1\u003c/strong\u003e, we subtracted the alkene signals from the unreacted \u003cstrong\u003epoly1\u003c/strong\u003e to use the newly generated diene signals to calculate the percentage of mechanoactivation (see \u003cstrong\u003eSI S4\u003c/strong\u003e)\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003efor details of the analysis). As such, we quantified that 36% of the benzobarrelane repeat units were converted to dialkenyl dihydro-anthracene in 150 min of sonication (\u003cstrong\u003eFig. 3d\u003c/strong\u003e). This extent of mechanoactivation is indeed similar to what we have observed in our previous polymechanophore systems containing strained cyclobutane repeat units at the same duration of sonication.\u003csup\u003e21-22\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe next probed the structural features necessary for the observed mechanochemical transformation using control polymers (\u003cstrong\u003eFig. 4\u003c/strong\u003e). Based on our postulated radical cascade mechanism, backbone alkene linkages connecting the benzobarrelane repeat units are required to migrate the radicals to the neighboring units. Hydrogenating the backbone alkenes\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eshould thus prevent this pathway. Indeed, the hydrogenated \u003cstrong\u003epoly1\u003c/strong\u003e showed no discernable change in its NMR spectrum upon prolonged sonication (\u003cstrong\u003eFig. S2\u003c/strong\u003e). Alkenyl substituents are known to lower the threshold force for mechanochemical ring-opening of cyclobutene compared to alkyl substituents, due to the stabilization of the biradical intermediate upon C\u0026ndash;C bond cleavage.\u003csup\u003e31\u003c/sup\u003e To ensure that the absence of structural changes is not due to increased threshold force for mechanoactivation, we designed another control polymer, where the dialkenyl backbone linkage to benzobarrelane is preserved but the neighboring benzobarrelane units are distanced by an alkyl spacer. We found that \u003cstrong\u003e1\u003c/strong\u003e and 2,3-dihydrofuran (DHF), a comonomer that we previously reported to greatly suppress homoaddition of norbornenes,\u003csup\u003e32\u003c/sup\u003e can undergo truly random copolymerization at 40 \u0026deg;C in toluene. The \u003csup\u003e1\u003c/sup\u003eH NMR spectrum of the isolated polymer revealed equal composition of \u003cstrong\u003e1\u003c/strong\u003e and DHF, and its \u003csup\u003e1\u003c/sup\u003eH and \u003csup\u003e13\u003c/sup\u003eC NMR spectra showed no signals corresponding to the homodyads of \u003cstrong\u003e1\u003c/strong\u003e or DHF (\u003cstrong\u003eFig. S3\u003c/strong\u003e). SEC-MALS analysis showed \u003cem\u003eM\u003c/em\u003e\u003csub\u003en\u003c/sub\u003e = 148 kDa, corresponding to ~500 units of ring-opened \u003cstrong\u003e1\u003c/strong\u003e and DHF combined. Computed contour lengths of a ring-opened \u003cstrong\u003e1\u003c/strong\u003e-DHF hetero-dyad and a homo-dyad of \u003cstrong\u003e1\u003c/strong\u003e are 8.5 and 6.4 \u0026Aring;, respectively (\u003cstrong\u003eFig. S19\u003c/strong\u003e), thus the synthesized \u003cstrong\u003epoly(1-\u003cem\u003eco\u003c/em\u003e-DHF)\u0026nbsp;\u003c/strong\u003ehad a greater contour length than the studied \u003cstrong\u003epoly1\u003c/strong\u003e, and would be expected to experience sufficiently high forces during sonication as for \u003cstrong\u003epoly1\u003c/strong\u003e. Nevertheless, sonication of \u003cstrong\u003epoly(1-\u003cem\u003eco\u003c/em\u003e-DHF)\u0026nbsp;\u003c/strong\u003eunder the same conditions as for \u003cstrong\u003epoly1\u0026nbsp;\u003c/strong\u003edid not yield any new detectable NMR signals. We wondered if biradical species might be generated transiently from the benzobarrelane structure in \u003cstrong\u003epoly(1-\u003cem\u003eco\u003c/em\u003e-DHF)\u003c/strong\u003e, so we attempted sonication in the presence of potent radical trapping or hydrogen transfer agents. However, even sonicating \u003cstrong\u003epoly(1-\u003cem\u003eco\u003c/em\u003e-DHF)\u0026nbsp;\u003c/strong\u003ein the presence of\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ea large excess of 1,4-cyclohexadiene or tetracyanoethylene, gave no change in \u003csup\u003e1\u003c/sup\u003eH NMR signals (\u003cstrong\u003eFig. S4\u003c/strong\u003e).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eWe rationalized that even though \u003cstrong\u003epoly(1-\u003cem\u003eco\u003c/em\u003e-DHF)\u0026nbsp;\u003c/strong\u003emight give rise to ring-opening of a benzobarrelane unit, the transiently generated biradical species cannot effectively migrate in the absence of a chemically coupled neighboring benzobarrelane unit. Thus, any mechanochemically generated biradicals within a benzobarrelane unit would spontaneously recombine upon removal of force.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;We used calculation to further understand the mechanism of this polymeric mechanochemical transformation. We first used \u003cem\u003eab initio\u003c/em\u003e steered molecular dynamics (AISMD)\u003csup\u003e33\u003c/sup\u003e to simulate the dynamics of mechanoactivation of a computationally manageable tetramer system (\u003cstrong\u003eFig. 5a\u003c/strong\u003e), using the unrestricted B3LYP density functional on a 6-31G* basis set with Grimme\u0026rsquo;s third generation empirical dispersion\u003csup\u003e34\u003c/sup\u003e (at UB3LYP-D3/6-31G* level of theory). 30 AISMD simulations were performed under an external pulling force \u003cem\u003ef\u003c/em\u003e = 2.5 nN for a total run time of 5 ps in each simulation (\u003cstrong\u003eSI S6.2\u003c/strong\u003e for details). The AISMD simulations showed that the radical cascade can be initiated by bond cleavage from any benzobarrelane unit, but more often from an internal unit. The cascade ring-opening can be represented by plotting scissile bond length over simulation time (\u003cstrong\u003eFig. 5b\u003c/strong\u003e). In an exemplary simulation, the first bond cleavage occurs at the C\u003csub\u003e3\u003c/sub\u003e\u0026ndash;C\u003csub\u003e4\u003c/sub\u003e bond (atomic indices in \u003cstrong\u003eFig. 5a\u003c/strong\u003e), followed by cleavage of C\u003csub\u003e5\u003c/sub\u003e\u0026ndash;C\u003csub\u003e6\u003c/sub\u003e, C\u003csub\u003e7\u003c/sub\u003e\u0026ndash;C\u003csub\u003e8\u003c/sub\u003e, and lastly C\u003csub\u003e1\u003c/sub\u003e\u0026ndash;C\u003csub\u003e2\u003c/sub\u003e bond (\u003cstrong\u003eFig. 5b\u003c/strong\u003e). Upon mechanoactivation, the first C\u0026ndash;C bond cleavage forms biradicals, which subsequently fragment the C\u0026ndash;C bond of the adjacent benzobarrelane unit, leading to the formation of a conjugated diene between ring-opened repeat units. The biradical cascade can be analyzed using Mulliken atomic spin density\u003csup\u003e35\u003c/sup\u003e values during the AISMD simulation to visualize radical migration along the backbone bonds. In \u003cstrong\u003eFig. 5c\u003c/strong\u003e,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eupon the C\u003csub\u003e3\u003c/sub\u003e\u0026ndash;C\u003csub\u003e4\u003c/sub\u003e bond cleavage, biradicals are formed at C\u003csub\u003e3\u003c/sub\u003e and C\u003csub\u003e4\u003c/sub\u003e positions as their spin density values quickly spiked to +1 and \u0026ndash;1. Immediately after the bond cleavage, the biradicals on C\u003csub\u003e3\u003c/sub\u003e and C\u003csub\u003e4\u003c/sub\u003e delocalize within bridging conjugated dienes B\u003csub\u003e23\u003c/sub\u003e and B\u003csub\u003e45\u003c/sub\u003e, respectively. Subsequently, the biradicals start to migrate in opposite directions along the backbone. The free radical on B\u003csub\u003e45\u003c/sub\u003e traverses through the unit of B\u003csub\u003e67\u003c/sub\u003e, and then locates on the end diene E\u003csub\u003e8\u003c/sub\u003e, while the other radical on B\u003csub\u003e23\u003c/sub\u003e traverses to the other end diene E\u003csub\u003e1\u003c/sub\u003e. After about 3 ps simulation, the spin densities are distributed only at the two ends of the fully ring-opened tetramer, with no spin densities found in the formed internal dienes connecting the ring-opened benzobarrelane units. All the AISMD simulations showed that after the first bond is mechanochemically cleaved in the tetramer, the generated biradicals migrate along the backbone bonds connecting the benzobarrelane units, and eventually locate at the end of the ring-opened product. Furthermore, the simulation indicated a strong preference for sequential mechanoactivation. Out of a total of 30 simulations, 26 showed that upon ring-opening of one benzobarrelane unit, its immediately connected or neighboring unit is activated next. Only 4 out of 30 simulations showed that the subsequent mechanoactivation is from a non-neighboring unit after the first mechanoactivation (\u003cstrong\u003eTable S3 and Fig. S6\u003c/strong\u003e). This observation suggested a sequential cascade and cooperative mechanoactivation behavior for the investigated polymer system.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Additionally, we investigated the electronic structures and kinetics of the radical cascade reaction under applied forces by calculating the force-modified potential energy surface (FMPES).\u003csup\u003e33\u003c/sup\u003e We focused on the mechanoactivation of dimeric structure \u003cstrong\u003e2\u003c/strong\u003e, which is the minimum necessary structure for probing the mechanism and the formation of biradical intermediate \u003cstrong\u003e3\u003c/strong\u003e and mechanochemical product \u003cstrong\u003e4\u003c/strong\u003e (\u003cstrong\u003eFig. 6a\u003c/strong\u003e). We calculated FMPES at force levels from 0.5 to 2.5 nN using the same UB3LYP-D3/6-31G* level of theory (\u003cstrong\u003eSI S6.3\u0026nbsp;\u003c/strong\u003efor details). Two critical reaction steps were found during the minimum energy path (MEP) optimization on the FMPES: the first bond cleavage in \u003cstrong\u003e2\u003c/strong\u003e to form biradical intermediate \u003cstrong\u003e3\u003c/strong\u003e, and the second bond cleavage of the neighboring unit in \u003cstrong\u003e3\u003c/strong\u003e to form product \u003cstrong\u003e4\u003c/strong\u003e with a diene\u003cem\u003e\u0026nbsp;\u003c/em\u003elinkage. For both reaction steps, as the external force is increased, the activation energies are lowered with the transition state occurring earlier towards the reactant (\u003cstrong\u003eFig. 6b\u003c/strong\u003e). Furthermore, under the same external force, barrier heights of the two reaction steps were found to be similar, which could imply similar rates of C\u0026ndash;C bond cleavage. Electron density distribution on the molecular orbitals (SOMO\u003csub\u003e1\u003c/sub\u003e and SOMO\u003csub\u003e2\u003c/sub\u003e) of the critical geometries also supported the mechanism of radical cascade mechanoactivation (\u003cstrong\u003eFig. 6c\u003c/strong\u003e). The transition state of the first ring-opening reaction \u003cstrong\u003eTS\u003csub\u003e2-3\u003c/sub\u003e\u003c/strong\u003e\u003csub\u003e\u0026nbsp;\u003c/sub\u003einvolves\u0026nbsp;\u003cem\u003es\u003c/em\u003e-bond cleavage that creates the biradical intermediate \u003cstrong\u003e3\u003c/strong\u003e. In the second ring-opening transition state structure \u003cstrong\u003eTS\u003csub\u003e3-4\u003c/sub\u003e\u003c/strong\u003e, the biradicals migrate\u0026nbsp;in opposite directions through\u0026nbsp;p-orbitals. In product \u003cstrong\u003e4\u003c/strong\u003e,\u0026nbsp;the electrons are localized at the two terminal dienes (\u003cstrong\u003eFig. 6c\u003c/strong\u003e). Beyond the presented MEPs under forces, microkinetic modeling was performed considering all critical geometries, transition states, and rate constants for all possible reaction steps in this dimeric system (\u003cstrong\u003eFig. S11\u003c/strong\u003e). The results showed that as the external force is raised by each 0.5 nN increment, the time scale for ring-opening lowers dramatically by four to five orders of magnitude (\u003cstrong\u003eFig. S12\u003c/strong\u003e). Furthermore, as the force is increased, intermediate \u003cstrong\u003e3\u003c/strong\u003e is significantly stabilized with a much longer lifetime (\u003cstrong\u003eFig. S12\u003c/strong\u003e). Under experimental conditions, the biradical product \u003cstrong\u003e4\u003c/strong\u003e is likely susceptible to hydrogen abstraction in solution to become closed-shell species.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe have designed a polymechanophore system with benzobarrelane repeat units connected by backbone alkenes via living polymerization of a cyclobutene-fused benzobarrelane. Upon sonication, polybenzobarrelane was transformed into dihydroanthracene repeat units connected by dienes via a radical cascade mechanism. Despite the assumed low mechanochemical reactivity of benzobarrelane, the achievable degrees of mechanoactivation are similar to those in our previously reported polymechanophore systems consisting of highly strained structures in repeat units. Uniquely, isolated benzobarrelane that is not connected with another benzobarrelane via an alkene linkage did not give any detectable products under the same sonication conditions. \u003cem\u003eAb initio\u003c/em\u003e steered molecular dynamics and electronic structure calculations of the mechanoactivation of this polymechanophore system supported the radical cascade mechanism, where mechanochemically generated radicals from ring-opening of one benzobarrelane unit propagate along the polymer backbone to ring open neighboring units. The described system is unique in that its mechanochemical reactivity is observed only when neighboring repeat units are coupled through a viable path for cascade radical reactions, but is absent from isolated individual units. New opportunities in polymer mechanochemistry emerge as we shift the focus from considering the reactivity of individual molecular structures to designing polymeric scaffolds that exhibit mechanically induced cascade reactivities to rearrange polymer backbones. More broadly, novel reactivities of polymeric scaffolds may be elicited by enabling chemical coupling or collective interactions of otherwise inert individual molecules. We envision the possibility of mechanically initiating reactions that can propagate along the polymer chain, leading to amplified mechanochemical response of macromolecular systems.\u0026nbsp;\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cu\u003eAuthor Contribution\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e‡\u003c/sup\u003eThese authors contributed equally to this work.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAcknowledgement\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the U.S. Army Research Office under grant number W911NF2420055 and the National Science Foundation under award number 2350170.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eData Availability\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eExperimental details, additional experiments and characterizations, NMR spectra, and computational details are available in supplementary information.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eCompeting Interests\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing financial interests.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eMaterials, data, and correspondence should be addressed to:\u003c/u\u003e\u003c/p\u003e\n\u003cp\[email protected] (Y.X.); [email protected] (T.M.)\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eStaudinger, H.; Heuer, W., \u0026Uuml;ber hochpolymere Verbindungen, 93. 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Phys. \u003c/em\u003e\u003cstrong\u003e1955,\u003c/strong\u003e \u003cem\u003e23\u003c/em\u003e (10), 1833-1840.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7133429/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7133429/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Mechanical force can trigger non-destructive chemical transformations of force-responsive molecules, mechanophores, that are embedded in a long polymer chain to change or induce a variety of their physical and chemical properties. Studies on polymer mechanochemistry have thus far focused on the design and understanding of the reactivity of individual mechanophores. However, when mechanophores, or even molecular structures that are not typically considered force-responsive, are coupled with each other in the polymer backbone, new reactivity and force response that are absent from discrete molecules may arise to transform polymer backbone structures. Herein, we describe a system where mechanically triggered backbone bond scission generates biradical intermediates, which then undergo radical cascade reactions to transform polymer backbone structure. Our design is based on a polymer with benzobarrelane repeat units that are connected via backbone alkenes. The alkene linkage is crucial for the radical cascade ring-opening reactions to occur across multiple connected benzobarrelane units. In contrast, no mechanochemical reaction was observed in isolated benzobarrelane units that are separated by alkyl linkages, even when the alkenyl substituents of benzobarrelane were preserved. Despite the lack of weak covalent bonds or significant ring strain in the benzobarrelane polymer, it achieved similar degrees of mechanochemical transformation as our previously reported polyladderene systems consisting of repeat units of highly strained fused cyclobutanes. Ab initio steered molecular dynamics and force-modified potential energy surface calculations supported the force-induced radical cascade mechanism along the polymer backbone. Simulations indicated a strong preference for sequential mechanoactivation: upon ring-opening of one benzobarrelane unit, its immediately neighboring unit is most likely to be activated next. This work demonstrates a new strategy for designing mechanically responsive polymers by creating chemical pathways to promote cooperative mechanoactivation across neighboring units. It further underscores the potential to elicit novel reactivities through the collective interaction of otherwise inert individual molecules.","manuscriptTitle":"Cascade Mechanochemical Transformation of a Benzobarrelane Polymer: A Neighboring Repeat Unit Effect","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-22 12:49:46","doi":"10.21203/rs.3.rs-7133429/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1fa69551-59aa-45b8-8a9e-0ca925d3e9ac","owner":[],"postedDate":"July 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":51624503,"name":"Physical sciences/Chemistry/Polymer chemistry/Polymer synthesis"},{"id":51624504,"name":"Physical sciences/Chemistry/Organic chemistry/Reaction mechanisms"},{"id":51624505,"name":"Physical sciences/Chemistry/Theoretical chemistry/Reaction mechanisms"}],"tags":[],"updatedAt":"2025-08-14T11:16:01+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-22 12:49:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7133429","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7133429","identity":"rs-7133429","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}