Catalysis of an Aldol Condensation Using a Coordination Cage

Abstract

The aldol condensation of indane-1,3-dione (ID) to give 'bindone' in water is catalysed by an M 8 L 12 cubic coordination cage (H w ). The absolute rate of reaction is slow under weakly acidic conditions (pH 3-4), but in the absence of a catalyst it is undetectable. In water, the binding constant of ID in the cavity of H w is ca. 2.4 (±1.2) × 10 3 M −1 , giving a ∆G for the binding of −19.3 (±1.2) kJ mol −1 . The crystal structure of the complex revealed the presence of two molecules of the guest ID stacked inside the cavity, giving a packing coefficient of 74% as well as another molecule hydrogen-bonded to the cage's exterior surface. We suggest that the catalysis occurs due to the stabilisation of the enolate anion of ID by the 16+ surface of the cage, which also attracts molecules of neutral ID to the surface because of its hydrophobicity. The cage, therefore, brings together neutral ID and its enolate anion via two different interactions to catalyse the reaction, which-as the control experiments show-occurs at the exterior surface of the cage and not inside the cage cavity.

Design and Applications of Water-Soluble Coordination Cages

“…Here, the surface of the cage is proposed to bring the neutral substrate together with its enolate anion. 356 …”

Orthogonal binding and displacement of different guest types using a coordination cage host with cavity-based and surface-based binding sites

“…More recently, we 5,6 and others 7,8 have noticed that the exterior surfaces of cages also provide recognition sites for, principally, ionic guests. The same characteristics of the interior surface of a cage (hydrophobicity arising from organic ligand components; charge density arising from metal ion vertices; possibly the presence of functional groups) that facilitate guest binding can also exist at the exterior surfaces.…”

“…Thus, cavity-binding of a neutral hydrophobic guest, and electrostatically-driven surface-binding of hydroxide ions, cooperate very effectively to promote catalysis by co-locating the two reaction partners using different interactions: even under weakly basic conditions (pH 8 in bulk solution) the accumulation of hydroxide ions at the cage surface, surrounding the cavity-bound guest, is such that the local pH in the cavity is effectively 13–14. 5 a …”

Supramolecular Chemistry in the 3rd Millennium

“…Supramolecular interactions are critical to selective binding within receptor molecules and host-guest chemistry, and several papers illustrate these principles using hydroquinonebased anion receptors (Gale and coworkers) [3], cucurbit [7]uril (Redshaw and coworkers) [4] and self-assembled n-alkyl-benzoureido-15-crown-5-ethers as selective ion-channels for K + cations (Barboiu and coworkers) [5]. Dalgarno and coworkers contribute with a fascinating investigation of cage assembly using p-t Bu-calix [4]arene building blocks [6].…”

“…Dalgarno and coworkers contribute with a fascinating investigation of cage assembly using p-t Bu-calix [4]arene building blocks [6]. Catalysis carried out within the confines of molecular or supramolecular cages is a topical area, and Ward and his coauthors describe a beautiful example exploiting a cubic M 8 L 12 coordination cage [7]. The assembly of highly symmetric metal-cyclo-tricatechylene cages supported within a three-dimensional cubic hydrogen-bonded network is described by Abrahams and coworkers [8].…”