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  • Publication
    Accès libre
    Combined arene ruthenium porphyrins as chemotherapeutics and photosensitizers for cancer therapy
    (2009)
    Schmitt, Frédéric
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    Govindaswamy, Padavattan
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    Zava, Olivier
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    Juillerat-Jeanneret, Lucienne
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    Mononuclear 5-(4-pyridyl)-10,15,20-triphenylporphyrin and 5-(3-pyridyl)-10,15,20-triphenylporphyrin as well as tetranuclear 5,10,15,20-tetra(4-pyridyl)porphyrin (tetra-4-pp) and 5,10,15,20-tetra(3-pyridyl)porphyrin) (tetra-3-pp) arene ruthenium(II) derivatives (arene is C6H5Me or p-PriC6H4Me) were prepared and evaluated as potential dual photosensitizers and chemotherapeutics in human Me300 melanoma cells. In the absence of light, all tetranuclear complexes were cytotoxic (IC50 ≤ 20 μM), while the mononuclear derivatives were not (IC50 ≥ 100 μM). Kinetic studies of tritiated thymidine and tritiated leucine incorporations in cells exposed to a low concentration (5 μM) of tetranuclear p-cymene derivatives demonstrated a rapid inhibition of DNA synthesis, while protein synthesis was inhibited only later, suggesting arene ruthenium–DNA interactions as the initial cytotoxic process. All complexes exhibited phototoxicities toward melanoma cells when exposed to laser light of 652 nm. At low concentration (5 μM), LD50 of the mononuclear derivatives was between 5 and 10 J/cm2, while for the tetranuclear derivatives LD50 was approximately 2.5 J/cm2 for the [Ru46-arene)4 (tetra-4-pp)Cl8] complexes and less than 0.5 J/cm2 for the [Ru46-arene)4 (tetra-3-pp)Cl8] complexes. Examination of cells under a fluorescence microscope revealed the [Ru46-arene)4 (tetra-4-pp)Cl8] complexes as cytoplasmic aggregates, whereas the [Ru4(η6-arene)4(tetra-3-pp)Cl8] complexes were homogenously dispersed in the cytoplasm. Thus, these complexes present a dual synergistic effect with good properties of both the arene ruthenium chemotherapeutics and the porphyrin photosensitizer.
  • Publication
    Accès libre
    Synthesis, Molecular Structure, and Anticancer Activity of Cationic Arene Ruthenium Metallarectangles
    (2009)
    Mattsson, Johan
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    Govindaswamy, Padavattan
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    Renfrew, Anna K.
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    Dyson, Paul J.
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    Štěpnička, Petr
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    The cytotoxicities of a new series of cationic metallarectangles have been established in the A2780 ovarian cancer cell line. Interestingly, the large rectangles incorporating 1,2-bis(4-pyridyl)ethylene linkers are ca. 5 times more cytotoxic (IC50 ≤ 6 μM) than the 4,4-bipyridine analogues (IC50 ≥ 30 μM), thus suggesting a correlation between cytotoxicity and the size of the rectangle.
  • Publication
    Métadonnées seulement
    Synthesis, Molecular Structure, and Anticancer Activity of Cationic Arene Ruthenium Metallarectangles
    (2009)
    Mattsson, Johan
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    Govindaswamy, Padavattan
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    Renfrew, Anna K.
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    Dyson, Paul J.
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    Stepnicka, Petr
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    Cationic arene ruthenium-based tetranuclear complexes comprising rectangular structures have been obtained from the dinuclear arene ruthenium complexes [Ru2(arene)2(OO?OO)2Cl2] (arene = p-cymene, hexamethylbenzene; OO?OO = 2,5-dihydroxy-1,4-benzoquinonato, 2,5-dichloro-1,4-benzoquinonato) by reaction with pyrazine or bipyridine linkers (N?N = pyrazine, 4,4'-bipyridine, 1,2-bis(4-pyridyl)ethylene) in methanol in the presence of AgO3SCF3, forming tetranuclear cations of general formula [Ru4(arene)4(N?N)2(OO?OO)2]4+. All complexes were isolated in good yield as triflate salts and were characterized by NMR and IR spectroscopy and studied by cyclic voltammetry. The cytotoxicities of the water-sol. compds. of the 4,4'-bipyridine and 1,2-bis(4-pyridyl)ethylene series have been established using ovarian A2780 cancer cells. The large rectangles incorporating 1,2-bis(4-pyridyl)ethylene linkers are ca. 5 times more cytotoxic (IC50 ? 6 ?M) than the 4,4'-bipyridine-contg. cations (IC50 ? 30 ?M). Structural characterization by x-ray diffraction of two representative compds., i.e., the triflate salts of [Ru4(hexamethylbenzene)4(4,4'-bipyridine)2(2,5-dihydroxy-1,4-benzoquinonato)2]4+and [Ru4(hexamethylbenzene)4(1,2-bis(4-pyridyl)ethylene)2(2,5-dichloro-1,4-benzoquinonato)2]4+, reveals differently sized cavities, different flexibilities, and different packing arrangements, suggesting a correlation between these structural properties and the obsd. cytotoxicities. [on SciFinder(R)]
  • Publication
    Accès libre
    Encapsulation of Triphenylene Derivatives in the Hexanuclear Arene Ruthenium Metallo-Prismatic Cage [Ru6 (p-PriC6H4Me)6(tpt)2 (dhbq)3]6+ (tpt = 2,4,6-tri(pyridin-4-yl)-1,3,5-triazine, dhbq = 2,5-dihydroxy-1,4-benzoquinonato)
    (2008)
    Govindaswamy, Padavattan
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    Furrer, Julien
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    A large cationic triangular metallo-prism, [Ru6(p-PriC6H4Me)6 (tpt)2 (dhbq)3]6+ (1)6+, incorporating p-cymene ruthenium building blocks, bridged by 2,5-dihydroxy-1,4-benzoquinonato (dhbq) ligands, and connected by two 2,4,6-tri(pyridin-4-yl)-1,3,5-triazine (tpt) subunits, allows the permanent encapsulation of the triphenylene derivatives hexahydroxytriphenylene, C18H6 (OH)6 and hexamethoxytriphenylene, C18H6 (OMe)6. These two cationic carceplex systems [C18H6 (OH)61]6+ and [C18H6 (OMe)61]6+ have been isolated as their triflate salts. The molecular structure of these systems has been established by one-dimensional 1H ROESY NMR experiments as well as by the single-crystal structure analysis of [C18H6 (OMe)61][O3SCF3]6.
  • Publication
    Métadonnées seulement
    Encapsulation of triphenylene derivatives in the hexanuclear arene ruthenium metallo-prismatic cage [Ru6(p-PriC6H4Me)6(tpt)2(dhbq)3]6+ (tpt = 2,4,6-tri(pyridin-4-yl)-1,3,5-triazine, dhbq = 2,5-dihydroxy-1,4-benzoquinonato)
    (2008)
    Govindaswamy, Padavattan
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    Furrer, Julien
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    ;
    A large cationic triangular metallo-prism, [Ru6(p-PriC6H4Me)6(tpt)2(dhbq)3]6+ (1)6+, incorporating p-cymene ruthenium building blocks, bridged by 2,5-dihydroxy-1,4-benzoquinonato (dhbq) ligands, and connected by two 2,4,6-tri(pyridin-4-yl)-1,3,5-triazine (tpt) subunits, allows the permanent encapsulation of the triphenylene derivs. hexahydroxytriphenylene, C18H6(OH)6 and hexamethoxytriphenylene, C18H6(OMe)6. These two cationic carceplex systems [C18H6(OH)6?1]6+ and [C18H6(OMe)6?1]6+ were isolated as their triflate salts. The mol. structure of these systems was established by 1-dimensional 1H ROESY NMR expts. as well as by the single-crystal structure anal. of [C18H6(OMe)6?1][O3SCF3]6. [on SciFinder(R)]
  • Publication
    Métadonnées seulement
    The "complex-in-a-complex" cations [(acac)2M?Ru6-(p-iPrC6H4Me)6(tpt)2(dhbq)3]6+: a trojan horse for cancer cells
    (2008) ; ;
    Govindaswamy, Padavattan
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    Renfrew, Anna K.
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    Dyson, Paul J.
    The cytotoxicities of the large cationic arene-ruthenium prismatic cage [Ru6(p-iPrC6H4Me)6(tpt)2(dhbq)3]6+ (tpt = 2,4,6-tris(pyridin-4-yl)-1,3,5-triazine, dhbq = 2,5-dihydroxy-1,4-benzoquinolato; 16+), and its "complex-in-a-complex" derivs. [(acac)2M-1]6+ (M = Pd, Pt; acac = acetylacetonate), are evaluated in comparison with free [M(acac)2]. The differences in cytotoxicity suggest that, like a "Trojan Horse", leaching of the guest from the cage once inside a cell accelerates and increases the cytotoxic effect. [on SciFinder(R)]
  • Publication
    Métadonnées seulement
    Ruthenium Porphyrin Compounds for Photodynamic Therapy of Cancer
    (2008)
    Schmitt, Frederic
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    Govindaswamy, Padavattan
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    Ang, Wee Han
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    Dyson, Paul J.
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    Juillerat-Jeanneret, Lucienne
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    Five 5,10,15,20-tetra(4-pyridyl)porphyrin (TPP) areneruthenium(II) derivs., a p-cymeneosmium, a pentamethylcyclopentadienyliridium and a pentamethylcyclopentadienylrhodium analog were prepd. and characterized as potential photosensitizing chemotherapeutic agents. The dinuclear areneruthenium complexes [Ru(?6-arene)(?-Cl)Cl]2 (arene = C6H6, C6H5CH3, p-iPrC6H4Me, C6Me6, and 1,4-C6H4(COOEt)2) react with TPP in MeOH to give the corresponding tetranuclear complexes [Ru4(?6-arene)4(TPP)Cl8] (arene = C6H6 (1, 56% yield), C6H5CH3 (2, 70%), p-iPrC6H4Me (3, 70%), C6Me6 (4, 79%), 1,4-C6H4(COOEt)2 (5, 73%)). The dinuclear p-cymeneosmium complex [Os(?6-p-iPrC6H4Me)(?-Cl)Cl]2 reacts with TPP to form the tetranuclear areneosmium complex [Os4(?6-p-iPrC6H4Me)4(TPP)Cl8] (6) in 47% yield. The isoelectronic Rh and Ir pentamethylcyclopentadienyl derivs. [Rh4(?5-C3Me5)4(TPP)Cl8] (7, 73%) and [Ir4(?5-C3Me5)4(TPP)Cl8] (8, 83%) were obtained in MeOH from the reaction of [M(?5-C5Me5)(?-Cl)Cl]2 (M = Rh, Ir) with TPP. The mol. structures of 4 and 7 were detd. by x-ray crystallog. The biol. effects of all these derivs. were assessed on human melanoma tumor cells, and their cellular uptake and intracellular localization were detd. All mols., except the Rh complex which was not cytotoxic, demonstrated comparable cytotoxicity in the absence of laser irradn. The Ru complexes exhibited excellent phototoxicities toward melanoma cells when exposed to laser light at 652 nm. Cellular uptake and localization microscopy studies of [Ru4(?6-C6H5CH3)4(TPP)Cl8] and [Rh4(?5-C5Me5)4(TPP)Cl8] revealed that they accumulated in the melanoma cell cytoplasm in granular structures different from lysosomes. The fluorescent porphyrin moiety and the metal component were localized in similar structures within the cells. Thus, the porphyrin areneruthenium(II) derivs. represent a promising new class of organometallic photosensitizers able to combine chemotherapeutic activity with photodynamic therapeutic treatment of cancer. [on SciFinder(R)]
  • Publication
    Métadonnées seulement
    Encapsulation of Aromatic Molecules in Hexanuclear Arene Ruthenium Cages: A Strategy to Build Up Organometallic Carceplex Prisms with a Dangling Arm Standing Out
    (2008)
    Mattsson, Johan
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    Govindaswamy, Padavattan
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    Furrer, Julien
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    Sei, Yoshihisa
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    Yamaguchi, Kentaro
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    Self-assembly of 2,4,6-tris(pyridin-4-yl)-1,3,5-triazine (tpt) subunits with p-cymene (p-PriC6H4Me) or hexamethylbenzene (C6Me6) Ru building blocks and 2,5-dihydroxy-1,4-benzoquinonato (dhbq) or 2,5-dihchloro-3,6-dihydroxy-1,4-benzoquinonato (dchq) bridges affords the triangular prismatic organometallic cations [Ru6(p-PriC6H4Me)6(tpt)2(dhbq)3]6+ ([1]6+), [Ru6(p-PriC6H4Me)6(tpt)2(dchq)3]6+ ([2]6+), [Ru6(C6Me6)6(tpt)2(dhbq)3]6+ ([3]6+), and [Ru6(C6Me6)6(tpt)2(dchq)3]6+ ([4]6+). These hexanuclear cationic cages are isolated in good yield as their triflate salts. The assembly of 1-4 can also be achieved in the presence of large arom. mols. such as pyrene, fluoranthene, benzo[e]pyrene, triphenylene, or coronene to give the corresponding inclusion systems [arom.?1]6+, [arom.?2]6+, [arom.?3]6+, and [arom.?4]6+. The closed proximity of the encapsulated mol. with the different components of the cage and the carceplex nature of these systems are confirmed by 1-dimensional ROESY 1H NMR expts., mass spectrometry, and the single-crystal structure anal. of [pyrene?1][O3SCF3]6 and [benzo[e]pyrene?1][O3SCF3]6. Pyrene can be encapsulated even if it contains a functionalized aliph. substituent; in this case the arom. moiety is included in the cage, while the functionalized side arm stands out. Thus, Me 4-(pyren-1-yl)butanoate (pyrene-R) is encapsulated in 1 to give the carceplex [pyrene-R?1]6+, in which the Me butyrate arm dangles outside the cage while the pyrene moiety is firmly trapped by the metallo-prismatic cation, as demonstrated by 1H NMR expts. and ESI-MS. [on SciFinder(R)]
  • Publication
    Accès libre
  • Publication
    Accès libre
    Organometallic boxes built from 5,10,15,20-tetra(4-pyridyl)porphyrin panels and hydroxyquinonato-bridged diruthenium clips
    (2008)
    Barry, Nicolas P.E.
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    Govindaswamy, Padavattan
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    Furrer, Julien
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    Self-assembly of 5,10,15,20-tetra(4-pyridyl)porphyrin (tpp-H2) tetradentate panels with dinuclear arene ruthenium clips [Ru26-arene)2 (dhbq)Cl2] (arene = C6H5Me, p-PriC6H4Me, C6Me6; dhbq = 2,5-dihydroxy-1,4-benzoquinonato) affords the cationic organometallic boxes [Ru86-C6H5Me)8 (tpp-H2)2 (dhbq)4]8+ ([1]8+), [Ru86-p-PriC6H4Me)8 (tpp-H2)2(dhbq)4]8+ ([2]8+) and [Ru86-C6Me6)8 (tpp-H2)2 (dhbq)4]8+ ([3]8+). These octanuclear cations have been isolated as their triflate salts and characterised by mass spectrometry, NMR and IR spectroscopy. The molecular structure of these systems was deduced by one-dimensional and two-dimensional NMR experiments (ROESY, COSY, HSQC).