Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Terahertz time-domain spectroscopy and the quantitative monitoring of mechanochemical cocrystal formation

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Representations of involved molecules.
Figure 2: THz spectra and representation of the chain distortion leading to a THz absorption peak.
Figure 3: Results of quantification experiments.
Figure 4: SEM images of ground samples of (phen).(mes).

Similar content being viewed by others

References

  1. Chamberlain, J. M. Where optics meets electronics: Recent progress in decreasing the terahertz gap. Phil. Trans. R. Soc. Lond. A 362, 199–213 (2004).

    Article  CAS  Google Scholar 

  2. Han, J., Xu, H., Zhu, Z., Yu, X. & Li, W. Terahertz spectroscopy of naphthalene, alpha-naphthol, beta-naphthol, biphenyl and anthracene. Chem. Phys. Lett. 392, 348–351 (2004).

    Article  CAS  Google Scholar 

  3. Shah, B., Kakumanu, V. K. & Bansal, A. K. Analytical techniques for quantification of amorphous/crystalline phases in pharmaceutical solids. J. Pharm. Sci. 95, 1641–1665 (2006).

    Article  CAS  Google Scholar 

  4. Fischer, B., Hoffmann, M., Helm, H., Modjesch, G. & Jepsen, P. U. Chemical recognition in terahertz time-domain spectroscopy and imaging. Semicond. Sci. Technol. 20, S246–S253 (2005).

    Article  CAS  Google Scholar 

  5. Deibel, J. A., Wang, K., Escarra, M. D. & Mittleman, D. M. Enhanced coupling of terahertz radiation to cylindrical wire waveguides. Opt. Express 14, 279–290 (2006).

    Article  Google Scholar 

  6. Nguyen, K. L. et al. Three-dimensional imaging with a terahertz quantum cascade laser. Opt. Express 14, 2123–2129 (2006).

    Article  Google Scholar 

  7. Strachan, C. J. et al. Using terahertz pulsed spectroscopy to quantify pharmaceutical polymorphism and crystallinity. J. Pharm. Sci. 94, 837–846 (2005).

    Article  CAS  Google Scholar 

  8. Upadhya, P. C. et al. Characterisation of crystalline phase transformations in theophylline by time domain terahertz spectroscopy. Spectrosc. Lett. 39, 215–224 (2006).

    Article  CAS  Google Scholar 

  9. Liu, H.-B. & Zhang, X.-C. Dehydration kinetics of D-glucose monohydrate studied using THz time-domain spectroscopy. Chem. Phys. Lett. 429, 229–333 (2006).

    Article  CAS  Google Scholar 

  10. Vishweshwar, P., McMahon, J. A., Bis, J. A. & Zaworotko, M. J. Pharmaceutical co-crystals. J. Pharm. Sci. 95, 499–516 (2006).

    Article  CAS  Google Scholar 

  11. Sokolov, A. N., Friščić, T. & MacGillivray, L. R. Enforced face-to-face stacking of organic semiconductor building blocks within hydrogen-bonded molecular cocrystals. J. Am. Chem. Soc. 128, 2806–2807 (2006).

    Article  CAS  Google Scholar 

  12. Smolka, T., Schaller, T., Sustmann, R., Bläser, D. & Boese, R. Structure and properties of cocrystals of phenazine and fumaric, 2,3-dihydroxyfumaric and oxalic acid. J. Prakt. Chem. 342, 465–472 (2000).

    Article  CAS  Google Scholar 

  13. Batchelor, E., Klinowski, J. & Jones, W. Crystal engineering using co-crystallisation of phenazine with dicarboxylic acids. J. Mater. Chem. 10, 839–848 (2000).

    Article  CAS  Google Scholar 

  14. Steiner, T. The hydrogen bond in the solid state. Angew. Chem. Int. Edn 41, 48–76 (2002).

    Article  CAS  Google Scholar 

  15. Walmsley, S. H. Lattice vibrations and elastic constants of molecular crystals in the pair potential approximation. J. Chem. Phys. 48, 1438–1444 (1968).

    Article  CAS  Google Scholar 

  16. Day, G. M., Zeitler, J. A., Jones, W., Rades, T. & Taday, P. F. Understanding the influence of polymorphism on phonon spectra: Lattice dynamics calculations and terahertz spectroscopy of carbamazepine. J. Phys. Chem. B 110, 447–456 (2006).

    Article  CAS  Google Scholar 

  17. Luty, T. & Munn, R. W. Infrared intensities of lattice vibrations in molecular crystals. Chem. Phys. 43, 295–302 (1979).

    Article  CAS  Google Scholar 

  18. Trask, A. V. & Jones, W. Crystal engineering of organic cocrystals by the solid-state grinding approach. Top. Curr. Chem. 254, 41–70 (2005).

    Article  CAS  Google Scholar 

  19. Allis, D. G., Prokhorova, D. A. & Korter, T. M. Solid-state modeling of the terahertz spectrum of the high explosive HMX. J. Phys. Chem. A 110, 1951–1959 (2006).

    Article  CAS  Google Scholar 

Download references

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.

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tomislav Friščić
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Graeme M. Day
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lynn F. Gladden
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. William Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

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 to Lynn F. Gladden or William Jones.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary figures S1-S6 (PDF 2178 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmat1848

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing