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Crystal structures of Λ-[Ru(phen)2dppz]2+ with oligonucleotides containing TA/TA and AT/AT steps show two intercalation modes

Nature Chemistry volume 4, pages 621–628 (2012)Cite this article

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Abstract

The ruthenium complex [Ru(phen)2(dppz)]2+ (where phen is phenanthroline and dppz dipyridophenazine is known as a ‘light switch’ complex because its luminescence in solution is significantly enhanced in the presence of DNA. This property is poised to serve in diagnostic and therapeutic applications, but its binding mode with DNA needs to be elucidated further. Here, we describe the crystal structures of the Λ enantiomer bound to two oligonucleotide duplexes. The dppz ligand intercalates symmetrically and perpendicularly from the minor groove of the d(CCGGTACCGG)2 duplex at the central TA/TA step, but not at the central AT/AT step of d(CCGGATCCGG)2. In both structures, however, a second ruthenium complex links the duplexes through the combination of a shallower angled intercalation into the C1C2/G9G10 step at the end of the duplex, and semi-intercalation into the G3G4 step of an adjacent duplex. The TA/TA specificity of the perpendicular intercalation arises from the packing of phenanthroline ligands against the adenosine residue.

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Figure 1: Crystallization of ruthenium cation Λ-[Ru(phen)2(dppz)]2+ and oligonucleotides.
Figure 2: Assembly of duplexes.
Figure 3: Symmetrical perpendicular intercalation geometry at the central TA/TA step.
Figure 4: CC/GG angled intercalation geometry.
Figure 5: Semi-intercalation of one phenanthroline ligand.
Figure 6: Relationship between intercalation geometry (parallel, perpendicular or angled chromophore) and P–P separation across the cavity.

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Acknowledgements

The authors thank G. Doorley (formerly of Trinity College Dublin) for preparing the ruthenium complex, and P. Lincoln (Chalmers University, Gothenburg, Sweden) for reading a draft of the manuscript, very helpful discussions, and making available his unpublished observations. H.N. is funded by a joint ILL/ESRF studentship and the Chemistry Department, University of Reading. J.P.H. is funded by Diamond Light Source and a University of Reading University studentship. The authors acknowledge additional financial support from the Royal Society, the Royal Irish Academy and the Science Foundation Ireland (grant 06/RF/CHP035).

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Authors and Affiliations

  1. Department of Chemistry, University of Reading, Whiteknights, RG6 6AD, Reading, UK

    Hakan Niyazi, James P. Hall & Christine J. Cardin

  2. Diamond Light Source Ltd, Diamond House, Harwell Science and Innovation Campus, Didcot, OX11 0DE, Oxfordshire, UK

    James P. Hall, Graeme Winter & Thomas Sorensen

  3. School of Chemistry, Trinity College, Dublin, 2, Ireland

    Kyra O'Sullivan & John M. Kelly

  4. Institut Laue-Langevin, 6 Rue Jules Horowitz, Grenoble, 38042, France

    Hakan Niyazi

  5. European Synchrotron Radiation Facility, 6 Rue Jules Horowitz, Grenoble, 38043, France

    Hakan Niyazi

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Contributions

C.J.C., J.P.H. and J.M.K. conceived and designed the experiments. H.N., J.P.H., K.O'S. and C.J.C. performed the experiments. G.W. and T.S. contributed analytical tools. J.P.H., H.N. and C.J.C. analysed the data. C.J.C. wrote the paper, with contributions from J.M.K., J.P.H. and H.N. All authors discussed the results and commented on the manuscript. H.N. and J.P.H. contributed equally to this work.

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Correspondence to Christine J. Cardin.

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Niyazi, H., Hall, J., O'Sullivan, K. et al. Crystal structures of Λ-[Ru(phen)2dppz]2+ with oligonucleotides containing TA/TA and AT/AT steps show two intercalation modes. Nature Chem 4, 621–628 (2012). https://doi.org/10.1038/nchem.1397

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