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X-ray observation of a transient hemiaminal trapped in a porous network

Abstract

X-ray crystallography is the method of choice for the direct structural analysis of crystalline compounds1. Extending its use to the in situ mapping of chemical transformations could provide valuable insights, as illustrated by time-resolved X-ray crystallography studies2,3; however, the transient nature of unstable reaction intermediates often poses a significant challenge. It has recently been demonstrated that standard chemical reactions can occur within the pores of porous coordination networks4,5,6 and that the robust crystallinity of these networks facilitates in situ X-ray analysis of the adducts and products7,8,9,10,11. Here we show that such systems even enable X-ray observations of reaction intermediates that are usually transient and non-isolable. Our proof-of-concept demonstration examines the simple and ubiquitous reaction between an amine and an aldehyde, which normally form a very short-lived hemiaminal that then yields the Schiff-base product. The mechanism of this reaction has been exhaustively examined, but the hemiaminal intermediate has only rarely been observed12,13,14,15,16. We first determine the structure of a porous network with an aromatic amine embedded in it, then diffuse an aldehyde substrate into the material to transform the amine into a hemiaminal intermediate that is kinetically trapped and thus amenable to X-ray analysis, and finally raise the temperature of the system to obtain the imine product and determine its structure. These results establish that porous network materials provide a means of obtaining sequential X-ray-based snapshots of the structural transformations that occur during chemical reactions.

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Figure 1: A reaction profile of imine formation.
Figure 2: Preparation of porous coordination network {[(ZnI2)3(2)2(3)]· x (G)}n (1; G = ethyl acetate, x = 4).
Figure 3: Direct crystallographic observation of imine formation from acetaldehyde and embedded 1-aminotriphenylene within the pores of 1.
Figure 4: Experimental device for the in situ hemiaminal formation in the crystal of 1.
Figure 5: Disorder of embedded amine 3 before the reaction.

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References

  1. 1

    Ohashi, Y. in Models, Mysteries and Magic of Molecules (eds Boeyens, J. C. A. & Ogilvie, J. F.) 109–113 (Springer, 2008)

    Book  Google Scholar 

  2. 2

    Coppens, P., Vorontsov, I. I., Graber, T., Gembicky, M. & Kovalevsky, A. Y. The structure of short-lived excited states of molecular complexes by time-resolved X-ray diffraction. Acta Crystallogr. A 61, 162–172 (2005)

    ADS  PubMed  Article  Google Scholar 

  3. 3

    Moffat, K. Time-resolved biochemical crystallography: a mechanistic perspective. Chem. Rev. 101, 1569–1581 (2001)

    CAS  PubMed  Article  Google Scholar 

  4. 4

    Batten, S. R. & Robson, R. Interpenetrating nets: ordered, periodic entanglement. Angew. Chem. Int. Ed. 37, 1460–1494 (1998)

    Article  Google Scholar 

  5. 5

    Eddaoudi, M. et al. Modular chemistry: secondary building units as a basis for the design of highly porous and robust metal-organic carboxylate frameworks. Acc. Chem. Res. 34, 319–330 (2001)

    CAS  PubMed  Article  Google Scholar 

  6. 6

    Kitagawa, S., Kitaura, R. & Noro, S. Functional porous coordination polymers. Angew. Chem. Int. Ed. 43, 2334–2375 (2004)

    CAS  Article  Google Scholar 

  7. 7

    Haneda, T., Kawano, M., Kawamichi, T. & Fujita, M. Direct observation of the labile imine formation through single-crystal-to-single-crystal reactions in the pores of a porous coordination network. J. Am. Chem. Soc. 130, 1578–1579 (2008)

    CAS  PubMed  Article  Google Scholar 

  8. 8

    Kawamichi, T., Kodama, T., Kawano, M. & Fujita, M. Single-crystalline molecular flasks: chemical transformation with bulky reagents in the pores of porous coordination networks. Angew. Chem. Int. Ed. 47, 8030–8032 (2008)

    CAS  Article  Google Scholar 

  9. 9

    Costa, J. S. et al. Chemical modification of a bridging ligand inside a metal–organic framework while maintaining the 3D structure. Eur. J. Inorg. Chem. 1551–1554 (2008)

    Article  Google Scholar 

  10. 10

    Burrows, A. D., Frost, C. G., Mahon, M. F. & Richardson, C. Post-synthetic modification of tagged metal–organic frameworks. Angew. Chem. Int. Ed. 47, 8482–8486 (2008)

    CAS  Article  Google Scholar 

  11. 11

    Wang, Z. & Cohen, S. M. Postsynthetic modification of metal–organic frameworks. Chem. Soc. Rev. 38, 1315–1329 (2009)

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. 12

    Forlani, L., Marianucci, E. & Todesco, P. E. 1H nuclear magnetic resonance evidence for tetrahedral intermediates in the reactions between aromatic carbonyl groups and aliphatic amines. J. Chem. Res. Synop. 126–127 (1984)

  13. 13

    Chudek, J. A., Foster, R. & Young, D. 13C nuclear magnetic resonance studies of the products of reaction of acetaldehyde and of simple ketones in liquid ammonia, in hydrazine hydrate, and in some substituted hydrazine solutions. J. Chem. Soc., Perkin Trans. 2 1285–1289 (1985)

  14. 14

    Evans, D. A., Borg, G. & Scheidt, K. A. Remarkably stable tetrahedral intermediates: carbinols from nucleophilic additions to N-acylpyrroles. Angew. Chem. Int. Ed. 41, 3188–3191 (2002)

    CAS  Article  Google Scholar 

  15. 15

    Iwasawa, T., Hooley, R. J. & Rebek, J. Stabilization of labile carbonyl addition intermediates by a synthetic receptor. Science 317, 493–496 (2007)

    ADS  CAS  PubMed  Article  Google Scholar 

  16. 16

    Hooley, R. J., Iwasawa, T. & Rebek, J. detection of reactive tetrahedral intermediates in a deep cavity and with an introverted functionality. J. Am. Chem. Soc. 129, 15330–15339 (2007)

    CAS  PubMed  Article  Google Scholar 

  17. 17

    Heine, A. et al. Observation of covalent intermediates in an enzyme mechanism at atomic resolution. Science 294, 369–374 (2001)

    ADS  CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. 18

    Thorell, S., Schürmann, M., Georg, A., Sprenger, G. A. & Schneider, G. Crystal structure of decameric fructose-6-phosphate aldolase from Escherichia coli reveals inter-subunit helix swapping as a structural basis for assembly differences in the transaldolase family. J. Mol. Biol. 319, 161–171 (2002)

    CAS  PubMed  Article  Google Scholar 

  19. 19

    Lorentzen, E., Siebers, B., Hensel, R. & Pohl, E. Mechanism of the Schiff base forming fructose-1,6-bisphosphate aldolase: structural analysis of reaction intermediates. Biochemistry 44, 4222–4229 (2005)

    CAS  PubMed  Article  Google Scholar 

  20. 20

    Kawano, M., Kawamichi, T., Haneda, T., Kojima, T. & Fujita, M. The modular synthesis of functional porous coordination networks. J. Am. Chem. Soc. 129, 15418–15419 (2007)

    CAS  PubMed  Article  Google Scholar 

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Acknowledgements

This research was supported by the CREST project of the Japan Science and Technology Agency, of which M.F. is the principal investigator, and also in part by KAKENHI, the Japan Society for the Promotion of Science, the Global COE Program (Chemistry Innovation through Cooperation of Science and Engineering), MEXT, Japan, and Koei Chemical Co. Ltd. This work has been approved by the Photon Factory Program Advisory Committee.

Author Contributions M.K. and M.F. designed the project, analysed the results and wrote the manuscript. T.K. and T.H. performed the experimental work.

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Correspondence to Masaki Kawano or Makoto Fujita.

Additional information

The X-ray crystallographic coordinates for structures reported in this paper have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 725638 (1), CCDC 725639 (6) and CCDC 725640 (7). These data can be obtained free of charge from the Cambridge Crystallographic Data Centre (http://www.ccdc.cam.ac.uk/data_request/cif).

Supplementary information

Supplementary Information

This file contains Crystallographic Data for 1, 6 and 7 and Supplementary Figures for S1-S9 with Legends. (PDF 3842 kb)

Supplementary Data

This file is the Crystallographic Information File (CIF) for the coordination networks 1, 4, and 5 and it shows that the molecular modelling software reproduces the crystal structures. (TXT 165 kb)

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Kawamichi, T., Haneda, T., Kawano, M. et al. X-ray observation of a transient hemiaminal trapped in a porous network. Nature 461, 633–635 (2009). https://doi.org/10.1038/nature08326

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