Light-driven molecular trap enables bidirectional manipulation of dynamic covalent systems


Bond formation between two molecular entities in a closed system strictly obeys the principle of microscopic reversibility and occurs in favour of the thermodynamically more stable product. Here, we demonstrate how light can bypass this fundamental limitation by driving and controlling the reversible bimolecular reaction between an N-nucleophile and a photoswitchable carbonyl electrophile. Light-driven tautomerization cycles reverse the reactivity of the C=O/C=N-electrophiles (‘umpolung’) to activate substrates and remove products, respectively, solely depending on the illumination wavelength. By applying either red or blue light, selective and nearly quantitative intermolecular bond formation/scission can be achieved, even if the underlying condensation/hydrolysis equilibrium is thermodynamically disfavoured. Exploiting light-driven in situ C=N exchange, our approach can be used to externally regulate a closed dynamic covalent system by actively and reversibly removing specific components, resembling a molecular and bidirectional version of a macroscopic Dean–Stark trap.

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Fig. 1: Concept of driving thermally reversible covalent bond formation/scission with light.
Fig. 2: Light-driven bond formation/cleavage cycle.
Fig. 3: UV–vis absorption spectra.
Fig. 4: Light-driven C–N bond formation/scission for an amine nucleophile.
Fig. 5: Light-driven C–N bond formation/scission for a hydrazide nucleophile.
Fig. 6: Light-driven compositional shifting of a coupled thermodynamic equilibrium.


  1. 1.

    Astumian, R. D. Microscopic reversibility as the organizing principle of molecular machines. Nat. Nanotech. 7, 684–688 (2012).

    CAS  Article  Google Scholar 

  2. 2.

    Boltzmann, L. Über die Beziehung zwischen dem zweiten Hauptsatz der mechanischen Wärmetheorie und der Wahrscheinlichkeitsrechnung respektive den Sätzen über das Wärmegleichgewicht. Wien. Ber. 76, 373–435 (1877).

    Google Scholar 

  3. 3.

    Qian, H. Phosphorylation energy hypothesis: open chemical systems and their biological functions. Annu. Rev. Phys. Chem. 58, 113–142 (2007).

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Schultz, D. M. & Yoon, T. P. Solar synthesis: prospects in visible light photocatalysis. Science 343, 1239176 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Shaw, M. H., Twilton, J. & MacMillan, D. W. C. Photoredox catalysis in organic chemistry. J. Org. Chem. 81, 6898–6926 (2016).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Feringa, B. L & Browne, W. R. Molecular Switches (Wiley-VCH, Weinheim, 2011).

  7. 7.

    Bandara, H. M. D. & Burdette, S. C. Photoisomerization in different classes of azobenzene. Chem. Soc. Rev. 41, 1809–1825 (2012).

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Klajn, R. Spiropyran-based dynamic materials. Chem. Soc. Rev. 43, 148–184 (2014).

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Irie, M., Fukaminato, T., Matsuda, K. & Kobatake, S. Photochromism of diarylethene molecules and crystals. Chem. Rev. 114, 12174–12277 (2014).

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Kathan, M. & Hecht, S. Photoswitchable molecules as key ingredients to drive systems away from global thermodynamic minimum. Chem. Soc. Rev. 46, 5536–5550 (2017).

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Lemieux, V., Gauthier, S. & Branda, N. R. Selective and sequential photorelease using molecular switches. Angew. Chem. Int. Ed. 45, 6820–6824 (2006).

    CAS  Article  Google Scholar 

  12. 12.

    Samachetty, H. D. & Branda, N. R. Integrating molecular switching and chemical reactivity using photoresponsive hexatrienes. Pure Appl. Chem. 78, 2351–2359 (2006).

    CAS  Article  Google Scholar 

  13. 13.

    Sud, D., Wigglesworth, T. J. & Branda, N. R. Creating a reactive enediyne by using visible light: photocontrol of the Bergman cyclization. Angew. Chem. Int. Ed. 46, 8017–8019 (2007).

    CAS  Article  Google Scholar 

  14. 14.

    Erno, Z., Asadirad, A. M., Lemieux, V. & Branda, N. R. Using light and a molecular switch to ‘lock’ and ‘unlock’ the Diels–Alder reaction. Org. Biomol. Chem. 10, 2787–2792 (2012).

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Wilson, D. & Branda, N. R. Turning ‘on’ and ‘off’ a pyridoxal 5′-phosphate mimic using light. Angew. Chem. Int. Ed. 51, 5431–5434 (2012).

    CAS  Article  Google Scholar 

  16. 16.

    Göstl, R., Senf, A. & Hecht, S. Remote-controlling chemical reactions by light: towards chemistry with high spatio-temporal resolution. Chem. Soc. Rev. 43, 1982–1996 (2014).

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    Belowich, M. E. & Stoddart, J. F. Dynamic imine chemistry. Chem. Soc. Rev. 41, 2003–2024 (2012).

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Corbett, P. T. et al. Dynamic combinatorial chemistry. Chem. Rev. 106, 3652–3771 (2006).

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Lehn, J.-M. Perspectives in chemistry—aspects of adaptive chemistry and materials. Angew. Chem. Int. Ed. 54, 3276–3289 (2015).

    CAS  Article  Google Scholar 

  20. 20.

    Seebach, D. Methods of reactivity umpolung. Angew. Chem. Int. Ed. 18, 239–258 (1979).

    Article  Google Scholar 

  21. 21.

    Le Chatelier, H. Sur un énoncé général des lois des équilibres chimiques. Compte Rendus Acad. Sci. 99, 786–789 (1884).

    Google Scholar 

  22. 22.

    Chatterjee, M. N., Kay, E. R. & Leigh, D. A. Beyond switches: ratcheting a particle energetically uphill with a compartmentalized molecular machine. J. Am. Chem. Soc. 128, 4058–4073 (2006).

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    von Delius, M., Geertsema, E. M. & Leigh, D. A. A synthetic small molecule that can walk down a track. Nat. Chem. 2, 96–101 (2010).

    Article  CAS  Google Scholar 

  24. 24.

    Barrell, J., Campaña, A. G., von Delius, M., Geertsema, E. M. & Leigh, D. A. Light-driven transport of a molecular walker in either direction along a molecular track. Angew. Chem. Int. Ed. 50, 285–290 (2011).

    CAS  Article  Google Scholar 

  25. 25.

    Kay, E. R., Leigh, D. A. & Zerbetto, F. Synthetic molecular motors and mechanical machines. Angew. Chem. Int. Ed. 46, 72–191 (2007).

    CAS  Article  Google Scholar 

  26. 26.

    Cheng, C. et al. An artificial molecular pump. Nat. Nanotech. 10, 547–553 (2015).

    CAS  Article  Google Scholar 

  27. 27.

    Ragazzon, G., Baroncini, M., Silvi, S., Venturi, M. & Credi, A. Light-powered autonomous and directional molecular motion of a dissipative self-assembling system. Nat. Nanotech. 10, 70–75 (2015).

    CAS  Article  Google Scholar 

  28. 28.

    Erbas-Cakmak, S., Leigh, D. A., McTernan, C. T. & Nussbaumer, A. L. Artificial molecular machines. Chem. Rev. 115, 10081–10206 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Thordarson, P., Bijsterveld, E. J. A., Rowan, A. E. & Nolte, R. J. M. Epoxidation of polybutadiene by a topologically linked catalyst. Nature 424, 915–918 (2003).

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    He, Y. & Liu, D. R. Autonomous multistep organic synthesis in a single isothermal solution mediated by a DNA walker. Nat. Nanotech. 5, 778–782 (2010).

    CAS  Article  Google Scholar 

  31. 31.

    Wang, J. & Feringa, B. L. Dynamic control of chiral space in a catalytic asymmetric reaction using a molecular motor. Science 331, 1429–1432 (2011).

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Lewandowski, B. et al. Sequence-specific peptide synthesis by an artificial small-molecule machine. Science 339, 189–193 (2013).

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Zhao, H. et al. Reversible trapping and reaction acceleration within dynamically self-assembling nanoflasks. Nat. Nanotech. 11, 82–88 (2016).

    CAS  Article  Google Scholar 

  34. 34.

    Kassem, S. et al. Stereodivergent synthesis with a programmable molecular machine. Nature 549, 374–378 (2017).

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Göstl, R. & Hecht, S. Controlling covalent connection and disconnection with light. Angew. Chem. Int. Ed. 53, 8784–8787 (2014).

    Article  CAS  Google Scholar 

  36. 36.

    Frisch, H., Marschner, D., Goldmann, A. S. & Barner-Kowollik, C. Wavelength-gated dynamic covalent chemistry. Angew. Chem. Int. Ed. 57, 2036–2045 (2018).

    CAS  Article  Google Scholar 

  37. 37.

    Cordes, E. H. & Jencks, W. P. On the mechanism of Schiff base formation and hydrolysis. J. Am. Chem. Soc. 84, 832–837 (1962).

    CAS  Article  Google Scholar 

  38. 38.

    Sander, E. G. & Jencks, W. P. Equilibria for additions to the carbonyl group. J. Am. Chem. Soc. 90, 6154–6162 (1968).

    CAS  Article  Google Scholar 

  39. 39.

    Ciaccia, M., Cacciapaglia, R., Mencarelli, P., Mandolini, L. & Di Stefano, S. Fast transimination in organic solvents in the absence of proton and metal catalysts. A key to imine metathesis catalyzed by primary amines under mild conditions. Chem. Sci. 4, 2253–2261 (2013).

    CAS  Article  Google Scholar 

  40. 40.

    Ciaccia, M. & Di Stefano, S. Mechanisms of imine exchange reactions in organic solvents. Org. Biomol. Chem. 13, 646–654 (2015).

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Kathan, M. et al. Remote-controlling imine exchange kinetics with photoswitches to modulate self-healing in polysiloxane networks by light. Angew. Chem. Int. Ed. 55, 13882–13886 (2016).

    CAS  Article  Google Scholar 

  42. 42.

    Xu, Y., Su, T., Huang, Z. & Dong, G. Practical direct α-arylation of cyclopentanones by palladium/enamine cooperative catalysis. Angew. Chem. Int. Ed. 55, 2559–2563 (2016).

    CAS  Article  Google Scholar 

  43. 43.

    Eisenreich, F. et al. A photoswitchable catalyst system for remote-controlled (co)polymerization in situ. Nat. Catal. 1, 516–522 (2018).

    Article  Google Scholar 

  44. 44.

    Yamaguchi, T. et al. Photochromic reaction of diarylethenes having phenol moiety as an aryl ring. Bull. Chem. Soc. Jpn. 87, 528–538 (2014).

    CAS  Article  Google Scholar 

  45. 45.

    Dean, E. W. & Stark, D. D. A convenient method for the determination of water in petroleum and other organic emulsions. J. Ind. Eng. Chem. 12, 486–490 (1920).

    CAS  Article  Google Scholar 

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The authors thank S. Ihrig and J. Schwarz for upscaling the synthesis of phenol I. M.K. and F.E. are indebted to the Studienstiftung des deutschen Volkes and the Fonds der chemischen Industrie, respectively, for providing doctoral fellowships. Generous support by the European Research Council via ERC-2012-STG_308117 (Light4Function) is acknowledged.

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M.K., F.E., and C.J. carried out synthesis. M.K. and F.E. conducted optical spectroscopy. M.K. performed condensation/hydrolysis experiments. M.K. and A.D. analysed experiments via NMR spectroscopy. J.G. conducted computations. M.K., F.E., and S.H. conceived the idea, designed the study, and wrote the manuscript. All authors discussed the results and edited the manuscript.

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Correspondence to Stefan Hecht.

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Supplementary information

Synthetic and experimental procedures, computational, spectroscopic and mass spectrometric data, as well as additional experiments

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Kathan, M., Eisenreich, F., Jurissek, C. et al. Light-driven molecular trap enables bidirectional manipulation of dynamic covalent systems. Nature Chem 10, 1031–1036 (2018).

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