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ABSTRACT: Following our strategy of coupling cyclin-dependent kinase (Cdk) inhibitors with organometallic moieties to improve their physicochemical properties and bioavailability, five organoruthenium complexes (1c-5c) of the general formula [RuCl(η(6)-arene)(L)]Cl have been synthesized in which the arene is 4-formylphenoxyacetyl-η(6)-benzylamide and L is a Cdk inhibitor [3-(1H-benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines (L1-L3) and indolo[3,2-d]benzazepines (L4 and L5)]. All of the compounds were characterized by spectroscopic and analytical methods. Upon prolonged standing (2-3 months) at room temperature, the dimethyl sulfoxide (DMSO) solutions of 1c and 2c(-HCl) afforded residues, which after recrystallization from EtOH and EtOH/H(2)O, respectively, were shown by X-ray diffraction to be cis,cis-[Ru(II)Cl(2)(DMSO)(2)(L1)]·H(2)O and mer-[Ru(II)Cl(DMSO)(3)(L2-H)]·H(2)O. Compound 5c, with a coordinated amidine unit, undergoes E/Z isomerization in solution. The antiproliferative activities and effects on the cell cycle of the new compounds were evaluated. Complexes 1c-5c are moderately cytotoxic to cancer cells (CH1, SW480, A549, A2780, and A2780cisR cell lines). Therefore, in order to improve their antiproliferative effects, as well as their drug targeting and delivery to cancer cells, 1c-5c were conjugated to recombinant human serum albumin, potentially exploiting the so-called "enhanced permeability and retention" effect that results in the accumulation of macromolecules in tumors. Notably, a marked increase in cytotoxicity of the albumin conjugates was observed in all cases.
Inorganic Chemistry 11/2011; 50(24):12669-79. · 4.60 Impact Factor
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ABSTRACT: A series of cationic metalla-cycles of the general formulae [(η(6)-p-cym)(4)Ru(4)(OO∩OO)(2)(N∩N)(2)](4+) and [(η(6)-p-cym)(4)Ru(4)(NO∩NO)(2)(N∩N)(2)](4+) has been prepared from the dinuclear arene ruthenium precursors [(η(6)-p-cym)(2)Ru(2)(OO∩OO)(2)Cl(2)] (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 [(η(6)-p-cym)(2)Ru(2)(NO∩NO)(2)Cl(2)] (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.
Dalton Transactions 06/2011; 40(27):7172-80. · 3.84 Impact Factor
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ABSTRACT: The combination of platinum nanoparticles with a tripodal osmium complex that anchors to the metal surface leads, under visible light irradiation, to the formation of solvated electrons. The formation kinetics is limited by the detachment of the electron from the platinum surface into the solution, the particle showing a type of capacitor behavior.Keywords: photochemistry; photophysics; solvated electrons; photocatalysis; fast spectroscopy
05/2011;
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ABSTRACT: Luminescent Os(II) and Ir(III) complexes containing a tripodal-type structure terminalized
with three thiol derivatives are described. The tripod is introduced through derivatization,
with a rigid spacer, of a phenanthroline ligand coordinated to the metal ion, and the
entire structure possesses axial geometry. The geometry of the complexes combined with the
three anchoring sites, the thiol groups, allows the complexes to adopt an almost perpendicular
arrangement to the surfaces and the formation of a well-packed monolayer on Au substrates.
The photophysical and electrochemical behavior of the complexes is studied in solution
and on surfaces. Furthermore, a self-assembled monolayer (SAM) of Os(II) complexes
on an ultraflat Au surface is used to fabricate a metal–molecule–metal junction with Au and
In Ga eutectic as electrodes. The Os(II) SAM in the tunneling junction exhibits rectification
behavior which is opposite in direction to that which we have previously shown for Ru(II)
SAMs.
Pure Appl. Chem. 03/2011; Vol. 83(4):779–799.
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ABSTRACT: Two luminescent ruthenium complexes containing tripod-type end groups linked through a rigid spacer to a phenanthroline derivative, able to confer an axial geometry to the complexes, are described. One of the compounds is functionalized with thioacetate groups in order to link the metal complex to metallic surfaces. The photophysical and electrochemical behavior of the complexes are studied in solution and on conductive substrates and, furthermore, self-assembled monolayers are investigated in a junction using gold and an indium gallium eutectic, as electrodes, and by time-resolved confocal microscopy. The results show that the complexes form very stable and well-ordered monolayers because of the tripod system, which can anchor the complex almost perpendicular to the surfaces.
Inorganic Chemistry 12/2010; 50(5):1581-91. · 4.60 Impact Factor
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Frédéric Pelletier,
Virginie Comte,
Alexandre Massard,
Margot Wenzel,
Stéphanie Toulot,
Philippe Richard,
Michel Picquet,
Pierre Le Gendre,
Olivier Zava, Fabio Edafe,
Angela Casini,
Paul J Dyson
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ABSTRACT: A series of bimetallic titanium-ruthenium complexes of general formula [(η(5)-C(5)H(5))(μ-η(5):κ(1)-C(5)H(4)(CR(2))(n)PR'R'')TiCl(2)](η(6)-p-cymene)RuCl(2) (n = 0, 1, 2 or 4; R = H or Me; R' = H, Ph, or Cy; R'' = Ph or Cy) have been synthesized, including two novel compounds as well as two cationic derivatives of formula [(η(5)-C(5)H(5))(μ-η(5):κ(1)-C(5)H(4)(CH(2))(n)PPh(2))TiCl(2)] [(η(6)-p-cymene)RuCl](BF(4)) (n = 0 or 2). The solid state structure of two of these compounds was also established by X-ray crystallography. The complexes showed a cytotoxic effect on human ovarian cancer cells and were markedly more active than their Ti or Ru monometallic analogues titanocene dichloride and RAPTA-C, respectively. Studies of cathepsin B inhibition, an enzyme involved in cancer progression, showed that enzyme inhibition by the bimetallic complexes is influenced by the length of the alkyl chain in between the metal centers. Complementary ESI-MS studies provided evidence for binding of a Ru(II) fragment to proteins.
Journal of Medicinal Chemistry 10/2010; 53(19):6923-33. · 4.80 Impact Factor
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ABSTRACT: A series of organometallic compounds of general formula [(arene)M(PTA)(n)X(m)]Y (arene = eta(6)-C(10)H(14), eta-C(5)Me(5)); M = Ru(ii), Os(ii), Rh(iii) and Ir(iii); X = Cl, mPTA; Y = OTf, PF(6)) have been screened for their cytotoxicity and ability to inhibit cathepsin B in vitro, in comparison to the antimetastatic compound NAMI-A. The Ru and Os analogues and NAMI-A showed similar enzyme inhibition properties (with IC(50) values in the low muM range), whereas the Rh(iii) and Ir(iii) compounds were inactive. In order to build up a rational for the observed differences, DFT calculations of the metal complexes adducts with N-acetyl-l-cysteine-N'-methylamide, a mimic for the Cys residue in the cathepsin B active site, were performed to provide insights into binding thermodynamics in solution. Initial structure-activity relationships have been defined with the calculated binding energies of the M-S bonds correlating well with the observed inhibition properties of the compounds.
Dalton Transactions 06/2010; 39(23):5556-63. · 3.84 Impact Factor
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ABSTRACT: A series of cationic metalla-rectangles of the general formula [(p-cymene)(4)Os(4)(OO[intersection]OO)(2)(N[intersection]N)(2)](4+) have been obtained in methanol from the dinuclear arene osmium precursors [(p-cymene)(2)Os(2)(OO[intersection]OO)(2)Cl(2)] (OO[intersection]OO = 2,5-dioxydo-1,4-benzoquinonato (dhbq), 2,5-dichloro-1,4-benzoquinonato (dcbq)) by reaction with bipyridine linkers (N[intersection]N = 4,4'-bipyridine, 1,2-bis(4-pyridyl)ethylene) in the presence of AgCF(3)SO(3). 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)(4)Os(4)(dhbq)(2)(4,4'-bipyridine)(2)](4+), shows an IC(50) value of 5.7 microM (comparable to cisplatin) against A2780 cancer cells and 7.5 microM against the cisplatin resistant A2780cisR cells.
Dalton Transactions 03/2010; 39(11):2816-20. · 3.84 Impact Factor
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ABSTRACT: The dinuclear dichloro complexes [(η6-arene)2Ru2(μ-Cl)2Cl2] and [(η5-C5Me5)2M2(μ-Cl)2Cl2] react with 2-(pyridine-2-yl)thiazole (pyTz) to afford the cationic complexes [(η6-arene)Ru(pyTz)Cl]+ (arene = C6H6 (1), p-iPrC6H4Me (2) or C6Me6 (3)) and [(η5-C5Me5)M(pyTz)Cl]+ (M = Rh (4) or Ir (5)), isolated as the chloride salts. The reaction of 2 and 3 with SnCl2 leads to the dinuclear heterometallic trichlorostannyl derivs. [(η6-p-iPrC6H4Me)Ru(pyTz)(SnCl3)]+ (6) and [(η6-C6Me6)Ru(pyTz)(SnCl3)]+ (7), resp., also isolated as the chloride salts. The mol. structures of 4, 5 and 7 have been established by single-crystal X-ray structure analyses of the corresponding hexafluorophosphate salts. The in vitro anticancer activities of the metal complexes on human ovarian cancer cell lines A2780 and A2780cisR (cisplatin-resistant), as well as their interactions with plasmid DNA and the model protein ubiquitin, have been investigated.
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ABSTRACT: The dinuclear dichloro complexes [(η6-arene)2Ru2(μ-Cl)2Cl2] and [(η5-C5Me5)2M2(μ-Cl)2Cl2] react with 2-(pyridine-2-yl)thiazole (pyTz) to afford the cationic complexes [(η6-arene)Ru(pyTz)Cl]+ (arene = C6H6 1, p-iPrC6H4Me 2 or C6Me6 3) and [(η5-C5Me5)M(pyTz)Cl]+ (M = Rh 4 or Ir 5), isolated as the chloride salts. The reaction of 2 and 3 with SnCl2 leads to the dinuclear heterometallic trichlorostannyl derivs. [(η6-p-iPrC6H4Me)Ru(pyTz)(SnCl3)]+ (6) and [(η6-C6Me6)Ru(pyTz)(SnCl3)]+ (7), resp., also isolated as the chloride salts. The mol. structures of 4, 5 and 7 have been established by single-crystal X-ray structure analyses of the corresponding hexafluorophosphate salts. The in vitro anticancer activities of the metal complexes on human ovarian cancer cell lines A2780 and A2780cisR (cisplatin-resistant), as well as their interactions with plasmid DNA and the model protein ubiquitin, have been investigated.
