Metal centers associated with cavities have attracted much attention, mainly because of their resemblance to metalloenzymes.[1] Among concave molecules with a cavity, cyclodextrins (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 hydrophobic molecules in polar solvents. The possibility of converting 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 environment 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 À H···X À 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 nonincluded 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....

A series of capped metallo-cyclodextrins were synthesized, affording a variety of artificial chiral metallo-pockets through modulation of the space around the metal. Carbene ligands were used as caps for placing a silver, gold, or copper center at a well-defined location inside the cyclodextrin cavity. Multiple weak interactions involving the d 10 metal center and intra-cavity hydrogen atoms, including anagostic interactions, were observed in solution. Thus, the metal was used as a probe for assessing intra-cavity metal-H distances for building 3D models, revealing the very different shapes of capped a-, band nd g-cyclodextrins and the helical shape of the chiral pocket of some modified cyclodextrins. This series of N-heterocyclic-carbene-based cyclodextrins were compared in gold-catalyzed cycloisomerization reactions, for which the 3D models were used to rationalize the observed regio-and stereoselectivities.

Access to C n (n44) 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 C 6 concave cycles. This achievement opens the access to objects with very high-density information.

Geschlossene Gesellschaft: Mit einem N‐heterocyclischen Carben überdeckte Cyclodextrine (ICyDs) binden in ihrem Hohlraum Metallionen unter Beteiligung von X⋅⋅⋅π‐Wechselwirkungen, was ein Verschließen des Hohlraums durch Ligandenaustausch ermöglicht (siehe Schema; Bn=Benzyl). Obwohl kein elektrischer Kontakt mit einer Elektrode besteht, behalten die tief vergrabenen Metallionen ihre katalytische Aktivität. Der Hohlraum beeinflusste den regio‐ und stereochemischen Verlauf der katalysierten Reaktionen.

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High-throughput UV-vis titrations in combination with chemical double-mutant cycles (DMCs) have been used to study the competition of a polar solvent for formation of intramolecular H-bonds. Twenty-four different zinc porphyrin-pyridine complexes were investigated in mixtures of toluene and phenol. DMCs were used to determine effective molarities (EM) for the formation of intramolecular phenol-amide H-bonds as a function of solvent composition. The values of EM increase by an order of magnitude with increasing concentrations of the more polar solvent, phenol. Phenol solvates the amide groups on the ligands strongly, increasing the steric bulk and destabilizing the complexes. These adverse steric interactions are removed when intramolecular H-bonds are formed and therefore provide an increased driving force for formation of cooperative interactions. The result is that the effects of competitive interactions with polar solvents that reduce binding affinity are attenuated to a significant extent by a corresponding increase in EM in multivalent complexes.

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.

Frustration führt zur Überreaktion: Wenn die regioselektive Debenzylierung an entgegengesetzten Positionen verhindert ist, führt eine unerwartete doppelte Debenzylierung effizient zu vierfach funktionalisierten Cyclodextrinen. Eine kinetische Studie liefert eine Erklärung für diese Reaktion.