Résultat de la recherche
Organometallic Cages as Vehicles for Intracellular Release of Photosensitizers
Water-soluble metalla-cages were used to deliver hydrophobic porphin molecules to cancer cells. After internalization, the photosensitizer was photoactivated, significantly increasing the cytotoxicity in cells. During the transport, the photosensitizer remains nonreactive to light, offering a new strategy to tackle overall photosensitization, a limitation often encountered in photodynamic therapy.
Excellent Correlation between Drug Release and Portal Size in Metalla-Cage Drug-Delivery Systems
A series of large cationic hexanuclear metalla-prisms, [Ru6(p-iPrC6H4Me)6(tpt)2(donq)3]6+, [Ru6(p-iPrC6H4Me)6(tpt)2(doaq)3]6+ and [Ru6(p-iPrC6H4Me)6(tpt)2(dotq)3]6+, composed of p-cymene–ruthenium building blocks bridged by OO∩OO ligands (donq=5,8-dioxido-1,4-naphthoquinonato; doaq=5,8-dioxido-1,4-anthraquinonato, dotq=6,11-dioxido-5,12-naphthacenedionato) and connected by two 2,4,6-tripyridin-4-yl-1,3,5-triazine (tpt) panels, which encapsulate the guest molecules 1-(4,6-dichloro-1,3,5-triazin-2-yl)pyrene and Pd(acac)2, have been prepared. The host–guest properties of these water-soluble delivery systems were studied in solution by NMR and fluorescence spectroscopy, providing the stability constants (K) for these host–guest systems. Moreover, the ability of the hosts to deliver the guests into cancer cells was evaluated and the uptake mechanism studied; the rate of release of the guest molecule was found to depend on the portal size of the host.
Permanent Encapsulation or Host–Guest Behavior of Aromatic Molecules in Hexanuclear Arene Ruthenium Prisms
Cationic arene ruthenium metallaprisms of the general formula [Ru6(p-cymene)6(tpt)2(OO∩OO)3]6+ {tpt = 2,4,6-tris(4-pyridyl)-1,3,5-triazine; OO∩OO = 9,10-dioxo-9,10-dihydroanthracene-1,4-diolato [1]6+, 6,11-dioxo-6,11-dihydronaphthacene-5,12-diolato [2]6+} have been obtained from the corresponding dinuclear arene ruthenium complexes [Ru2(p-cymene)2(OO∩OO)Cl2] by reaction with tpt and silver trifluoromethanesulfonate. Aromatic molecules (phenanthrene, pyrene, triphenylene, coronene) present during the synthesis of these metallaprisms are permanently encapsulated to give carceplex systems. All empty cages ([1]6+ and [2]6+) and carceplex systems ([guest⊂1]6+ and [guest⊂2]6+) were isolated in good yield as trifluoromethanesulfonate salts and characterized by NMR, UV, and IR spectroscopy. The host–guest properties of [1]6+ and [2]6+ were studied in solution in the presence of small aromatic molecules (phenanthrene andpyrene). The stability constant of association (Ka) wasestimated by NMR spectroscopy for the following host–guest systems: [phenanthrene⊂1]6+, [pyrene⊂1]6+ and [phenanthrene⊂2]6+, [pyrene⊂2]6+. All Ka values were found to be larger than 2.0 × 104M–1 for these host–guest systems ([D3]acetonitrile, 21 °C).
Photochemical [2+2] cycloaddition of the olefinic double bonds in the supramolecular rectangle [Ru4(η6-p-cymene)4(μ-oxalato)2(μ-4,4′-bipyridylethylene)2]4+
Self-assembly of 4,4′-bipyridylethylene (bpe) bidentate connector with the dinuclear arene ruthenium clip [Ru2(η6-p-cymene)2(μ-oxalato)Cl2] in the presence of silver triflate affords the cationic organometallic rectangle [Ru4(η6-p-cymene)4(μ-oxalato)2(μ-bpe)2]4+ ([1][CF3SO3]4). Upon UV irradiation of a methanol solution of [1]4+, dimerisation of the olefinic double bonds of the two parallel bpe ligands occurs, thus giving rise to the [2+2] cycloaddition derivative [Ru4(η6-p-cymene)4(μ-oxalato)2(μ-tpcb)]4+ ([2][CF3SO3]4) (tpcb = tetrakis(4-pyridyl)cyclobutane). The [2+2] photodimerisation reaction was followed by 1H NMR spectroscopy. Moreover, the molecular structure of these two systems was deduced by one-dimensional and two-dimensional NMR experiments (1H, 13C, ROESY, COSY, HSQC). These data suggest the formation of only the rctt-tetrakis(4-pyridyl)cyclobutane isomer.
Anticancer activity of tetracationic arene ruthenium metalla-cycles
A series of cationic metalla-cycles of the general formulae [(η6-p-cym)4Ru4(OO∩OO)2(N∩N)2]4+ and [(η6-p-cym)4Ru4(NO∩NO)2(N∩N)2]4+ has been prepared from the dinuclear arene ruthenium precursors [(η6-p-cym)2Ru2(OO∩OO)2Cl2] (OO∩OO = oxalato, 1,4-benzoquinonato-2,5-diolato, 1,4-naphtoquinonato-5,8-diolato, 9,10-anthraquinonato-1,4-diolato, 5,12-tetraquinonato-6,11-diolato) and [(η6-p-cym)2Ru2(NO∩NO)2Cl2] (NO∩NO = oxamido, oxonico) by reaction with two different bidentate linkers (N∩N = 1,2-bis(4-pyridyl)ethylene, 1,2-bis(4-pyridyl)ethane) in the presence of silver triflate. All complexes were isolated as triflate salts and characterised by NMR, infrared, UV-visible, mass spectrometry and by elemental analysis. The cytotoxicities of the tetranuclear ruthenium complexes have been established using ovarian A2780 and A2780cisR cancer cell lines. All complexes exhibit moderate to excellent activity on both the cisplatin resistant and cisplatin sensitive cells, thus suggesting a mode of action different from cisplatin.
Anticancer activity of osmium metalla-rectangles
A series of cationic metalla-rectangles of the general formula [(p-cymene)4Os4(OO∩OO)2(N∩N)2]4+ have been obtained in methanol from the dinuclear arene osmium precursors [(p-cymene)2Os2 (OO∩OO)2Cl2] (OO∩OO = 2,5-dioxydo-1,4-benzoquinonato (dhbq), 2,5-dichloro-1,4-benzoquinonato (dcbq)) by reaction with bipyridine linkers (N∩N = 4,4′-bipyridine, 1,2-bis(4-pyridyl)ethylene) in the presence of AgCF3SO3. All complexes were isolated as triflate salts and characterised by NMR, IR and UV-visible spectroscopy. The cytotoxicities of the dinuclear and tetranuclear osmium complexes were established using ovarian A2780 cancer cell lines. The most active metalla-rectangle, [(p-cymene)4Os4(dhbq)2(4,4′-bipyridine)2]4+, shows an IC50 value of 5.7 μM (comparable to cisplatin) against A2780 cancer cells and 7.5 μM against the cisplatin resistant A2780cisR cells.
Highly Efficient NMR Enantiodiscrimination of Chiral Octanuclear Metalla-Boxes in Polar Solvent
Detection of the molecular chirality of a series of octanuclear metalla-boxes can be readily achieved using the NMR chiral solvating agent Λ-BINPHAT in CD3CN: only 0.05 to 0.10 equiv being necessary for a complete baseline separation of some of the proton signals.
Ru2(CO)4(OOCR)2L2 sawhorse-type complexes containing axial 5-(4-pyridyl)-10,15,20-triphenylporphyrin ligands
The thermal reaction of Ru3(CO)12 with various carboxylic acids (benzoic, 4-hydroxyphenylacetic, ferrocenic, stearic, oleic, 4-(octadecyloxy)benzoic) in refluxing tetrahydrofuran, followed by addition of 5-(4-pyridyl)-10,15,20-triphenylporphyrin (L), gives the dinuclear complexes Ru2(CO)4(OOCR)2L2 (1: R = –C6H5, 2: R = –CH2-p-C6H4OH, 3: R = –C5H4FeC5H5, 4: R = –(CH2)16CH3, 5: R = –(CH2)7CHdouble bond; length as m-dashCH(CH2)7CH3, 6: R = –p-C6H4O(CH2)17CH3). Complexes 1–6 were characterised by IR, NMR, and ESI-MS as well as by elemental analysis. The UV–Vis spectra show the Soret band centred at 417 nm and the Q bands at 515, 550, 590 and 645 nm, respectively.
In- and Out-of-Cavity Interactions by Modulating the Size of Ruthenium Metallarectangles
Cationic (arene)ruthenium-based tetranuclear complexes of the general formula [Ru4(η6-p-cymene)4(μ-N∩N)2(μ-OO∩OO)2]4+ were obtained from the dinuclear (arene)ruthenium complexes [Ru2 (η6-p-cymene)2(μ-OO∩OO)2Cl2] (p-cymene=1-methyl-4-(1-methylethyl)benzene, OO∩OO=5,8-dihydroxy-1,4-naphthoquinonato(2−), 9,10-dihydroxy-1,4-anthraquinonato(2−), or 6,11-dihydroxynaphthacene-5,12-dionato(2−)) by reaction with pyrazine or bipyridine linkers (N∩N=pyrazine, 4,4′-bipyridine, 4,4′-[(1E)-ethene-1,2-diyl]bis[pyridine]) in the presence of silver trifluoromethanesulfonate (CF3SO3Ag) (Scheme). All complexes 4–12 were isolated in good yield as CF3SO3- salts, and characterized by NMR and IR spectroscopy. The host–guest properties of the metallarectangles incorporating 4,4′-bipyridine and (4,4′-[(1E)-ethene-1,2-diyl]bis[pyridine] linkers were studied in solution by means of multiple NMR experiments (1D, ROESY, and DOSY). The largest metallarectangles 10–12 incorporating (4,4′-[(1E)-ethene-1,2-diyl]bis[pyridine] linkers are able to host an anthracene, pyrene, perylene, or coronene molecule in their cavity, while the medium-size metallarectangles 7–9 incorporating 4,4′-bipyridine linkers are only able to encapsulate anthracene. However, out-of-cavity interactions are observed between these 4,4′-bipyridine-containing rectangles and pyrene, perylene, or coronene. In contrast, the small pyrazine-containing metallarectangles 4–6 show no interaction in solution with this series of planar aromatic molecules.
Host-Guest Chemistry in the Hexanuclear (Arene)ruthenium Metalla-Prismatic Cage [Ru6(p-cymene)6(tpt)2(dhnq)3]6+
A large cationic triangular metalla-prism, [Ru6(p-cymene)6(tpt)2(dhnq)3]6+ ([1]6+), incorporating (p-cymene)ruthenium building blocks, bridged by 5,8-dihydroxy-1,4-naphthoquinonato (dhnq) ligands, and connected by two 2,4,6-tri(pyridin-4-yl)-1,3,5-triazine (tpt) subunits, allows encapsulation of various guest molecules. This cationic cage, isolated as its triflate salt, possesses a portal size smaller than its cavity, thus allowing both, permanent and temporary encapsulation of guest molecules. The host-guest properties of [1]6+ have been studied in solution in the presence of planar molecules [phenanthrene, pyrene, (pyren-1-ylmethyl)amine, Pt(acac)2, triphenylene]. The stability constant of association (Ka) was estimated by NMR spectroscopy for the following host-guest systems: [pyrene1]6+, [phenanthrene1]6+ and [(pyren-1-ylmethyl)amine1]6+. All Ka values were found to be larger than 2.4 × 104 M-1 for these host-guest systems ([D3]acetonitrile, 21 °C). The other two synthesised complexes, [Pt(acac)21]6+ and [triphenylene1]6+, were shown to act as carceplexes only.A large cationic triangular metalla-prism, [Ru6(p-cymene)6(tpt)2(dhnq)3]6+ ([1]6+), incorporating (p-cymene)ruthenium building blocks, bridged by 5,8-dihydroxy-1,4-naphthoquinonato (dhnq) ligands, and connected by two 2,4,6-tri(pyridin-4-yl)-1,3,5-triazine (tpt) subunits, allows encapsulation of various guest molecules. This cationic cage, isolated as its triflate salt, possesses a portal size smaller than its cavity, thus allowing both, permanent and temporary encapsulation of guest molecules. The host-guest properties of [1]6+ have been studied in solution in the presence of planar molecules [phenanthrene, pyrene, (pyren-1-ylmethyl)amine, Pt(acac)2, triphenylene]. The stability constant of association (Ka) was estimated by NMR spectroscopy for the following host-guest systems: [pyrene1]6+, [phenanthrene1]6+ and [(pyren-1-ylmethyl)amine1]6+. All Ka values were found to be larger than 2.4 × 104 M-1 for these host-guest systems ([D3]acetonitrile, 21 °C). The other two synthesised complexes, [Pt(acac)21]6+ and [triphenylene1]6+, were shown to act as carceplexes only.