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.

  • Article
  • Published:

Palladium-mediated intracellular chemistry

Nature Chemistry volume 3, pages 239–243 (2011)Cite this article

Subjects

Abstract

Many important intracellular biochemical reactions are modulated by transition metals, typically in the form of metalloproteins. The ability to carry out selective transformations inside a cell would allow researchers to manipulate or interrogate innumerable biological processes. Here, we show that palladium nanoparticles trapped within polystyrene microspheres can enter cells and mediate a variety of Pd0-catalysed reactions, such as allylcarbamate cleavage and Suzuki–Miyaura cross-coupling. The work provides the basis for the customization of heterogeneous unnatural catalysts as tools to carry out artificial chemistries within cells. Such in cellulo synthesis has potential for a plethora of applications ranging from cellular labelling to synthesis of modulators or inhibitors of cell function.

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: Synthesis and characterization of Pd0 microspheres.
Figure 2: Pd0-mediated allylcarbamate cleavage within HeLa cells.
Figure 3: Pd0-mediated Suzuki–Miyaura cross-coupling within HeLa cells.

Similar content being viewed by others

References

  1. Silverman, R. E. Organic Chemistry of Enzyme-Catalyzed Reactions 2nd edn (Academic Press, 2002).

    Google Scholar 

  2. Bugg, T. Introduction to Enzyme and Coenzyme Chemistry 2nd edn (Wiley-Blackwell, 2004).

    Book  Google Scholar 

  3. Lippard, S. J. & Berg, J. M. Principles of Bioinorganic Chemistry (University Science Books, 1994).

    Google Scholar 

  4. Andreini, C., Bertini, I., Cavallaro, G., Holliday, G. L. & Thornton, J. M. Metal ions in biological catalysis: from enzyme databases to general principles. J. Biol. Inorg. Chem. 13, 1205–1218 (2008).

    Article  CAS  Google Scholar 

  5. Waldron, K. J., Rutherford, J. C., Ford, D. & Robinson, N. J. Metalloproteins and metal sensing. Nature 460, 823–830 (2009).

    Article  CAS  Google Scholar 

  6. Costas, M., Mehn, M. P., Jensen, M. P. & Que, L Jr. Dioxygen activation at mononuclear nonheme iron active sites: enzymes, models, and intermediates. Chem. Rev. 104, 939–986 (2004).

    Article  CAS  Google Scholar 

  7. Tshuva, E. Y. & Lippard, S. J. Synthetic models for non-heme carboxylate-bridged diiron metalloproteins: strategies and tactics. Chem. Rev. 104, 987–1012 (2004).

    Article  CAS  Google Scholar 

  8. Lippard, S. J. The inorganic side of chemical biology. Nat. Chem. Biol. 2, 504–507 (2006).

    Article  CAS  Google Scholar 

  9. Tolman, W. B. & Spencer, D. J. E. New advances in ligand design for synthetic modeling of metalloprotein active sites. Curr. Opin. Chem. Biol. 5, 188–195 (2001).

    Article  CAS  Google Scholar 

  10. Xing, G. & DeRose, V. J. Designing metal–peptide models for protein structure and function. Curr. Opin. Chem. Biol. 5, 196–200 (2001).

    Article  CAS  Google Scholar 

  11. Baltzer, L. & Nilsson, J. Emerging principles of de novo catalyst design. Curr. Opin. Biotech. 12, 355–360 (2001).

    Article  CAS  Google Scholar 

  12. Lu, Y. Biosynthetic inorganic chemistry. Angew. Chem. Int. Ed. 45, 5588–5601 (2006).

    Article  CAS  Google Scholar 

  13. Haas, K. L. & Franz, K. J. Application of metal coordination chemistry to explore and manipulate cell biology. Chem. Rev. 109, 4921–4960 (2009).

    Article  CAS  Google Scholar 

  14. Domaille, D. W., Que, E. L. & Chang, C. J. Synthetic fluorescent sensors for studying the cell biology of metals. Nat. Chem. Biol. 4, 168–175 (2008).

    Article  CAS  Google Scholar 

  15. McRae, R., Bagchi, P., Sumalekshmy, S. & Fahrni, C. J. In situ imaging of metals in cells and tissues. Chem. Rev. 109, 4780–4827 (2009).

    Article  CAS  Google Scholar 

  16. Liang, G., Ren, H. & Rao, J. A biocompatible condensation reaction for controlled assembly of nanostructures in living cells. Nature Chem. 2, 54–60 (2010).

    Article  CAS  Google Scholar 

  17. Santra, M., Ko, S.-K., Shin, I. & Ahn, K. H. Fluorescent detection of palladium species with an O-propargylated fluorescein. Chem. Commun. 46, 3964–3966 (2010).

    Article  CAS  Google Scholar 

  18. Streu, C. & Meggers, E. Ruthenium-induced allylcarbamate cleavage in living cells. Angew. Chem. Int. Ed. 45, 5645–5648 (2006).

    Article  CAS  Google Scholar 

  19. Bruijnincx, P. C. A. & Sadler, P. J. New trends for metal complexes with anticancer activity. Curr. Opin. Chem. Biol. 12, 197–206 (2008).

    Article  CAS  Google Scholar 

  20. Abu-Surrah, A. S. & Kettunen, M. Platinum group antitumor chemistry: design and development of new anticancer drugs complementary to cisplatin. Curr. Med. Chem. 13, 1337–1357 (2006).

    Article  CAS  Google Scholar 

  21. Negishi, E. I. Handbook of Organopalladium Chemistry for Organic Synthesis (Wiley-Interscience, 2002).

    Book  Google Scholar 

  22. Sanchez-Martin, R. M. et al. Bead-based cellular analysis, sorting and multiplexing. ChemBioChem 6, 1341–1345 (2005).

    Article  CAS  Google Scholar 

  23. Sanchez-Martin, R. M., Cuttle, M., Mittoo, S. & Bradley, M. Microsphere-based real-time calcium sensing. Angew. Chem. Int. Ed. 45, 5472–5474 (2006).

    Article  CAS  Google Scholar 

  24. Alexander, L. M., Sanchez-Martin, R. M. & Bradley M. Knocking (anti)-sense into cells: the microsphere approach to gene silencing. Bioconjug. Chem. 20, 422–426 (2009).

    Article  CAS  Google Scholar 

  25. Sanchez-Martin, R. M. et al. Microsphere-mediated protein delivery into cells. ChemBioChem 10, 1453–1456 (2009).

    Article  CAS  Google Scholar 

  26. Alexander, L. M. et al. Investigation of microsphere-mediated cellular delivery by chemical, microscopic and gene expression analysis. Mol. BioSyst. 6, 399–409 (2010).

    Article  CAS  Google Scholar 

  27. Cho, J. K. et al. Captured and cross-linked palladium nanoparticles. J. Am. Chem. Soc. 128, 6276–6277 (2006).

    Article  CAS  Google Scholar 

  28. Horstmann, M. A. et al. Amsacrine combined with etoposide and high-dose methylprednisolone as salvage therapy in acute lymphoblastic leukemia in children. Haematologica 95, 1701–1703 (2005).

    Google Scholar 

  29. Miyaura, N. & Suzuki, A. Palladium-catalyzed cross-coupling reactions of organoboron compounds. Chem. Rev. 95, 2457–2483 (1995).

    Article  CAS  Google Scholar 

  30. Alonso, F., Beletskaya, I. P. & Yus, M. Non-conventional methodologies for transition-metal catalysed carbonecarbon coupling: a critical overview. Part 2: The Suzuki reaction. Tetrahedron 64, 3047–3101 (2008).

    Article  CAS  Google Scholar 

  31. Unciti-Broceta, A., Yusop, M. R., Richardson, P., Walton, J. & Bradley, M. A fluorescein-derived anthocyanidin-inspired pH sensor. Tetrahedron Lett. 50, 3713–3715 (2009).

    Article  CAS  Google Scholar 

  32. Smith, R. A., Porteous, C. M., Gane, A. M. & Murphy, M. P. Delivery of bioactive molecules to mitochondria in vivo. Proc. Natl Acad. Sci. USA 100, 5407–5412 (2003).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported financially by the Government of Malaysia (R.M.Y.), the Swiss National Science Foundation (E.M.V.J.) and the Engineering and Physical Sciences Research Council. R.M.S.M. thanks the Royal Society for a Dorothy Hodgkin Fellowship. The authors thank D. Kelly for his help with the confocal microscopy studies.

Author information

Author notes

  1. Asier Unciti-Broceta

    Present address: Present address: Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XR, UK,

Authors and Affiliations

  1. School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JJ, UK

    Rahimi M. Yusop, Asier Unciti-Broceta, Emma M. V. Johansson, Rosario M. Sánchez-Martín & Mark Bradley

  2. School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM, Bangi, Selangor Darul Ehsan, Malaysia

    Rahimi M. Yusop

Authors
  1. Rahimi M. Yusop
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Asier Unciti-Broceta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emma M. V. Johansson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rosario M. Sánchez-Martín
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mark Bradley
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

R.M.Y. synthesized materials, performed cell-based experiments and analysed the data. A.U.B. designed and supervised the research, analysed the data and co-wrote the paper. E.M.V.J. synthesized materials, performed experiments and analysed the data. R.M.S.M. designed and supervised the experiments and analysed the data. M.B. came up with the concept, designed the research, analysed the data and co-wrote the paper.

Corresponding author

Correspondence to Mark Bradley.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 5424 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yusop, R., Unciti-Broceta, A., Johansson, E. et al. Palladium-mediated intracellular chemistry. Nature Chem 3, 239–243 (2011). https://doi.org/10.1038/nchem.981

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchem.981

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