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Propriétés mésomorphes ou biologiques d'assemblages dendritiques et métallodendritiques
Ce travail traite de l’incorporation de métaux dans des assemblages dendritiques pour obtenir des propriétés liquides-cristallines ou biologiques.
L’arrangement spatial des nanoparticules d’or est actuellement un défi pour obtenir des métamatériaux. Les associer à des dendrimères liquides-cristallins est une possibilité pour les organiser dans des mésophases. Nous avons mis en place une nouvelle méthodologie de synthèse basée sur la réaction de métathèse croisée. Le greffage de dendrons par métathèse croisée a permis d’obtenir des dendrimères symétriques ou non symétriques qui présentent des phases liquides-cristallines. L’influence de cette fonction chimique sur les propriétés mésomorphes a pu être étudiée. Des résultats préliminaires ont été obtenus concernant le greffage de nanoparticules d’or par les dendrons utilisés précédemment. Il a été possible d’échanger à la surface de l’or des ligands, introduisant de nouveaux sites réactionnels pour de futures réactions de métathèse croisée. La dernière étape s’est avérée difficile à réaliser. Cependant, les premiers essais ont montré des résultats encourageants dans la synthèse de tels édifices moléculaires.
Des métallodendrimères ont été synthétisés par encapsulation dans des complexes organométalliques hydrosolubles à base d’arènes ruthénium. Pour cela, divers dendrimères ont été fonctionnalisés au niveau du cœur par une unité pyrényle. L’encapsulation de ces dérivés par l’unité pyrényle a été caractérisée par de nombreuses techniques analytiques. Les composés à base de cages de forme rectangulaire ont permis de développer une nouvelle famille de métallomésogènes. Des phases cubiques ont été obtenues. L’influence de la flexibilité du complexe organométallique et de ses contre ions s’est révélée déterminante. Le comportement antiprolifératif des composés à base de cages de forme prismatique a été étudié in vitro envers différentes lignées de cellules cancéreuses. Il a ainsi été possible de véhiculer des dendrimères insolubles dans l’eau jusque dans les cellules.,
The aim of this thesis is to combine metals and dendrimers to obtain mesomorphic or biological properties.
The design of metamaterials from gold nanoparticles is still a challenge as the spatial organisation is difficult to control. Thus, the combination of gold nanoparticles with liquid-crystalline dendrimers is a way to explore the organisation of such systems in mesophases. We have developed a new synthetic methodology based on the well known cross-metathesis reaction. Some symmetric or non-symmetric dendritic materials have been synthesised and were used to study the influence of this chemical function on the liquid-crystalline properties. Preliminary results have been obtained for the functionalisation of gold nanoparticles by dendrons. It has been possible to exchange ligands on the surface of gold nanoparticles in order to add new functional sites for further metathesis reaction. The graft of dendrons on gold nanoparticles has been unsuccessful; however, the first trials have shown interesting results in the synthesis of such molecular assemblies.
Metallodendritic assemblies have been synthesised via encapsulation in water-soluble arene ruthenium metalla-complexes. A pyrenyl unit has been grafted on the apex of dendrimers and has then been encapsulated in the cavity of the cages. Many analytical techniques have been used to study these host-guest systems. A new family of metallomesogens has been observed with the complexes based on a rectangular cage. Cubic mesophases have been obtained. The influence of the flexibility of the organometallic complex and of the counterions has been decisive. The antiproliferative behaviour of the compounds based on prismatic cages has been established in vitro towards different cancer cell lines. It has been possible to transport non water-soluble dendrimers inside cells.
Designing Supramolecular Liquid-Crystalline Hybrids from Pyrenyl-Containing Dendrimers and Arene Ruthenium Metallacycles
The association of the arene ruthenium metallacycle [Ru4(p- cymene)4(bpe)2(donq)2][DOS]4 (bpe = 1,2- bis(4-pyridyl)ethylene, donq = 5,8-dioxydo-1,4-naphtoquinonato, DOS = dodecyl sulfate) with pyrenyl-functionalized poly(arylester) dendrimers bearing cyanobiphenyl end- groups is reported. The supramolecular dendritic systems display mesomorphic properties as revealed by polarized optical microscopy, differential scanning calorimetry and small- angle X-ray scattering measurements. The multicomponent nature of the dendrimers and of the corresponding host–guest supramolecules (i.e., end-group mesogens, dendritic core, pyrene unit, aliphatic spacers, and metallacycle) leads to the formation of highly segregated mesophases with a complex multilayered structure due to the tendency of the various constitutive building-blocks to separate in different organized zones. The pyrenyl dendrimers exhibit a multilayered smectic A-like phase, thereafter referred to as LamSmA phase to emphasize this unaccustomed morphology. As for the corresponding Ru4–metallacycle adducts, they self-organize into a multicontinuous thermotropic cubic phase with the Im3¯m space group symmetry. This represents a unique example of liquid- crystalline behavior observed for such large and complex supramolecular host–guest assemblies. Models of their supramolecular organizations within both mesophases are proposed.
Encapsulation of Pyrene-Functionalized Poly(benzyl ether) Dendrons into a Water-Soluble Organometallic Cage
Two generations of lipophilic pyrenyl functionalized poly(benzyl ether) dendrimers (P1 and P2) have been synthesized. The thermal properties of the two functionalized dendrimers have been investigated, and the pyrenyl group of the dendritic molecules encapsulated in the arene–ruthenium metalla-cage, [Ru6(p-cymene)6(tpt)2(donq)3]6+ ([1]6+) (tpt=2,4,6-tri(pyridin-4-yl)-1,3,5-triazine; donq=5,8-dioxydo-1,4-naphthoquinonato). The host–guest properties of [P1⊂1]6+ and [P2⊂1]6+ were studied in solution by NMR and UV/Vis spectroscopic methods, thus allowing the determination of the affinity constants. Moreover, the cytotoxicity of these water-soluble host–guest systems was evaluated on human ovarian cancer cells.
Enhancement of Cytotoxicity by Combining Pyrenyl-Dendrimers and Arene Ruthenium Metallacages
Three generations of pyrenyl bis-MPA dendrimers with two different end-groups, acetonide (pyrGn) or alcohol (pyrGn-OH) (n = 1–3), were synthesized, and the pyrenyl group of the dendritic molecules was encapsulated in the arene ruthenium metallacages, [Ru6(p-cymene) 6 (OO∩OO)3(tpt)2]6+ (OO∩OO = 5,8-dioxydo- 1,4-naphtaquinonato (donq) [1]6+ and 6,11-dioxydo-5,12- naphtacenedionato (dotq) [2]6+; tpt =2,4,6-tri(pyridin-4-yl)-1,3,5-triazine). The host–guest properties of [guestC1]6+ and [guestC2]6+ were studied in solution by NMR and UV–vis spectroscopic methods, thus allowing the determination of the affinity constants. Moreover, the cytotoxicity of these water- soluble host–guest systems and the pyrenyl-dendrimers was evaluated on human ovarian cancer cells.
Double Targeting of Tumours with Pyrenyl-Modified Dendrimers Encapsulated in an Arene–Ruthenium Metallaprism
The self-assembly of 2,4,6-tris(pyridin-4-yl)-1,3,5-triazine (tpt) triangular panels with p-cymene–ruthenium building blocks and 5,8-dioxido-1,4-naphthoquinonato (donq) bridges, in the presence of pyrenyl-containing dendrimers of different generations (P0, P1 and P2), affords the triangular prismatic host–guest compounds [Pn⊂Ru6(p-cymene)6(tpt)2(donq)3]6+ ([Pn⊂1]6+). The host–guest nature of these systems, with the pyrenyl moiety being encapsulated in the hydrophobic cavity of the cage and the dendritic functional group pointing outwards, was confirmed by NMR spectroscopy (1H, 2D and DOSY). The host–guest properties of these systems were studied in solution by NMR and UV/Vis spectroscopic methods, allowing the determination of their affinity constants (Ka). Moreover, the ability of these water-soluble host–guest systems to carry the pyrenyl-containing dendrimers into cancer cells was evaluated on human ovarian cancer cells. The host–guest systems are all more cytotoxic than the empty cage [1][CF3SO3]6 (IC50≈4 μM), with the most active compound, [P0⊂1][CF3SO3]6, being an order of magnitude more cytotoxic.