Modular and predictable assembly of porous organic molecular crystals


Nanoporous molecular frameworks1,2,3,4,5,6,7 are important in applications such as separation, storage and catalysis. Empirical rules exist for their assembly but it is still challenging to place and segregate functionality in three-dimensional porous solids in a predictable way. Indeed, recent studies of mixed crystalline frameworks suggest a preference for the statistical distribution of functionalities throughout the pores7 rather than, for example, the functional group localization found in the reactive sites of enzymes8. This is a potential limitation for ‘one-pot’ chemical syntheses of porous frameworks from simple starting materials. An alternative strategy is to prepare porous solids from synthetically preorganized molecular pores9,10,11,12,13,14,15. In principle, functional organic pore modules could be covalently prefabricated and then assembled to produce materials with specific properties. However, this vision of mix-and-match assembly is far from being realized, not least because of the challenge in reliably predicting three-dimensional structures for molecular crystals, which lack the strong directional bonding found in networks. Here we show that highly porous crystalline solids can be produced by mixing different organic cage modules that self-assemble by means of chiral recognition. The structures of the resulting materials can be predicted computationally16,17, allowing in silico materials design strategies18. The constituent pore modules are synthesized in high yields on gram scales in a one-step reaction. Assembly of the porous co-crystals is as simple as combining the modules in solution and removing the solvent. In some cases, the chiral recognition between modules can be exploited to produce porous organic nanoparticles. We show that the method is valid for four different cage modules and can in principle be generalized in a computationally predictable manner based on a lock-and-key assembly between modules.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Modular assembly of porous organic cages.
Figure 2: Window-to-window assembly results in porosity.
Figure 3: Three-dimensional cage assembly can be predicted computationally.
Figure 4: Module assembly in solution can be used to produce porous nanoparticles.


  1. 1

    Kondo, M., Yoshitomi, T., Seki, K., Matsuzaka, H. & Kitagawa, S. Three-dimensional framework with channeling cavities for small molecules: {M2(4,4-bpy)3(NO3)4·xH2O}n (M = Co, Ni, Zn). Angew. Chem. Int. Edn Engl. 36, 1725–1727 (1997)

    CAS  Article  Google Scholar 

  2. 2

    Li, H., Eddaoudi, M., O’Keeffe, M. & Yaghi, O. M. Design and synthesis of an exceptionally stable and highly porous metal–organic framework. Nature 402, 276–279 (1999)

    CAS  ADS  Article  Google Scholar 

  3. 3

    Eddaoudi, M. et al. Systematic design of pore size and functionality in isoreticular MOFs and their application in methane storage. Science 295, 469–472 (2002)

    CAS  ADS  Article  Google Scholar 

  4. 4

    Zhao, X. B. et al. Hysteretic adsorption and desorption of hydrogen by nanoporous metal-organic frameworks. Science 306, 1012–1015 (2004)

    CAS  ADS  Article  Google Scholar 

  5. 5

    Férey, G. et al. A chromium terephthalate-based solid with unusually large pore volumes and surface area. Science 309, 2040–2042 (2005)

    ADS  Article  Google Scholar 

  6. 6

    Côté, A. P. et al. Porous, crystalline, covalent organic frameworks. Science 310, 1166–1170 (2005)

    ADS  Article  Google Scholar 

  7. 7

    Deng, H. X. et al. Multiple functional groups of varying ratios in metal-organic frameworks. Science 327, 846–850 (2010)

    CAS  ADS  Article  Google Scholar 

  8. 8

    Nureki, O. et al. Enzyme structure with two catalytic sites for double-sieve selection of substrate. Science 280, 578–582 (1998)

    CAS  ADS  Article  Google Scholar 

  9. 9

    Barbour, L. J. Crystal porosity and the burden of proof. Chem. Commun. 1163–1168 (2006)

  10. 10

    Atwood, J. L., Barbour, L. J. & Jerga, A. Storage of methane and freon by interstitial van der Waals confinement. Science 296, 2367–2369 (2002)

    CAS  ADS  Article  Google Scholar 

  11. 11

    Tranchemontagne, D. J. L., Ni, Z., O’Keeffe, M. & Yaghi, O. M. Reticular chemistry of metal-organic polyhedra. Angew. Chem. Int. Ed. 47, 5136–5147 (2008)

    CAS  Article  Google Scholar 

  12. 12

    Tozawa, T. et al. Porous organic cages. Nature Mater. 8, 973–978 (2009)

    CAS  ADS  Article  Google Scholar 

  13. 13

    Bezzu, C. G., Helliwell, M., Warren, J. E., Allan, D. R. & McKeown, N. B. Heme-like coordination chemistry within nanoporous molecular crystals. Science 327, 1627–1630 (2010)

    CAS  ADS  Article  Google Scholar 

  14. 14

    Jones, J. T. A. et al. On–off porosity switching in a molecular organic solid. Angew. Chem. Int. Ed. 50, 749–753 (2011)

    CAS  Article  Google Scholar 

  15. 15

    Mastalerz, M., Schneider, M. W., Oppel, I. M. & Presly, O. A salicylbisimine cage compound with high surface area and selective CO2/CH4 adsorption. Angew. Chem. Int. Ed. 50, 1046–1055 (2011)

    CAS  Article  Google Scholar 

  16. 16

    Day, G. M. et al. Significant progress in predicting the crystal structures of small organic molecules – a report on the fourth blind test. Acta Crystallogr. B 65, 107–125 (2009)

    CAS  Article  Google Scholar 

  17. 17

    Price, S. L. Computed crystal energy landscapes for understanding and predicting organic crystal structures and polymorphism. Acc. Chem. Res. 42, 117–126 (2009)

    CAS  Article  Google Scholar 

  18. 18

    Jansen, M., Doll, K. & Schön, J. C. Addressing chemical diversity by employing the energy landscape concept. Acta Crystallogr. A 66, 518–534 (2010)

    CAS  ADS  Article  Google Scholar 

  19. 19

    Ingleson, M. J., Barrio, J. P., Guilbaud, J. B., Khimyak, Y. Z. & Rosseinsky, M. J. Framework functionalisation triggers metal complex binding. Chem. Commun. 2680–2682 (2008)

  20. 20

    Desiraju, G. R. Supramolecular synthons in crystal engineering – a new organic-synthesis. Angew. Chem. Int. Edn Engl. 34, 2311–2327 (1995)

    CAS  Article  Google Scholar 

  21. 21

    Simard, M., Su, D. & Wuest, J. D. Use of hydrogen bonds to control molecular aggregation. Self-assembly of three-dimensional networks with large chambers. J. Am. Chem. Soc. 113, 4696–4698 (1991)

    CAS  Article  Google Scholar 

  22. 22

    Wuest, J. D. Engineering crystals by the strategy of molecular tectonics. Chem. Commun. 5830–5837 (2005)

  23. 23

    Hof, F., Craig, S. L., Nuckolls, C. & Rebek, J. Molecular encapsulation. Angew. Chem. Int. Ed. 41, 1488–1508 (2002)

    CAS  Article  Google Scholar 

  24. 24

    McKeown, N. B. Nanoporous molecular crystals. J. Mater. Chem. 20, 10588–10597 (2010)

    CAS  Article  Google Scholar 

  25. 25

    Wheeler, K. A., Grove, R. C., Davis, R. E. & Kassel, W. S. Quasiracemic materials – rediscovering Pasteur’s quasiracemates. Angew. Chem. Int. Ed. 47, 78–81 (2008)

    CAS  Article  Google Scholar 

  26. 26

    Dance, I. & Scudder, M. Supramolecular motifs: sextuple aryl embraces in crystalline M(2,2′-bipy)3 and related complexes. Dalton Trans. 1341–1350 (1998)

  27. 27

    Day, G. M., Motherwell, W. D. S. & Jones, W. Beyond the isotropic atom model in crystal structure prediction of rigid molecules: atomic multipoles versus point charges. Cryst. Growth Des. 5, 1023–1033 (2005)

    CAS  Article  Google Scholar 

  28. 28

    Price, S. L. et al. Modelling organic crystal structures using distributed multipole and polarizability-based model intermolecular potentials. Phys. Chem. Chem. Phys. 12, 8478–8490 (2010)

    CAS  Article  Google Scholar 

  29. 29

    Karamertzanis, P. G. & Pantelides, C. C. Ab initio crystal structure prediction. II. Flexible molecules. Mol. Phys. 105, 273–291 (2007)

    CAS  ADS  Article  Google Scholar 

  30. 30

    Görbitz, C. H., Dalhus, B. & Day, G. M. Pseudoracemic amino acid complexes: blind predictions for flexible two-component crystals. Phys. Chem. Chem. Phys. 12, 8466–8477 (2010)

    Article  Google Scholar 

  31. 31

    VandeVondele, J. et al. Quickstep: fast and accurate density functional calculations using a mixed Gaussian and plane waves approach. Comp. Phys. Comm. 167, 103–108 (2005)

    CAS  ADS  Article  Google Scholar 

  32. 32

    Grimme, S., Antony, J., Ehrlich, S. & Krieg, H. A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu. J. Chem. Phys. 132, 154104 (2010)

    ADS  Article  Google Scholar 

Download references


We thank EPSRC (EP/H000925/1) and the Dutch Polymer Institute for funding. The UK national high-performance computing service HECToR was used for this work through the HPC Materials Chemistry Consortium (EPSRC grant EP/F067496. A.I.C. and G.M.D. are Royal Society Wolfson Merit Award holder and A.T. and G.M.D. are Royal Society University Research Fellows.

Author information




J.T.A.J. prepared cage modules and co-crystals thereof, contributed to powder X-ray diffraction analysis, carried out high-throughput co-crystallization screening experiments and generally coordinated the experimental work; T.H. prepared cage modules and co-crystals and the nanocrystals of (3-S, 3-R), and carried out microscopy; J.T.A.J. and T.H. did the gas sorption analysis; X.W. synthesized module 5; D.J.A. contributed to the cage synthesis; J.B., M.S., S.Y.C. and A.S. performed the crystallography; K.E.J., A.T., F.C. and B.S. performed molecular and periodic simulations, in particular the DFT studies; G.M.D. led the crystal structure prediction; and A.I.C. designed the project and wrote the paper with contributions from all co-authors.

Corresponding author

Correspondence to Andrew I. Cooper.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

The file contains Supplementary Text, Supplementary Table 1, Supplementary Figures 1-26 with legends and additional references. (PDF 5033 kb)

Supplementary Movie 1

The movie shows the effect of mixing a solution of cage 3-R with an equivalent solution of cage 3-S - see ‘Figure 27’ legend in Supplementary Information file. (MOV 2730 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Jones, J., Hasell, T., Wu, X. et al. Modular and predictable assembly of porous organic molecular crystals. Nature 474, 367–371 (2011).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.