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Tetrafunctional cyclobutanes tune toughness via network strand continuity

Nature Chemistry (2025)Cite this article

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Abstract

Customizing the toughness of polymer networks independently of their chemical composition and topology remains an unsolved challenge. Traditionally, polymer network toughening is achieved by using specialized monomers or solvents or adding secondary networks/fillers that substantially alter the composition and may limit applications. Here we report a class of force-responsive molecules—tetrafunctional cyclobutanes (TCBs)—that enable the synthesis of single-network end-linked gels with substantially decreased or increased toughness, including unusually high toughness for dilute end-linked gels, with no other changes to network composition. This behaviour arises from stress-selective force-coupled TCB reactivity when stress is imparted from multiple directions simultaneously, which traditional bifunctional mechanophores cannot access. This molecular-scale mechanoreactivity translates to bulk toughness through a topological descriptor, network strand continuity, that describes the effect of TCB reactivity on the consequent local network topology. TCB mechanophores and the corresponding concepts of stress-selective force-coupled reactivity and strand continuity offer design principles for tuning the toughness of simple yet commonly used single-network gels.

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Fig. 1: Design of end-linked networks with TCB junctions.
Fig. 2: Computational investigation of lowest-energy force-coupled CB reaction barriers under various stress orientations.
Fig. 3: Mechanical properties of TCB versus Control gels.
Fig. 4: Effects of junction cleavage regioselectivity on fracture behaviour.

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Data availability

All data are available in the main text, in the Supplementary Information or via Figshare at https://doi.org/10.6084/m9.figshare.29973850 (ref. 71). Crystallographic data for the structure reported in this Article have been deposited at the Cambridge Crystallographic Data Centre, under deposition number CCDC 2448803 (CB-C2). Copies of the data can be obtained free of charge at https://www.ccdc.cam.ac.uk/structures.

Code availability

The computational codes for this work are available via Github at https://github.com/olsenlabmit/Cyclobutane-junctions-network-toughnening.

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Acknowledgements

The authors acknowledge the MIT SuperCloud and Lincoln Laboratory Supercomputing Center for providing HPC resources that have contributed to the research results reported within this paper. This work was supported by the NSF Center for the Chemistry of Molecularly Optimized Networks (MONET), CHE-2116298. A.H.-A. acknowledges the MIT Martin Family Fellowship for funding. The authors gratefully acknowledge M. Kim and X. Zheng for integrating BigSMILES notation for the polymers within this work. Funding for this study was provided by the NSF Center for the Chemistry of Molecularly Optimized Networks (MONET), CHE-2116298 and the MIT Martin Family Society of Fellows for Sustainability (A.H.-A.).

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Authors and Affiliations

  1. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA

    Abraham Herzog-Arbeitman, Julianna Lian, Peter Mueller, Heather J. Kulik & Jeremiah A. Johnson

  2. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Ilia Kevlishvili, Devosmita Sen, Joshika Chakraverty, Bradley D. Olsen & Heather J. Kulik

  3. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Shu Wang

  4. Department of Chemistry, Duke University, Durham, NC, USA

    Stephen L. Craig

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Contributions

A.H.-A., I.K., B.D.O., J.A.J. and S.L.C. conceptualized the studies. A.H.-A. and J.L. synthesized materials and fabricated testing samples. A.H.-A. and S.W. conducted mechanical testing and other characterizations. EFEI studies were conducted by I.K. and supervised by H.J.K. Network tensile simulation and analysis was done by D.S., J.C. and supervised by B.D.O. Single-crystal X-ray diffraction and analysis was done by P.M. J.A.J., B.D.O., S.L.C. and H.J.K. acquired funding. A.H.-A. and J.A.J. drafted and edited the manuscript; all authors edited and discussed the manuscript.

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Correspondence to Bradley D. Olsen, Heather J. Kulik, Stephen L. Craig or Jeremiah A. Johnson.

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Competing interests

The authors declare the following competing interests: J.A.J., S.W. and A.H.A. are inventors listed on a patent, International Application Number PCT/US2024/033425, owned by MIT and Duke University, which describes the synthesis and use of the junctions described above and other related molecules. All other authors declare no competing interests.

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Extended data

Extended Data Fig. 1 Control junction, and construction of a control end-linked network, Control-G.

For Detailed conditions, see Methods. PC: propylene carbonate.

Extended Data Fig. 2 Simulated CB-C2, CB-C1, and CB-ether model junction mechanochemical reaction barriers.

Top: simulated barriers to cycloelimination and C–O heterolysis under external force. Right, Inset: CB-ether junction structure as synthesized. Bottom: mechanochemical reactions simulated. The simulated transition state for C–O heterolysis for CB-C1 under cis-1,2-stress is shown, illustrating the intact cyclobutane ring even under the most favourable stress-orientation for [2 + 2]cycloelimination.

Extended Data Fig. 3 Bulk characterization of TCB and Control gels.

Top left: FTIR spectra for gels, as prepared. Top right, Young’s moduli for all unnotched pure shear samples for each junction composition. Error bars show ±1 standard deviation, for n = 3 samples from a single gel sheet each. Bottom: representative rheology characterization (amplitude sweep, left; frequency sweep, right) for each gel composition.

Extended Data Fig. 4 Full stress–strain curves for determination of tearing energy in PC gels.

Notched and unnotched samples for all tested network chemistries. Unnotched samples are shaded darker.

Extended Data Fig. 5 Modulus, tearing energy, and full stress–strain curves for determination of tearing energy in MeOPh gels.

a) Frequency sweeps on as-synthesized MeOPh gels. b) Young’s modulus derived from tearing energy samples. Error bars show ±1 standard deviation, for n = 3 samples from a single gel sheet each. c) Full stress–strain curves for notched and unnotched samples of MeOPh gels. Replicates of unnotched samples were not shown for clarity. d) Tearing energy vs. critical stress values for the stress–strain curves in (c). Box-and-whisker plots, inset, show tearing energy measurements, with white lines indicating the median value and black lines showing the mean. Box edges show first and third quartile; whiskers denote data range. Each tearing energy value is derived samples (n = 4 for CB-C1 and Control; n = 3 for CB-C2) and cut from a single gel sheet to remove batch-to-batch variation.

Extended Data Fig. 6 EFEI calculated barriers for model junctions in aqueous contexts.

a) Barriers for all pathways in CB-C1 models. b) Barriers for relevant pathways in CB-C2 models. The cis 1,2 orientation has the lowest barrier to [2 + 2] cycloelimination, and the 1,3 orientation has the lowest barrier to C–O heterolysis, thus behaviour is qualitatively similar to PC gels. c) Barriers for all pathways in CB-C1 models. d) Barrier to C–C homolysis in the control model. In a)–c), darker lines denote [2 + 2] cycloelimination pathways; lighter lines denote C–O heterolysis.

Extended Data Fig. 7 Fluorescence microscopy imaging and quantification of damaged gels.

a, d, g, j), Overlayed brightfield and fluorescence images of twisted regions of gels after dyeing. An example gel after twisting is shown in Supplementary Fig. S3. b, e, h, k) Fluorescence images without brightfield images overlayed. Bright line patterns in (b) and (e) show CB-C2 activation in areas of damage. These patterns are faint in CB-C1 where ring-opening is discouraged and nonexistent in Control networks. c, f, i, l) Fluorescence intensity (quantified by mean grey value) along the dashed arrows shown in (a, d, g, j), respectively. Shaded regions in (c, f, I,l) indicate average background fluorescence ±1 standard deviation, measured on undamaged ends of the same samples, see Supplementary Fig. S3. (a–f) display CB-C2 fluorescence, (g–i) CB-C1, and (j–l) correspond to Control. Lines of high fluorescence only occur in regions buckled during twisting, and follow the warped curvature of the sample, for example the gel edge at the top of (a) and (b), consistent with CB-C2 activation as stress concentrates near geometric distortions. Razor-cut gel edges showed high but variable fluorescence. m) Reaction schematic for attachment of TAMRA to the olefin residues of activated TCBs. Mean grey values shown correspond to fluorescence intensity only. All images were captured using the same laser gain and exposure time for straightforward comparison.

Extended Data Fig. 8 Fluorescence microscopy imaging of hammered CB-C2-G.

Upper: brightfield and fluorescence images overlayed. Lower: fluorescence image. Laser settings were altered from images in Extended Data Fig. 7 to improve contrast and detail visibility.

Extended Data Fig. 9 Toughness measurements including CB-ether.

Measured tearing energies vs. critical stress (top) and toughnesses (work of fracture) vs. strain-at-break (bottom) for all tested networks including CB-ether. Other networks tested are shown for comparison. CB-ether-G tearing energy is statistically greater than Control-G networks (1-tailed t-test, \(p=0.002\)), but not from CB-C2-G (\(p=0.62\)). CB-ether-G toughness is statistically greater than Control-G and CB-C1-G networks (1-tailed t-test, \(p=0.015,p=0.024\), respectively). Box plots are shown with white lines indicating the median value and black lines showing the mean. Box edges show first and third quartile; whiskers denote data range. Each tearing energy value is derived from samples (n = 6 for CB-C1, CB-C2 and CB-ether; n = 7 for Control) cut from a single gel sheet. Toughness values are derived from n = 4 (2); 6(3); 9(4); 7(4) total replicates (number of biological replicates in parentheses), from left to right.

Extended Data Fig. 10 Comparison of toughness, stiffness, and orthogonality of the two in dilute single-network gels.

a) End-linked PEG networks of varying cross-link density, including TetraPEG (A4 + B4) other A2 + B4 networks (like this work) and other mechanophore networks (Wang et al.19). TCB gels are marked by stars. b) Pendant-linked single-network gels of varied chemistry and topology, including polysaccharide, poly(vinyl alcohol) (PVA), polyacrylamide (PAam), and slide-ring gels, compared to this work. Details for shown data can be found in Supplementary Table 6. Gels in (a) and (b) are \(88\pm 4 \%\) solvent by weight, are made up of only a single network, and do not involve multistep fabrication or fillers. We note that highly entangled PAam gels11 do fit these criteria and achieve high stiffness and toughness; these materials have been omitted simply to improve readability of the other data. Highly entangled PAam gels within this concentration range can achieve tearing energies between 73 J/m2 and 1.5 kJ/m2, alongside Young’s moduli of 190 kPa to 100 kPa, respectively, depending on water content during gelation. c) Tearing energy vs. modulus for several material families normalized by the tearing energy and modulus of the toughest sample of each dataset, illustrating differing correlations between these properties.

Supplementary information

Supplementary Information Materials and Methods

Supplementary Text, Figs. 1–14, Tables 1–8 and References.

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Herzog-Arbeitman, A., Kevlishvili, I., Sen, D. et al. Tetrafunctional cyclobutanes tune toughness via network strand continuity. Nat. Chem. (2025). https://doi.org/10.1038/s41557-025-01984-9

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