Terahertz time-domain spectroscopy and the quantitative monitoring of mechanochemical cocrystal formation (original) (raw)

Nature Materials volume 6, pages 206–209 (2007) Cite this article

Abstract

Terahertz (THz) radiation probes intermolecular interactions through crystal lattice vibrations, allowing the characterization of solid materials1,2. Thus, THz spectroscopy is a promising alternative to mainstream solid-state analytical tools such as X-ray diffraction or thermal analysis3. The method provides the benefits of online measurement4, remote sampling5 and three-dimensional imaging6, all of which are attractive for quality control and security applications. In the context of pharmaceutical solids, THz spectroscopy can differentiate and quantify different forms of active pharmaceutical ingredients7,8. Here, we apply this technique to monitor a dynamic process involving two molecular crystals9. In particular, we follow the mechanochemical construction of a two-component cocrystal10,11,12 by grinding together phenazine (phen) and mesaconic acid (mes)13. To rationalize the observed changes in the spectra, we conduct lattice dynamics calculations that lead to the tentative assignment of at least one feature in the cocrystal THz spectrum.

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Figure 1: Representations of involved molecules.

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Figure 2: THz spectra and representation of the chain distortion leading to a THz absorption peak.

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Figure 3: Results of quantification experiments.

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Figure 4: SEM images of ground samples of (phen).(mes).

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Acknowledgements

We are grateful to the Research Councils UK ‘Basic Technology Programme’ for funding aspects of this work. K.L.N. thanks the Gates Cambridge Trust for financial support. T.F. acknowledges the Pfizer Institute for Pharmaceutical Materials Science for funding. G.M.D. thanks the Royal Society for funding.

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Authors and Affiliations

  1. Department of Chemical Engineering, University of Cambridge, Pembroke Street, Cambridge CB2 3RA, UK
    K. Lien Nguyen & Lynn F. Gladden
  2. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
    Tomislav Friščić, Graeme M. Day & William Jones

Authors

  1. K. Lien Nguyen
  2. Tomislav Friščić
  3. Graeme M. Day
  4. Lynn F. Gladden
  5. William Jones

Contributions

All authors contributed to the analysis and interpretation of the results. Sample preparation and measurements were carried out by K.L.N. and T.F. The computational work of predicting and interpreting the form of the spectra was done by G.M.D.

Corresponding authors

Correspondence toLynn F. Gladden or William Jones.

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The authors declare no competing financial interests.

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Lien Nguyen, K., Friščić, T., Day, G. et al. Terahertz time-domain spectroscopy and the quantitative monitoring of mechanochemical cocrystal formation.Nature Mater 6, 206–209 (2007). https://doi.org/10.1038/nmat1848

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