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Monitoring one-electron photo-oxidation of guanine in DNA crystals using ultrafast infrared spectroscopy

Nature Chemistry volume 7, pages 961967 (2015) | Download Citation


To understand the molecular origins of diseases caused by ultraviolet and visible light, and also to develop photodynamic therapy, it is important to resolve the mechanism of photoinduced DNA damage. Damage to DNA bound to a photosensitizer molecule frequently proceeds by one-electron photo-oxidation of guanine, but the precise dynamics of this process are sensitive to the location and the orientation of the photosensitizer, which are very difficult to define in solution. To overcome this, ultrafast time-resolved infrared (TRIR) spectroscopy was performed on photoexcited ruthenium polypyridyl–DNA crystals, the atomic structure of which was determined by X-ray crystallography. By combining the X-ray and TRIR data we are able to define both the geometry of the reaction site and the rates of individual steps in a reversible photoinduced electron-transfer process. This allows us to propose an individual guanine as the reaction site and, intriguingly, reveals that the dynamics in the crystal state are quite similar to those observed in the solvent medium.

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The work was supported by the Biotechnology and Biological Sciences Research Council grants BB/K019279/1 and BB/M004635/1 (to C.J.C., J.A.B., M.T. and J.P.H.) and a Royal Irish Academy/Royal Society International Exchange Scheme award (to C.J.C., J.M.K. and T.G.), Science Foundation Ireland (SFI) Principle Investigator awards 10/IN.1/B2999 and 13/IA/1865 (to T.G.) and an Irish Research Council PhD Scholarship (to F.E.P.). These experiments were carried out thanks to the programmed access approved by the CLF (Application No. 14230014). The authors gratefully acknowledge the contributions of H. Beer and K. Buchner to the preparation of the metal complex used in this study. The authors also thank the University of Reading for the provision of the Chemical Analysis Facility. S.J.Q. acknowledges financial support from the University College Dublin College of Science. G.W. thanks K. McAuley for the provision of in-house beam time on I03. We thank T. Sorensen (Diamond Light Source), J. Sanchez-Weatherby (Diamond Light Source) and S. Teixeira (Institut Laue-Langevin and University of Keele) for useful discussions.

Author information


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

    • James P. Hall
    • , Páraic M. Keane
    • , Sarah P. Gurung
    • , David J. Cardin
    •  & Christine J. Cardin
  2. Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0QX, UK

    • James P. Hall
    • , Sarah P. Gurung
    •  & Graeme Winter
  3. School of Chemistry, Trinity College, University of Dublin, Dublin 2, Ireland

    • Fergus E. Poynton
    • , Páraic M. Keane
    • , Thorfinnur Gunnlaugsson
    •  & John M. Kelly
  4. Trinity Biomedical Science Institute (TBSI), Trinity College Dublin, Dublin 2, Ireland

    • Fergus E. Poynton
    •  & Thorfinnur Gunnlaugsson
  5. Department of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AD, UK

    • John A. Brazier
  6. Central Laser Facility, Research Complex at Harwell, Science & Technology Facilities Council, Rutherford Appleton Laboratory, Didcot, Oxfordshire OX11 0QX, UK

    • Igor V. Sazanovich
    •  & Michael Towrie
  7. School of Chemistry, University College Dublin, Dublin 4, Ireland

    • Susan J. Quinn


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J.P.H., M.T., C.J.C., J.M.K. and S.J.Q. conceived and designed the experiments; J.P.H., S.P.G., P.M.K., G.W., I.V.S. and S.J.Q. each performed some experiments; J.P.H., F.E.P., P.M.K., G.W., M.T. and S.J.Q. analysed the data; F.E.P., J.A.B., T.G, D.J.C. and C.J.C. contributed the materials; M.T. and I.V.S. contributed the analysis tools; S.J.Q. wrote the paper, with contributions from P.M.K. and major contributions from J.P.H., J.M.K. and C.J.C. All the authors reviewed the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Christine J. Cardin or John M. Kelly or Susan J. Quinn.

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