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Accueil > Thèmes de recherche > Chimie, Imagerie et Exobiologie > Assemblages moléculaires et systèmes complexes

Assemblages moléculaires et systèmes complexes

par Frapart - publié le , mis à jour le

DESCRIPTIF DU TRAVAIL DE RECHERCHE

A. Complexes polymétalliques auto-assemblés

Les composés polynucléaires de lanthanides peuvent être avantageusement préparés en utilisant une approche synthétique supramoléculaire 10.
La préparation de systèmes auto-assemblés stables et solubles dans l’eau, où de nombreux facteurs doivent être pris en compte est une tâche difficile. Dans ce contexte, un effort dans la conception et la synthèse de ligands appropriés a été réalisé afin de fournir et de caractériser des précurseurs (ligands polytopiques et leur complexes) pour des applications en imagerie. Des études détaillées de spéciation thermodynamique de complexes supramoléculaires avec différents cations lanthanide sont effectuées par RMN et différentes méthodes spectroscopiques.

Complexes supramoléculaires de lanthanides 9

B. Oligonucléotides modifiés

De nouvelles familles d’oligonucléotides originaux sont développées en vue d’obtenir des outils pour la recherche fondamentale, le diagnostic in vitro, l’imagerie biologique ainsi que des agents thérapeutiques potentiels.
La réalisation de ces différents objectifs nécessite l’utilisation d’oligonucléotides qui doivent posséder un certain nombre de propriétés. En fonction des applications, les oligonucléotides doivent, en effet, posséder plusieurs des propriétés suivantes : former des complexes spécifiques et stables avec leurs cibles, induire des modifications irréversibles des cibles par pontage ou coupure, produire un signal modifié en présence des cibles utilisable comme preuve de l’interaction. De plus, dans le cas des applications en culture cellulaire et in vivo, ils doivent être stables vis-à-vis des nucléases et être capables d’atteindre leurs cibles à l’intérieur des cellules 11.
Afin de conférer aux oligonucléotides des propriétés adaptées en fonction des applications, nous modifions chimiquement leurs éléments structuraux (bases nucléiques, sucres, liaisons internucleotidiques). A ces oligonucléotides peuvent être fixés différents ligands : molécules intercalantes et/ou réactives, peptides, molecules lipophiles, inhibiteurs de topoisomérases, marqueurs fluorescents détectables dans le visible et NIR….). Le développement de conjugués possédant des propriétés optimales dépend des paramètres de liaison entre les deux entités (positions de liaison sur l’oligonucléotide et le ligand, longueur et nature du bras de liaison). La synthèse chimique de ces nouvelles séries d’oligonucléotides nécessite le développement de nouveaux réactifs et méthodes de synthèse.

Exemples de modifications des oligonucléotides
  • 9 - Zebret S. ; Vögele E., Klumpler T. and Hamacek J.
    Designing Artificial 3D Helicates : Unprecedented Self-Assembly of Homo-Octanuclear
    Tetrapods with Europium. Chem. Eur. J. (2015) 21, 6695-6699 - doi : 10.1002/chem.201500006
  • 10 - Hamacek J.
    Self-assembly Principles of Helicates, in Metallofoldamers : Supramolecular Architectures from Helicates to Biomimetics. Eds. : Albrecht M. and, Maayan G., Wiley (2013) - doi : 10.3389/fchem.2013.00015
  • 11 - Asseline U., Goncalves C., Pichon C. and Midoux M.
    Improved nuclear delivery of antisense 2’-Ome RNA by conjugation with the histidine-rich peptide H5WYGarticle. J. Gene Med. (2014) 16, 157-165 - doi : 10.1002/jgm.2773

Principales publications

  • Vuillamy A., Zebret S., Besnard C., Placide V., Petoud S. and Hamacek J.
    Functionalized Triptycene-Derived Tripodal Ligands : Privileged Formation of Tetranuclear Cage Assemblies with Larger Ln(III). Inorg. Chem. (2017) 56, 2742-2749 - doi : 10.1021/acs.inorgchem.6b02900.
  • Hamacek J. and Vuillamy A.
    Controlling the Structures of Lanthanide Complexes in Self-Assemblies with Tripodal Ligands. Eur. J. Inorg. Chem., (2017) - doi : 10.1002/ejic.201701075.
  • El Aroussi B. and Hamacek J.
    Understanding the Speciation of Ln(III) Complexes with Octadentate Tripodal Ligands. New J. Chem. (2017) 41, 4390-4399 - doi : 10.1039/C7NJ00088J
  • Zebret S., Vogele E., Besnard C. and Hamacek J.
    Synthetic routes to large tripodal organic receptors and the structural characterisation of intermediates. Tetrahedron (2016) 72, 928-935 - doi : 10.1016/j.tet.2015.12.048

Membres du groupe thématique

HAMACEK Josef Professeur de l’Université d’Orléans, Responsable du groupe thématique@

MATIC Marin - stagiaire Master 2

BEAUVAIS Valentin - stagiaire Master 1

KHIAL Boualem - stagiaire DUT


Page du groupe


Publications

2018   Références trouvées : 1

Hamacek J., Vuillamy A., Peterhans L., Homberg A., Poggiali D., W. Schneider M. W. and Mastalerz M.  (2018)

Ln(III) complexes with triptycene based tripodal ligands : speciation and equilibria

New Journal of Chemistry (2018 ) 42 (10) 7803-7809
Triaminotriptycene was used as a rigid anchoring platform for preparing several organic ligands for Ln(III) complexation. In this work we present detailed speciation studies with a tripodal ligand L6 possessing terminal carboxamide coordinating moieties. The solution speciation for different [Ln]/[L] ratios is investigated using NMR and mass spectrometry and compared with those of closely related ligands L7 and L8. A special interest is devoted to chemical equilibria in metal excess, whereby different complex species are generated through slow transformations. The effect of the ionic radius along the lanthanide series is discussed for tetranuclear and trinuclear complexes.

Triaminotriptycene was used as a rigid anchoring platform for preparing several organic ligands for Ln(III) complexation. In this work we present detailed speciation studies with a tripodal ligand L6 possessing terminal carboxamide coordinating moieties. The solution speciation for different [Ln]/[L] ratios is investigated using NMR and mass spectrometry and compared with those of closely related ligands L7 and L8. A special interest is devoted to chemical equilibria in metal excess, whereby different complex species are generated through slow transformations. The effect of the ionic radius along the lanthanide series is discussed for tetranuclear and trinuclear complexes.


2017   Références trouvées : 3

Vuillamy A., Zebret S., Besnard C., Placide V., Petoud S. and Hamacek J.  (2017)

Functionalized Triptycene-Derived Tripodal Ligands : Privileged Formation of Tetranuclear Cage Assemblies with Larger Ln(III).

Inorganic Chemistry (2017) 56, 2742-2749.
In this Article, we report the self-assembly of lanthanide complexes formed with two new tripodal ligands, L2 and L3, where binding strands are connected to a rigid triptycene anchor. The pyridine moieties are functionalized with methoxy and PEG groups to enhance ligand solubility and to evaluate the effect of these substituents on lanthanide coordination. These ligands were successfully synthesized and characterized, and their coordination properties were examined along the lanthanide series through speciation studies with NMR and ESI-MS. Well-defined tetranuclear complexes are formed with both ligands, but their stabilities with heavier lanthanides are considerably reduced, especially for complexes with L3. This is attributed to a destabilizing effect of pending PEG arms in combination with increased steric hindrance between binding strands upon complexation with smaller cations. The sensitization of lanthanide luminescence in tetranuclear complexes occurs despite one water molecule being coordinated to a metal ion.

In this Article, we report the self-assembly of lanthanide complexes formed with two new tripodal ligands, L2 and L3, where binding strands are connected to a rigid triptycene anchor. The pyridine moieties are functionalized with methoxy and PEG groups to enhance ligand solubility and to evaluate the effect of these substituents on lanthanide coordination. These ligands were successfully synthesized and characterized, and their coordination properties were examined along the lanthanide series through speciation studies with NMR and ESI-MS. Well-defined tetranuclear complexes are formed with both ligands, but their stabilities with heavier lanthanides are considerably reduced, especially for complexes with L3. This is attributed to a destabilizing effect of pending PEG arms in combination with increased steric hindrance between binding strands upon complexation with smaller cations. The sensitization of lanthanide luminescence in tetranuclear complexes occurs despite one water molecule being coordinated to a metal ion.

Hamacek J. and Vuillamy A.  (2017)

Controlling the Structures of Lanthanide Complexes in Self-Assemblies with Tripodal Ligands.

European Journal of Inorganic Chemistry (2017)
The complexity of self-assembled supramolecular systems is continuously evolving in the direction of large multicomponent polynuclear architectures. The self-assembly of such systems requires the preparation of sophisticated organic receptors with “programmed” multidentate sites for binding metal ions. In this review we focus on the concept of tripodal receptors specifically designed for complexing lanthanide cations. A large palette of polytopic podands is described, and the structures of their anchoring and binding moieties are discussed together with their impact on the self-assembly with LnIII. The crystal or calculated structures of mononuclear and polynuclear complexes are shown to illustrate typical structural features in relation to their properties. Moreover, thermodynamic speciation with several ligands is analysed along the lanthanide series in order to ascertain the effects of the ionic size. Understanding and controlling the different factors discussed here should help in rational designing of more complex architectures with LnIII.

The complexity of self-assembled supramolecular systems is continuously evolving in the direction of large multicomponent polynuclear architectures. The self-assembly of such systems requires the preparation of sophisticated organic receptors with “programmed” multidentate sites for binding metal ions. In this review we focus on the concept of tripodal receptors specifically designed for complexing lanthanide cations. A large palette of polytopic podands is described, and the structures of their anchoring and binding moieties are discussed together with their impact on the self-assembly with LnIII. The crystal or calculated structures of mononuclear and polynuclear complexes are shown to illustrate typical structural features in relation to their properties. Moreover, thermodynamic speciation with several ligands is analysed along the lanthanide series in order to ascertain the effects of the ionic size. Understanding and controlling the different factors discussed here should help in rational designing of more complex architectures with LnIII.

El Aroussi B. and Hamacek J.  (2017)

Understanding the speciation of Ln( iii ) complexes with octadentate tripodal ligands.

Journal of Chemistry (2017) 41, 4390 - 4399.
Two new dissymmetrical tripodal ligands bearing three multidentate pyridine moieties (L5 and L6) have been synthesised and the speciation of their Ln(III) complexes in solution has been studied. The complexation behaviour with selected Ln(III) has been investigated by combining ESMS, spectrophotometric and NMR titrations. For both ligands LX (X = 5, 6), the Ln2(LX)3 species are abundantly present at stoichiometry in the form of unconventional low-symmetrical complexes. However, the complexes with L5 at [Ln]/[L5] ∼1 are much better defined and allow the corresponding 1H-NMR spectrum to be completely assigned. Indeed, the latter points out that the structure of complexes [Ln2(L5)2]6+ in solution is best described as an unsaturated dinuclear helicate, where the tridentate sites are wrapped about the metallic cations, and the bidentate strand does not coordinate. Compared to L4 and L6, the prolongation of the spacer in L5 (glycine moiety) has in fact allowed thermodynamic and kinetic stabilities to increase, especially for the Lu(III) complexes. Finally, the structure of dinuclear species [Ln2(LX)2]6+ (X = 4–6) is apparently independent of the structure of the bidentate moieties, which are involved in complexation in metal excess only.

Two new dissymmetrical tripodal ligands bearing three multidentate pyridine moieties (L5 and L6) have been synthesised and the speciation of their Ln(III) complexes in solution has been studied. The complexation behaviour with selected Ln(III) has been investigated by combining ESMS, spectrophotometric and NMR titrations. For both ligands LX (X = 5, 6), the Ln2(LX)3 species are abundantly present at stoichiometry in the form of unconventional low-symmetrical complexes. However, the complexes with L5 at [Ln]/[L5] ∼1 are much better defined and allow the corresponding 1H-NMR spectrum to be completely assigned. Indeed, the latter points out that the structure of complexes [Ln2(L5)2]6+ in solution is best described as an unsaturated dinuclear helicate, where the tridentate sites are wrapped about the metallic cations, and the bidentate strand does not coordinate. Compared to L4 and L6, the prolongation of the spacer in L5 (glycine moiety) has in fact allowed thermodynamic and kinetic stabilities to increase, especially for the Lu(III) complexes. Finally, the structure of dinuclear species [Ln2(LX)2]6+ (X = 4–6) is apparently independent of the structure of the bidentate moieties, which are involved in complexation in metal excess only.


2016   Références trouvées : 1

Zebret S., Vögele, E., Besnard C. and Hamacek J.  (2016)

Synthetic routes to large tripodal organic receptors and the structural characterisation of intermediates

Tetrahedron (2016) 72 (7) 928-935 - doi : 10.1016/j.tet.2015.12.048
This contribution explores synthetic routes adopted and optimized for the preparation of three new hexatopic tripodal organic ligands designed for Ln(III) complexation. In these ligands, three strands bearing two pyridyldicarbonyl binding moieties are anchored with a small aliphatic triamine. The described synthesis is not straightforward and depends on the nature of the spacer between coordinating moieties. In addition to the characterisation of targeted ligands, the structure of ditopic intermediates is assessed by X-ray crystallography and discussed with respect to the spacer nature.

This contribution explores synthetic routes adopted and optimized for the preparation of three new hexatopic tripodal organic ligands designed for Ln(III) complexation. In these ligands, three strands bearing two pyridyldicarbonyl binding moieties are anchored with a small aliphatic triamine. The described synthesis is not straightforward and depends on the nature of the spacer between coordinating moieties. In addition to the characterisation of targeted ligands, the structure of ditopic intermediates is assessed by X-ray crystallography and discussed with respect to the spacer nature.


2015   Références trouvées : 1

Zebret S., Vogele E., Klumpler T. and Hamacek J.  (2015)

Designing artificial 3D helicates : unprecedented self-assembly of homo-octanuclear tetrapods with europium

Chemistry - A European Journal (2015) 21 (18) 6695-6696 - doi : 10.1002/chem.201500006
Herein, we report on the rational design, preparation and characterization of a novel homo-octanuclear helicate, which results from a spatial extension of the central tetranuclear platform. The 3D supramolecular assembly is obtained by complexing europium(III) with a new hexatopic tripodal ligand. The isolated octanuclear helicate is fully characterized by different methods clearly evidencing the structure predicted with molecular modelling. The ligand preorganization plays a crucial role in a successful self-assembly process and induces the formation of a well-defined triple-stranded helical structure. This prototypal octanuclear edifice accommodating functional lanthanides within a 3D scaffold offers attractive perspectives for further applications.

Herein, we report on the rational design, preparation and characterization of a novel homo-octanuclear helicate, which results from a spatial extension of the central tetranuclear platform. The 3D supramolecular assembly is obtained by complexing europium(III) with a new hexatopic tripodal ligand. The isolated octanuclear helicate is fully characterized by different methods clearly evidencing the structure predicted with molecular modelling. The ligand preorganization plays a crucial role in a successful self-assembly process and induces the formation of a well-defined triple-stranded helical structure. This prototypal octanuclear edifice accommodating functional lanthanides within a 3D scaffold offers attractive perspectives for further applications.