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Sawhorse-type diruthenium tetracarbonyl complexes containing porphyrin-derived ligands as highly selective photosensitizers for female reproductive cancer cells

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Abstract

Diruthenium tetracarbonyl complexes of the type [Ru2(CO)4(μ2-η2-O2CR)2L2] containing a Ru–Ru backbone with four equatorial carbonyl ligands, two carboxylato bridges, and two axial two-electron ligands in a sawhorse-like geometry have been synthesized with porphyrin-derived substituents in the axial ligands [1: R is CH3, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin], in the bridging carboxylato ligands [2: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is PPh3; 3: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane], or in both positions [4: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin]. Compounds 1–3 were assessed on different types of human cancer cells and normal cells. Their uptake by cells was quantified by fluorescence and checked by fluorescence microscopy. These compounds were taken up by human HeLa cervix and A2780 and Ovcar ovarian carcinoma cells but not by normal cells and other cancer cell lines (A549 pulmonary, Me300 melanoma, PC3 and LnCap prostate, KB head and neck, MDAMB231 and MCF7 breast, or HT29 colon cancer cells). The compounds demonstrated no cytotoxicity in the absence of laser irradiation but exhibited good phototoxicities in HeLa and A2780 cells when exposed to laser light at 652 nm, displaying an LD50 between 1.5 and 6.5 J/cm2 in these two cell lines and more than 15 J/cm2 for the others. Thus, these types of porphyric compound present specificity for cancer cell lines of the female reproductive system and not for normal cells; thus being promising new organometallic photosensitizers.

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Acknowledgments

We thank C. Frochot and S. Hupont (DCPR, ENSIC, Nancy, France) for their assistance in determining the singlet oxygen quantum yields. This work was financially supported by the COST program D39 “Metallo-drug design and action.” We thank the Fondation Suisse pour la Lutte Contre le Cancer (grant no. 227) for financing the purchase of the photodynamic therapy laser and Johnson Matthey Research Centre for a generous loan of ruthenium chloride hydrate. This work is also a part of the research project MSM0021620857 supported by Ministry of Education of the Czech Republic.

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Authors and Affiliations

  1. Institut Universitaire de Pathologie, CHUV, Bugnon 25, 1011, Lausanne, Switzerland

    Frédéric Schmitt & Lucienne Juillerat-Jeanneret

  2. Institut de Chimie, Université de Neuchâtel, Case postale 158, 2009, Neuchâtel, Switzerland

    Mathieu Auzias, Georg Süss-Fink & Bruno Therrien

  3. Department of Inorganic Chemistry, Faculty of Science, Charles University, Hlavova 2030, 12840, Prague 2, Czech Republic

    Petr Štěpnička

  4. Laboratory of Analytical Chemistry, Tokushima Bunri University, Shido, Sanuki, Kagawa, 769-2193, Japan

    Yoshihisa Sei & Kentaro Yamaguchi

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  1. Frédéric Schmitt
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  2. Mathieu Auzias
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  4. Yoshihisa Sei
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  6. Georg Süss-Fink
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  8. Lucienne Juillerat-Jeanneret
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Correspondence to Bruno Therrien or Lucienne Juillerat-Jeanneret.

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Schmitt, F., Auzias, M., Štěpnička, P. et al. Sawhorse-type diruthenium tetracarbonyl complexes containing porphyrin-derived ligands as highly selective photosensitizers for female reproductive cancer cells. J Biol Inorg Chem 14, 693–701 (2009). https://doi.org/10.1007/s00775-009-0482-z

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  • DOI: https://doi.org/10.1007/s00775-009-0482-z

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