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Encapsulation of Photosensitizers in Hexa- and Octanuclear Organometallic Cages: Synthesis and Characterization of Carceplex and Host-Guest Systems in Solution
Cationic arene ruthenium assemblies of the general formulas [Ru6(p-cymene)6(tris-pvb)2(?2-Cl)6]6+, [Ru6(p-cymene)6(tris-pvb)2(OO?OO)3]6+ (tris-pvb = 1,3,5-tris{2-(pyridin-4-yl)vinyl}benzene), and [Ru8(p-cymene)8(NN?NN)2(OO?OO)4]8+ (NN?NN = 1,2,4,5-tetrakis{2-(pyridin-4-yl)vinyl}benzene, 1,2,4,5-tetrakis{2-(pyridin-4-yl)ethynyl}benzene) have been obtained from the corresponding dinuclear arene ruthenium complexes [Ru2(p-cymene)2(?-Cl)2Cl2] and [Ru2(p-cymene)2(OO?OO)Cl2] (OO?OO = oxalato, 2,5-dioxido-1,4-benzoquinonato, 2,5-dichloro-1,4-benzoquinonato, 5,8-dioxido-1,4-naphthoquinonato, 5,8-dioxido-1,4-anthraquinonato, 6,11-dioxido-5,12-naphthacenedionato) by reaction with the multidentate ligands and silver trifluoromethanesulfonate. These cationic hexa- and octanuclear cages have been isolated and characterized as their triflate salts. Addn. of coronene during the synthesis of the large hexanuclear assemblies leads to the direct encapsulation of coronene in the cavity of the trigonal-prismatic complexes. Photosensitizers such as porphin, phthalocyanine, and Zn-phthalocyanine present during the synthesis of these metalla-cages are encapsulated in five of these arene ruthenium complexes to give photosensitizer-encapsulated systems. The host-guest properties of these systems were studied in soln. by DOSY, 2D NOESY and 2D ROESY NMR spectroscopy. The H···H distances between guests and selected metalla-cages were estd. by 2D ROESY NMR spectroscopy and modelization. NMR analyzes indicate that the guest photosensitizers are completely encapsulated in two of these metalla-cages, while in the three other ruthenium cages NMR spectra reveal an equil. between empty and filled cages. [on SciFinder(R)]
Template-Directed Synthesis of Hexanuclear Arene Ruthenium Complexes with Trigonal-Prismatic Architecture Based on 2,4,6-Tris(3-pyridyl)triazine Ligands
Cationic arene ruthenium metalla-prisms of the general formula [Ru6(p-cymene)6(3-tpt)2(OO∩OO)3]6+ (3-tpt = 2,4,6-tris(3-pyridyl)-1,3,5-triazine; OO∩OO = 5,8-dioxido-1,4-naphthoquinonato [1]6+ or 6,11-dioxido-5,12-naphthacenedionato [2]6+) have been obtained from the corresponding dinuclear arene ruthenium complexes [Ru2(p-cymene)2(OO∩OO)Cl2] by reaction with 3-tpt, silver trifluoromethanesulfonate in the presence of an aromatic molecule (1,3,5-tribromobenzene, phenanthrene, pyrene, or triphenylene) that acts as a template. While the large template molecule triphenylene is permanently encapsulated in the metalla-prisms to give the complexes [triphenylene⊂1]6+ and [triphenylene⊂2]6+, 1,3,5-tribromobenzene can be removed in toluene, thus leaving the empty cages [1]6+ and [2]6+, which are isolated as their trifluoromethanesulfonate salts. In the case of the metalla-prism connected by the 5,8-dioxido-1,4-naphthoquinonato bridging ligands, the NMR spectrum reveals two isomers, 1a and 1b, the formation of which can be rationalized by means of multiple NMR experiments (one-dimensional, two-dimensional, ROESY, and DOSY). The empty and filled metalla-prisms, [1]6+, [2]6+, [template⊂1]6+, and [template⊂2]6+, have been characterized by NMR, UV−vis, and IR spectroscopy. The slow exchange processes of a guest molecule moving in and out of the cavity of cages [1]6+ and [2]6+ have been studied in solution with phenanthrene and pyrene. One-dimensional exchange spectroscopic (1D EXSY) measurements show that [phenanthrene⊂1]6+ is in a faster exchange regime than [phenanthrene⊂2]6+ and that phenanthrene is more easily exchanged than pyrene in cages [1]6+ and [2]6+, all observations being consistent with the portal size of the cages.
Designing the Host-Guest Properties of Tetranuclear Arene Ruthenium Metalla-Rectangles to Accommodate a Pyrene Molecule
Cationic tetranuclear arene ruthenium complexes of the general formula [Ru4(p-cymene)4(N∩N)2(dhnq)2]4+ comprising rectangular structures are obtained in methanol from the reaction of the dinuclear arene ruthenium precursor [Ru2(p-cymene)2(dhnq)2Cl2] (dhnq = 5,8-dihydroxy-1,4-naphthoquinonato) with pyrazine or bipyridine linkers [N∩N = pyrazine, 1; 4,4-bipyridine, 2; 1,2-bis(4-pyridyl)ethylene, 3] in the presence of AgCF3SO3. All complexes 1-3, isolated in good yield as triflate salts, have been characterised by NMR and IR spectroscopy. The interaction of these rectangular complexes with pyrene as a guest molecule has been studied in solution by various NMR techniques (1D, DOSY, ROESY). In [D3]acetonitrile, the pyrazine-containing metalla-rectangle 1 shows no meaningful interactions with pyrene. On the other hand, the 4,4-bipyridine- and 1,2-bis(4-pyridyl)ethylene-containing metalla-rectangles 2 and 3 clearly interact with pyrene in [D3]acetonitrile. DOSY measurements suggest that, in the case of [Ru4p-cymene)4(4,4-bipyridine)2(dhnq)2]4+ (2), the interactions occur on the outside of the rectangular assembly, while in the case of [Ru4(p-cymene)4{1,2-bis(4-pyridyl)ethylene}2 (dhnq)2]4+ (3), the pyrene molecule is found inside the hydrophobic cavity of the metalla-rectangle, thus giving rise to a host-guest system.
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.
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).
Complexes arène-ruthénium multinucléaires fluctuants: véhicules pour le transport intracellulaire de molécules cytotoxiques et photosensibilisantes
Depuis plusieurs années, la thérapie photo-dynamique est pratiquée au quotidien pour soigner certaines tumeurs, comme le mélanome. La méthode consiste à traiter le patient au moyen d’un composé photosensible, indifféremment absorbé par les cellules normales et cancéreuses, ces dernières le retenant toutefois plus longtemps. Après plusieurs heures, le composé est activé par une exposition à la lumière, provenant généralement d’un laser. L’approche est moins invasive que la radiothérapie ou la chimiothérapie. Elle a pour principal avantage de ne détruire que les zones éclairées par le laser, en l’occurrence les cellules tumorales, préservant ainsi la plupart des tissus sains.
La difficulté principale de cette technique réside dans la faible solubilité des substances photosensibles et de leurs réactivités accidentelles due à leurs excitations par la lumière du jour, causant des lésions cutanées non désirées. Les cages arène-ruthénium synthétisées durant ce travail de thèse permettent d’encapsuler des molécules photosensibles afin de les rendre solubles dans l’eau, mais aussi de protéger ces molécules photosensibles contre toute excitation lumineuse inopinée. De par son encapsulation dans la cage, la substance photosensible ne devient donc active qu’après sa libération de la cage et à condition d’être excitée par un laser approprié.
Ce travail de thèse a permis le passage des systèmes d’inclusion permanente aux systèmes « hôte-invité », mais il a également permis l’extension de l’encapsulation d’agents anticancéreux à l’encapsulation de photosensibilisateurs. Plusieurs types de cages arène-ruthénium ont été synthétisés dans lesquelles ont été encapsulées trois différentes molécules photosensibles : la porphine, la phthalocyanine et la zinc-phthalocyanine. Pour le moment, des tests in vitro n’ont été effectués que sur la porphine et ont permis de déterminer une très forte activité anticancéreuse de cette molécule pour une faible exposition au laser, ce qui prouve la bonne libération de l’agent photosensibilisant dans les cellules cancéreuses. Ce travail de thèse a donc contribué au développement de complexes arène-ruthénium multinucléaires en tant que véhicules pour le transport intracellulaire de molécules cytotoxiques et photosensibilisantes.
Bimetallic ruthenium–tin chemistry: Synthesis and molecular structure of arene ruthenium complexes containing trichlorostannyl ligands
A series of neutral, anionic and cationic arene ruthenium complexes containing the trichlorostannyl ligand have been synthesised from SnCl2 and the corresponding arene ruthenium dichloride dimers [(η6-arene)Ru(μ2-Cl)Cl]2 (arene = C6H6, PriC6H4Me). While the reaction with triphenylphosphine and stannous chloride only gives the neutral mono(trichlorostannyl) complexes [(η6-C6H6)Ru(PPh3)(SnCl3)Cl] (1) and [(η6-PriC6H4Me)Ru(PPh3)(SnCl3)Cl] (2), the neutral di(trichlorostannyl) complex [(η6-PriC6H4Me)Ru(NCPh)(SnCl3)2] (3) could be obtained for the para-cymene derivative with benzonitrile as additional ligand. By contrast, the analogous reaction with the benzene derivative leads to a salt composed of the cationic mono(trichlorostannyl) complex [(η6-C6H6)Ru(NCPh)2(SnCl3)]+ (5) and of the anionic tris(trichlorostannyl) complex [(η6-C6H6)Ru(SnCl3)3]− (6). On the other hand, [(η6-PriC6H4Me)Ru(μ2-Cl)Cl]2 reacts with SnCl2 and hexamethylenetetramine hydrochloride or 18-crown-6 to give the anionic di(trichlorostannyl) complex [(η6-PriC6H4Me)Ru(SnCl3)2Cl]− (4), isolated as the hexamethylenetetrammonium salt or the chloro-tin 18-crown-6 salt. The single-crystal X-ray structure analyses of 1, 2, [(CH2)6N4H][4], [(18-crown-6)SnCl][4] and [5][6] reveal for all complexes a pseudo-tetrahedral piano-stool geometry with ruthenium–tin bonds ranging from 2.56 (anionic complexes) to 2.60 Å (cationic complex).