Metallocavitands DOI: 10.1002/anie.201301225 NHC-Capped Cyclodextrins (ICyDs): Insulated Metal Complexes, Commutable Multicoordination Sphere, and Cavity-Dependent Catalysis** Maxime Guitet, Pinglu Zhang, Filipa Marcelo, Coralie Tugny, Jesffls JimØnez-Barbero, Olivier Buriez, Christian Amatore, Virginie Mouris-Mansuy, Jean-Philippe Goddard, Louis Fensterbank, Yongmin Zhang, Sylvain Roland, Mickal MØnand, and Matthieu Sollogoub* Metal centers associated with cavities have attracted much attention, mainly because of their resemblance to metallo- enzymes. [1] Among concave molecules with a cavity, cyclo- dextrins (CDs) are unique owing to their natural occurrence, their hydrosolubility, and the structure of their cavity. Unlike any other cavity, in particular those based on aromatic rings, their interior is carpeted with hydrogen atoms, which confer hydrophobicity and introduce additional van der Waals interactions. Therefore, CDs are widely used to host hydro- phobic molecules in polar solvents. The possibility of con- verting cyclodextrins into enzyme mimics very soon attracted the interest of scientists. [2] More specifically, for CDs to be used to mimic metalloenzymes, a metal must be attached to the CD scaffold. [3] Owing to the size of the cavity, two different ways to append the metal can be considered for the study of two different phenomena. First, the metal can be positioned at the entrance of the cavity to exploit the inclusion ability of the cavity in its interaction with a substrate and mimic the binding pocket of an enzyme (Figure 1 a). Second, the metal can be encapsulated inside the cavity to study the effect of confinement on its coordination sphere and chemical properties; this arrangement mimics the environ- ment of a metal buried deeply within a folded protein (Figure 1 b). The first kind of design has been widely studied, often with the attachment of a metal–ligand unit through a single linkage. [3] Such structures can be used in a multitude of applications, for example, in catalysis. [4] However, for the metal center to be fixed directly above the cavity, double linkage of the metal was necessary. In the resulting so-called metal-capped CDs, [5, 6] the metal ion is located right on top of the CD cavity. [7] The deepest position in which the metal has been placed so far intercepts the plane defined by the C-6 atoms of the sugar units. [8, 9] This metal position leaves the cavity available for the inclusion of guests. The cavity can thus serve as a host for substrates (the interaction of which with the metal center can lead to an acceleration of the reaction rate [10] in analogy with an enzymatic reaction), as a probe for ligand exchange, [8] or as a second coordination sphere through C  H···X  M interactions. [11] For metallocyclodextrins of the second kind, in which the metal center occupies the middle of the cavity like an included guest, typically at the level of the H-5 atoms, only noncovalent inclusion complexes of metal ions have been described so far. Their electrochemical properties have been studied thoroughly, and electron transfer is thought not to involve the included complex, but the free portion of non- included metallic guest ions. [12] In other words, no studies on cyclodextrin complexes in which the metal ion is forced through covalent bonding to be included deep inside the Figure 1. In a metal-capped cyclodextrin, the cavity interacts either a) with the substrate or b) with the metal, depending on the depth of inclusion. [*] M. Guitet, P. Zhang, C. Tugny, Dr. V. Mouris-Mansuy, Dr. J.-P. Goddard, Prof. L. Fensterbank, Dr. Y. Zhang, Dr. S. Roland, Dr. M. MØnand, Prof. M. Sollogoub UPMC UniversitØ Paris 06, Sorbonne UniversitØs Institut Universitaire de France, LabEx MiChem, IPCM UMR CNRS 7201, C181, 4, place Jussieu, F-75005 Paris (France) E-mail: matthieu.sollogoub@upmc.fr Homepage: http://www.ipcm.fr/Presentation,293 Dr. F. Marcelo, Prof. J. JimØnez-Barbero Chemical and Physical Biology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas Ramiro de Maeztu 9, 28040 Madrid (Spain) Dr. F. Marcelo REQUIMTE, CQFB, Departamento de Química Faculdade de CiÞncias e Tecnologia, UNL 2829-516 Caparica (Portugal) Dr. O. Buriez, Prof. C. Amatore Ecole Normale SupØrieure, DØpartement de Chimie UMR CNRS-ENS-UPMC 8640 “PASTEUR” 24 rue Lhomond, Paris cedex 05 F-75231 (France) [**] We thank Cyclolab (Hungary) and Roquette (France) for generous supplies of a-CD and b-CD, respectively, and the Agence Nationale de la Recherche (Supra-HierArchi Project ANR-Blanc, SIMI 7-2012) for financial support. NHC = N-heterocyclic carbene. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201301225. A ngewandte Chemi e 7213 Angew. Chem. Int. Ed. 2013, 52, 7213 –7218  2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim