Partenaires

CNRS


Rechercher


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

THÉMATIQUES DE RECHERCHE

Les activités de recherche de notre groupe sont principalement axées sur la conception, la synthèse et la caractérisation de systèmes moléculaires et supramoléculaires de complexité variée. Nous nous intéressons à une meilleure compréhension des facteurs structurels, des interactions intra et intermoléculaires, des équilibres thermodynamiques et cinétiques au sein de ces assemblages ou mélanges, et de leur exploitation pour les applications biomédicales et l’imagerie, les nanomatériaux et la cosmétique. Notre approche est interdisciplinaire et nécessite des compétences en chimie, biochimie et biophysique. Quelques sujets de recherche sont présentés plus en détail ci-dessous, mais cette liste n’est pas exhaustive. Si vous souhaitez nous rejoindre (à un niveau quelconque : étudiant, chercheur, etc.), n’hésitez pas à nous contacter. Vous trouverez les informations actuelles sur notre site web.

Complexes polymétalliques auto-assemblés

Les composés polynucléaires avec les lanthanides peuvent être avantageusement préparés en utilisant une approche synthétique supramoléculaire. La préparation de systèmes stables auto-assemblés, où de nombreux facteurs doivent être pris en compte, n’est pas une tâche facile. Dans ce contexte, un effort a été fait dans la conception et la synthèse de ligands appropriés pour fournir et caractériser des précurseurs (ligands polytopiques et leurs complexes) pour différentes applications. Des études de spéciation thermodynamique détaillées de complexes supramoléculaires avec différents cations de lanthanides sont effectuées par la RMN et des méthodes spectroscopiques différentes (voir par exemple Inorg. Chem., 2017, 56 (5), 2742-2749). Entre les réalisations les plus importantes, nous pouvons souligner l’auto-assemblage des hélicates octanucléaires Ln8L4 (Chem. Eur. J. 2015, 21, 6695-6699).

Complexes supramoléculaires de lanthanides

La majorité de nos ligands sont des "tripodes" (ligands tripodes) qui peuvent former, en principe, des complexes de Ln(III) disposant de structures et de nucléarités différentes. Récemment, nous avons publié un article de revue à ce sujet dans le European Journal of Inorganic Chemistry (Eur J. Inorg Chem., 2018 (10), 1155-1166), et notre article a été sélectionné pour la première page du journal.

Par ailleurs, les principes thermodynamiques des auto-assemblages avec les lanthanides ont été discutés en détail dans le livre “Metallofoldamers : Supramolecular Architectures from Helicates to Biomimetics.” (Eds. : Albrecht M. and, Maayan G., Wiley 2013).

Cinétique enzymatique dans les milieux complexes

Ce travail est réalisé en collaboration avec Francesco Piazza et son groupe. Nous étudions les réactions enzymatiques (mais pas seulement) dans différents milieux complexes qui ressemblent les environnements biologiques / cellulaires. Les composants de ces milieux peuvent interagir avec des composants actifs (enzymes, substrats) et influencer de manière significative les vitesses de réaction ou les voies métaboliques. Les interactions sont étudiées avec des méthodes biophysiques appropriées impliquant une installation de rayonnement synchrotron (SOLEIL).

Bio-assemblages hybrides

Ici, notre intérêt est concentré sur la préparation d’assemblages biologiquement actifs en utilisant des "ancres chimiques". Cette approche permet un meilleur contrôle de la topologie et de la spécificité de tels systèmes. Leurs applications en ciblage biologique ou en imagerie sont multiples et sont actuellement en cours d’exploration.

Oligonucléotides modifiés

De nouvelles familles d’oligonucléotides originaux ont été récemment développées afin de fournir des outils pour la recherche fondamentale, le diagnostic in vitro, l’imagerie biologique et les agents thérapeutiques potentiels. Selon l’application, les oligonucléotides doivent en effet présenter plusieurs des propriétés suivantes : former des complexes spécifiques et stables avec leurs cibles, induire des modifications irréversibles des cibles par pontage ou clivage, produire un signal modifié en présence de cibles utilisables comme interaction de preuve. De plus, dans le cas d’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 (J. Gene Med., 2014, 16, 157-165). Afin de conférer des propriétés spécifiques aux oligonucléotides pour des applications ciblées, nous modifions chimiquement leurs éléments structuraux (bases nucléiques, sucres, liaisons inter-nucléotidiques (longueur et nature)). A ces oligonucléotides peuvent être attachés divers ligands : molécules intercalantes et/ou réactives, peptides, molécules lipophiles, inhibiteurs, marqueurs fluorescents détectables.

Exemples de modifications des oligonucléotides

Site web du groupe


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


Publications

2018   Références trouvées : 2

Hamacek J. and Vuillamy A.  (2018)

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

European Journal of Inorganic Chemistry (2018) 2018 (10) 1155-1166.
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.

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.