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X-ray analysis on the nanogram to microgram scale using porous complexes

Nature volume 495, pages 461–466 (2013)Cite this article

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A Corrigendum to this article was published on 21 August 2013

Abstract

X-ray single-crystal diffraction (SCD) analysis has the intrinsic limitation that the target molecules must be obtained as single crystals. Here we report a protocol for SCD analysis that does not require the crystallization of the sample. In our method, tiny crystals of porous complexes are soaked in a solution of the target, such that the complexes can absorb the target molecules. Crystallographic analysis clearly determines the absorbed guest structures along with the host frameworks. Because the SCD analysis is carried out on only one tiny crystal of the complex, the required sample mass is of the nanogram–microgram order. We demonstrate that as little as about 80 nanograms of a sample is enough for the SCD analysis. In combination with high-performance liquid chromatography, our protocol allows the direct characterization of multiple fractions, establishing a prototypical means of liquid chromatography SCD analysis. Furthermore, we unambiguously determined the structure of a scarce marine natural product using only 5 micrograms of the compound.

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Figure 1: X-ray crystallographic observation of liquid guest molecules using crystalline sponges.
Figure 2: Nanogram-scale guest inclusion with a crystal of crystalline sponge3.
Figure 3: Crystal structures of a variety of guests determined using a one-crystal-scale inclusion protocol.
Figure 4: The crystal structure of a chiral guest, santonin, trapped in a crystalline sponge.
Figure 5: LC–SCD analysis of natural flavonoids.
Figure 6: Structural determination of miyakosyne A.

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Acknowledgements

This research was supported by Grants-in-Aid for Specially Promoted Research (24000009) and Young Scientists (B) (23750146), and by the CREST project of the Japan Science and Technology Agency. The experiment involving X-ray crystallography with 80 ng of guest molecules was performed using VariMax optics with a RAPID image plate detector system, courtesy of Rigaku Corporation. We thank M. Yamasaki and H. Sato for support for X-ray measurements.

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Authors and Affiliations

  1. Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan,

    Yasuhide Inokuma, Shota Yoshioka, Junko Ariyoshi, Tatsuhiko Arai & Makoto Fujita

  2. Laboratory of Aquatic Natural Products Chemistry, Graduate School of Agricultural and Life Science, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan ,

    Yuki Hitora, Kentaro Takada & Shigeki Matsunaga

  3. Department of Chemistry, NanoScience Center, University of Jyväskylä, PO Box 35, 40014 Jyväskylä, Finland,

    Kari Rissanen

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  1. Yasuhide Inokuma
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Contributions

Y.I. and M.F. designed the project, analysed results and wrote the manuscript. S.Y., J.A. and T.A. performed the experimental work and crystallographic analysis. Y.H., S.M. and K.T. selected and provided a natural product sample for analysis. K.R. confirmed the validity of the X-ray crystallographic analysis of all data.

Corresponding author

Correspondence to Makoto Fujita.

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The authors declare no competing financial interests.

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 910380, 910381, 910382, 910383, 910384, 910385, 910386, 910387, 910388, 910389, 910390, 910391, 910392, 910393 and 910394. 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 Supplementary Methods, Supplementary Text and Data Supplementary Figures 1-5 and additional references. (PDF 3503 kb)

Supplementary Data

This file contains the crystallographic data. This file was added online on 8 April, 2013. (TXT 774 kb)

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Inokuma, Y., Yoshioka, S., Ariyoshi, J. et al. X-ray analysis on the nanogram to microgram scale using porous complexes. Nature 495, 461–466 (2013). https://doi.org/10.1038/nature11990

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