Mickaël Ménand

An N-heterocyclic carbene ligand based on a β-cyclodextrin–imidazolium salt: synthesis, characterization of organometallic complexes and Suzuki coupling

A new ligand based on permethylated β-cyclodextrin bearing a methylimidazole group was synthesized. In the presence of this N-heterocyclic carbene ligand, silver or palladium complexes were generated. Interestingly, palladium species based on this ligand are more active than palladium species based on TPP or IMes,Cl for a Suzuki cross-coupling reaction.

Site-selective hexa-hetero-functionalization of alpha-cyclodextrin an archetypical C-6-symmetric concave cycle

Access to Cn (n>4) symmetric cyclic concave molecules with a different function on each of their n subunits is an unmet challenge. The reason lies in the lack of a post-functionalization method whose site selectivity is sufficiently understood, predictable and modulable to access most functionalization patterns. Here we disclose a new site-directing rule for a debenzylation reaction on cyclodextrins that solves this problem and allows the unprecedented access to penta- and ultimately hexa-differentiations of such C6 concave cycles. This achievement opens the access to objects with very high-density information.

An “Against the Rules” Double Bank Shot with Diisobutylaluminum Hydride To Allow Triple Functionalization of α-Cyclodextrin†

Frustration leads to overreaction: when diametrically opposed regioselective debenzylation is frustrated, an unexpected double debenzylation reaction affords original tetrafunctionalized cyclodextrins in a controlled and efficient manner. A rationale of the reaction is proposed based on a kinetic study.

Cyclodextrin Polyrotaxanes as a Highly Modular Platform for the Development of Imaging Agents

Selectively functionalized cyclodextrins with a bodipy fluorescent tag or Gd(3+) complex were synthetized and threaded onto a polyammonium chain to form polyrotaxanes. This modular supramolecular assembly makes an ideal platform for bimodal (fluorescent and MRI) imaging applications.

Hexaphyrin–Cyclodextrin Hybrids: A Nest for Switchable Aromaticity, Asymmetric Confinement, and Isomorphic Fluxionality

Conformational control over the highly flexible π-conjugated system of expanded porphyrins is a key step toward the fundamental understanding of aromaticity and for the development of molecular electronics. We have synthesized unprecedented hexaphyrin-cyclodextrin (HCD) capped hybrids in which the hexaphyrin part is constrained in a planar rectangular conformation in either a 26 or a 28 π-electron oxidation state ([26]/[28]HCD). These structures display strong aromaticity and antiaromaticity, respectively, exhibit markedly different chiroptical properties, and are interconvertible upon the addition of DDQ or NaBH(OAc)3, thus affording a rare switchable aromatic-antiaromatic system with a free-base expanded porphyrin. Conformational analysis revealed discrimination of the two coordination sites of the hexaphyrin, one of which was coupled to a confined asymmetric environment, and fluxional behavior consisting of apparent rotation of the hexaphyrin cap through a shape-shifting mechanism.

Cyclodextrins selectively modified on both rims using an O-3-debenzylative post-functionalisation, a consequence of the Sorrento meeting

A de-O-benzylation reaction induced by I(2)-Et(3)SiH and developed by Iadonisi et al. on mono- and disaccharides was applied to per- or polybenzylated α-cyclodextrins to furnish compounds deprotected at position 3 of all sugar units. This methodology allows the straightforward post-functionalisation of the secondary rim of cyclodextrins already functionalised on their primary rim.

Cyclodextrin Cavity‐Induced Mechanistic Switch in Copper‐Catalyzed Hydroboration

N-heterocyclic carbene-capped cyclodextrin (ICyD) ligands, α-ICyD and β-ICyD derived from α- and β-cyclodextrin, respectively give opposite regioselectivities in a copper-catalyzed hydroboration. The site-selectivity results from two different mechanisms: the conventional parallel one and a new orthogonal mechanism. The shape of the cavity was shown not only to induce a regioselectivity switch but also a mechanistic switch. The scope of interest of the encapsulation of a reactive center is therefore broadened by this study.

Mechanostereoselective One-Pot Synthesis of Functionalized Head-to-Head Cyclodextrin [3]Rotaxanes and Their Application as Magnetic Resonance Imaging Contrast Agents

A versatile, five-component, one-pot synthesis of cyclodextrin (CD) [3]rotaxanes using copper-catalyzed azide-alkyne cycloaddition has been developed. Head-to-head [3]rotaxanes of α-CD selectively functionalized by one or two gadolinium 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid monoamide complexes were obtained mechanostereoselectively. The magnetic resonance imaging efficiency, expressed by the longitudinal proton relaxivity of the rotaxanes, was significantly improved as compared to the functionalized CD. In vitro and in vivo preclinical studies showed a higher contrast and retention in the kidney than gadolinium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex, demonstrating the potential of these rotaxanes as MRI contrast agent.

Bridging β‐Cyclodextrin Prevents Self‐Inclusion, Promotes Supramolecular Polymerization, and Promotes Cooperative Interaction with Nucleic Acids

A bridge to assemble: Cyclodextrins bridged with an ammonium linker bearing a hydrophobic substituent can efficiently form supramolecular polymers and avoid the competing self-inclusion and head-to-head processes. Furthermore, the self-assembling cyclodextrin derivative interacts in a highly cooperative manner with DNA, as demonstrated by compaction experiments. It also interacts cooperatively with siRNA and allows its transfection.