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Ruthenium Complexes with Hydrophobic Ligands That Are Key Factors for the Optical Imaging of Physiological Hypoxia

Authors

  • Dr. Hirokazu Komatsu,

    1. Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto 615-8510 (Japan), Fax: (+81) 75-383-2504
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  • Kazuki Yoshihara,

    1. Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto 615-8510 (Japan), Fax: (+81) 75-383-2504
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  • Dr. Hisatsugu Yamada,

    1. Advanced Biomedical Engineering Research Unit, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto 615-8510 (Japan)
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  • Dr. Yu Kimura,

    1. Advanced Biomedical Engineering Research Unit, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto 615-8510 (Japan)
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  • Dr. Aoi Son,

    1. Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto 615-8510 (Japan), Fax: (+81) 75-383-2504
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  • Prof. Dr. Sei-ichi Nishimoto,

    1. Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto 615-8510 (Japan), Fax: (+81) 75-383-2504
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  • Dr. Kazuhito Tanabe

    Corresponding author
    1. Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto 615-8510 (Japan), Fax: (+81) 75-383-2504
    • Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto 615-8510 (Japan), Fax: (+81) 75-383-2504
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Abstract

The phosphorescence emission of ruthenium complexes was applied to the optical imaging of physiological hypoxia. We prepared three complexes with hydrophobic substituents on the phenanthroline ligand and characterized their emission, which was quenched by molecular oxygen. Among the complexes synthesized in this study, a pyrene chromophore-linked ruthenium complex, Ru-Py, exhibited optimal properties for the imaging of hypoxia; the prolonged lifetime of the triplet excited state of the ruthenium chromophore, which was induced by efficient energy distribution and transfer from the pyrene unit, provided the highest sensitivity towards molecular oxygen. The introduction of hydrophobic pyrene increased the lipophilicity of the complex, leading to enhanced cellular uptake. Consequently, the bright phosphorescence of Ru-Py was seen in the cytoplasm of viable hypoxic cells, whereas the signal from aerobic cells was markedly weaker. Thus, we could clearly discriminate between hypoxic and aerobic cells by monitoring the phosphorescence emission. Furthermore, Ru-Py was applied to optical imaging in live mice. An intramuscular injection of Ru-Py successfully visualized ischemia-based hypoxia, which was constructed by leg banding.

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