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A ruthenium(II) polypyridyl complex for direct imaging of DNA structure in living cells

Nature Chemistry volume 1, pages 662–667 (2009)Cite this article

Abstract

In the search for new biological imaging agents, metal coordination compounds able to emit from triplet metal-to-ligand charge transfer (MLCT) states offer many advantages as luminescent probes of DNA structure. However, poor cellular uptake restricts their use in live cells. Here, we present a dinuclear ruthenium(II) polypyridyl system that works as a multifunctional biological imaging agent staining the DNA of eukaryotic and prokaryotic cells for both luminescence and transition electron microscopy. This MLCT ‘light switch’ complex directly images nuclear DNA of living cells without requiring prior membrane permeabilization. Furthermore, inhibition and transmission electron microscopy studies show this to be via a non-endocytotic, but temperature-dependent, mechanism of cellular uptake in MCF-7 cells, and confocal microscopy reveals multiple emission peaks that function as markers for cellular DNA structure.

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Figure 1: The cellular uptake properties of dinuclear Ru(II) tpphz complexes.
Figure 2: Mechanism of cellular uptake of Ru(II) tpphz complex.
Figure 3: Cellular localization of Ru(II) tpphz complex characterized by transition electron microscopy.
Figure 4: A DNA-specific luminescent cellular imaging agent.
Figure 5: Multiple-emission profile as a luminescent probe of DNA structure.

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Acknowledgements

The author thanks C. Hill for TEM assistance and E. Smythe for helpful discussions. This work was supported by the EPSRC (UK) and the White Rose LSI-DTC.

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Authors and Affiliations

  1. Department of Chemistry,

    Martin R. Gill & Jim A. Thomas

  2. Department of Molecular Biology and Biotechnology,

    Jorge Garcia-Lara & Simon J. Foster

  3. Department of Biomedical Science, University of Sheffield, Sheffield, UK

    Martin R. Gill, Carl Smythe & Giuseppe Battaglia

Authors
  1. Martin R. Gill
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  2. Jorge Garcia-Lara
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  4. Carl Smythe
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  5. Giuseppe Battaglia
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Contributions

M.R.G., G.B. and J.A.T. conceived and designed the experiments, M.R.G. and J.G.-L. performed the experiments, all the authors analysed the data, G.B., S.F., C.S. and J.A.T. contributed materials and analysis tools, M.R.G., G.B. and J.A.T. co-wrote the paper.

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Correspondence to Giuseppe Battaglia or Jim A. Thomas.

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Gill, M., Garcia-Lara, J., Foster, S. et al. A ruthenium(II) polypyridyl complex for direct imaging of DNA structure in living cells. Nature Chem 1, 662–667 (2009). https://doi.org/10.1038/nchem.406

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