Spatially resolved observation of crystal-face-dependent catalysis by single turnover counting


Catalytic processes on surfaces have long been studied by probing model reactions on single-crystal metal surfaces under high vacuum conditions. Yet the vast majority of industrial heterogeneous catalysis occurs at ambient or elevated pressures using complex materials with crystal faces, edges and defects differing in their catalytic activity. Clearly, if new or improved catalysts are to be rationally designed, we require quantitative correlations between surface features and catalytic activity—ideally obtained under realistic reaction conditions1,2,3. Transmission electron microscopy4,5,6 and scanning tunnelling microscopy7,8 have allowed in situ characterization of catalyst surfaces with atomic resolution, but are limited by the need for low-pressure conditions and conductive surfaces, respectively. Sum frequency generation spectroscopy can identify vibrations of adsorbed reactants and products in both gaseous and condensed phases9, but so far lacks sensitivity down to the single molecule level. Here we adapt real-time monitoring of the chemical transformation of individual organic molecules by fluorescence microscopy10,11,12 to monitor reactions catalysed by crystals of a layered double hydroxide immersed in reagent solution. By using a wide field microscope, we are able to map the spatial distribution of catalytic activity over the entire crystal by counting single turnover events. We find that ester hydrolysis proceeds on the lateral {} crystal faces, while transesterification occurs on the entire outer crystal surface. Because the method operates at ambient temperature and pressure and in a condensed phase, it can be applied to the growing number of liquid-phase industrial organic transformations to localize catalytic activity on and in inorganic solids. An exciting opportunity is the use of probe molecules with different size and functionality, which should provide insight into shape-selective or structure-sensitive catalysis13,14,15 and thus help with the rational design of new or more productive heterogeneous catalysts.

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Figure 1: Experimental set-up.
Figure 2: In situ wide field fluorescence micrographs of C-FDA transesterification on propyl amine-functionalized cover glasses.
Figure 3: Wide field images of catalytic reactions on individual LDH particles.
Figure 4: Analysis of single product molecules randomly diffusing on (0001) LDH surfaces after transesterification.


  1. 1

    Thomas, J. M. & Thomas, W. J. Principles and Practice of Heterogeneous Catalysis (Wiley-VCH, Weinheim, 1996)

    Google Scholar 

  2. 2

    Thomas, J. M. Catalysis and surface science at high resolution. Faraday Discuss. 105, 1–31 (1996)

    ADS  CAS  Article  Google Scholar 

  3. 3

    Ertl, G., Knözinger, H. & Weitkamp, J. Handbook of Heterogeneous Catalysis (Wiley-VCH, Weinheim, 2000)

    Google Scholar 

  4. 4

    Hansen, T. W. et al. Atomic-resolution in situ transmission electron microscopy of a promoter of a heterogeneous catalyst. Science 294, 1508–1510 (2001)

    ADS  CAS  Article  Google Scholar 

  5. 5

    Hansen, P. L. et al. Atom-resolved imaging of dynamic shape changes in supported copper nanocrystals. Science 295, 2053–2055 (2002)

    ADS  CAS  Article  Google Scholar 

  6. 6

    Helveg, S. et al. Atomic-scale imaging of carbon nanofibre growth. Nature 427, 426–429 (2004)

    ADS  CAS  Article  Google Scholar 

  7. 7

    Zambelli, T., Barth, J. V., Wintterlin, J. & Ertl, G. Complex pathways in dissociative adsorption of oxygen on platinum. Nature 390, 495–497 (1997)

    ADS  CAS  Article  Google Scholar 

  8. 8

    Wolff, J., Papathanasiou, A. G., Kevrekidis, I. G., Rotermund, H. H. & Ertl, G. Spatiotemporal addressing of surface activity. Science 294, 134–137 (2001)

    ADS  CAS  Article  Google Scholar 

  9. 9

    Dellwig, T., Rupprechter, G., Unterhalt, H. & Freund, H. J. Bridging the pressure and materials gap: High pressure sum frequency generation study on supported Pd nanoparticles. Phys. Rev. Lett. 85, 776–779 (2000)

    ADS  CAS  Article  Google Scholar 

  10. 10

    Lu, H. P., Xu, L. & Xie, X. S. Single-molecule enzymatic dynamics. Science 282, 1877–1882 (1998)

    ADS  CAS  Article  Google Scholar 

  11. 11

    Velonia, K. et al. Single-enzyme kinetics of CALB-catalyzed hydrolysis. Angew. Chem. Int. Edn Engl. 44, 560–564 (2005)

    CAS  Article  Google Scholar 

  12. 12

    Flomenbom, O. et al. Stretched exponential decay and correlations in the catalytic activity of fluctuating single lipase molecules. Proc. Natl Acad. Sci. USA 102, 2368–2372 (2005)

    ADS  CAS  Article  Google Scholar 

  13. 13

    Corma, A. Inorganic solid acids and their use in acid-catalyzed hydrocarbon reactions. Chem. Rev. 95, 559–614 (1995)

    CAS  Article  Google Scholar 

  14. 14

    Boudart, M., Aldag, A., Benson, J. E., Dougharty, N. A. & Harkins, C. G. On the specific activity of platinum catalysts. J. Catal. 6, 92–99 (1966)

    CAS  Article  Google Scholar 

  15. 15

    Bernasek, S. L., Siekhaus, W. J. & Somorjai, G. A. Molecular-beam study of hydrogen-deuterium exchange on low- and high-Miller-index platinum single-crystal surfaces. Phys. Rev. Lett. 30, 1202–1204 (1973)

    ADS  CAS  Article  Google Scholar 

  16. 16

    Fogg, A. M., Freij, A. J. & Parkinson, G. M. Synthesis and anion exchange chemistry of rhombohedral Li/Al layered double hydroxides. Chem. Mater. 14, 232–234 (2002)

    CAS  Article  Google Scholar 

  17. 17

    Cavani, F., Trifiro, F. & Vaccari, A. Hydrotalcite-type anionic clays: preparation, properties and applications. Catal. Today 11, 173–301 (1991)

    CAS  Article  Google Scholar 

  18. 18

    Cai, H., Hillier, A. C., Franklin, K. R., Nunn, C. C. & Ward, M. D. Nanoscale imaging of molecular adsorption. Science 266, 1551–1555 (1994)

    ADS  CAS  Article  Google Scholar 

  19. 19

    Sels, B. et al. Layered double hydroxides exchanged with tungstate as biomimetic catalysts for mild oxidative bromination. Nature 400, 855–857 (1999)

    ADS  CAS  Article  Google Scholar 

  20. 20

    Sels, B. F., De Vos, D. E. & Jacobs, P. A. Hydrotalcite-like anionic clays in catalytic organic reactions. Catal. Rev. 43, 443–488 (2001)

    CAS  Article  Google Scholar 

  21. 21

    Noji, H., Yasuda, R., Yoshida, M. & Kinosita, K. Direct observation of the rotation of F1-ATPase. Nature 386, 299–302 (1997)

    ADS  CAS  Article  Google Scholar 

  22. 22

    Roelofs, J. C. A. A., Lensveld, D. J., van Dillen, A. J. & de Jong, K. P. On the structure of activated hydrotalcites as solid base catalysts for liquid-phase aldol condensation. J. Catal. 203, 184–191 (2001)

    CAS  Article  Google Scholar 

  23. 23

    Abelló, S. et al. Aldol condensations over reconstructed Mg-Al hydrotalcites: structure–activity relationships related to the rehydration method. Chem. Eur. J. 11, 728–739 (2005)

    Article  Google Scholar 

  24. 24

    Corma, A., Iborra, S., Miquel, S. & Prim, J. Production of food emulsifiers, monoglycerides, by glycerolysis of fats with solid base catalysts. J. Catal. 173, 315–321 (1998)

    CAS  Article  Google Scholar 

  25. 25

    Engel, D. J., Malloy, T. P., & Nickl, P. K. Transesterification using metal oxide solid solutions as the basic catalyst. US Patent 5,350,879 (1993).

  26. 26

    Watanabe, Y. & Tatsumi, T. Hydrotalcite-type materials as catalysts for the synthesis of dimethyl carbonate from ethylene carbonate and methanol. Micropor. Mesopor. Mater. 22, 399–407 (1998)

    CAS  Article  Google Scholar 

  27. 27

    Abelló, S. et al. Aldol condensations over reconstructed Mg–Al hydrotalcites: structure–activity relationships related to the rehydration method. Chem. Eur. J. 11, 728–739 (2005)

    Article  Google Scholar 

  28. 28

    Hellriegel, C., Kirstein, J. & Bräuchle, C. Tracking of single molecules as a powerful method to characterize diffusivity of organic species in mesoporous materials. N. J. Phys. 7, 1–14 (2005)

    Article  Google Scholar 

  29. 29

    Hell, S. W. Toward fluorescence nanoscopy. Nature Biotechnol. 21, 1347–1355 (2003)

    CAS  Article  Google Scholar 

  30. 30

    Martens, J. A. et al. Evidences for pore mouth and key–lock catalysis in hydroisomerization of long n-alkanes over 10-ring tubular pore bifunctional zeolites. Catal. Today 65, 111–116 (2001)

    CAS  Article  Google Scholar 

  31. 31

    Serna, C. J., Rendon, J. L. & Iglesias, J. E. Crystal-chemical study of layered [Al2Li(OH)6]+X-.nH2O. Clays Clay Miner. 30, 180–184 (1982)

    ADS  CAS  Article  Google Scholar 

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M.B.J.R. thanks the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen) for a fellowship, B.F.S. thanks the FWO-Flanders for a post-doctoral fellowship and the KUL for a guest professor position. This work was performed within the framework of the IAP-V-03 programme ‘Supramolecular Chemistry and Catalysis’ of the Belgian Federal government and of GOA-2/01.

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Correspondence to Dirk E. De Vos or Johan Hofkens.

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Supplementary information

Supplementary Video 1

Wide field fluorescence images of C-FDA transesterification on a coverglass functionalized with a 1:10,000 DMAPTS:PTS mixture. (AVI 3484 kb)

Supplementary Video 2

Wide field fluorescence image of the catalytic transesterification of C-FDA on an individual LDH particle. (AVI 9700 kb)

Supplementary Video 3

Wide field fluorescence image of the catalytic transesterification of FDA on an individual LDH particle. (AVI 3420 kb)

Supplementary Video 4

Detail of the diffusion of single 5-carboxyfluorescein product molecules on the basal plane of an LDH. (AVI 2007 kb)

Supplementary Notes

This file contains Supplementary Data on the use of fluorescence microscopy for in situ study of organic transformations on mordenite zeolites. This file also contains a Supplementary Discussion and Supplementary Figures. (DOC 490 kb)

Supplementary Legends

Text to accompany the above Supplementary Videos. (DOC 30 kb)

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Roeffaers, M., Sels, B., Uji-i, H. et al. Spatially resolved observation of crystal-face-dependent catalysis by single turnover counting. Nature 439, 572–575 (2006).

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