Highly efficient catalysis of the Kemp elimination in the cavity of a cubic coordination cage

• Published in: Nature chemistry Vol. 8; no. 3; pp. 231 - 236
• Main Authors: Cullen, William, Misuraca, M. Cristina, Hunter, Christopher A., Williams, Nicholas H., Ward, Michael D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2016; Nature Publishing Group
• Subjects: 140/131; 639/638/541/965; 639/638/77/888; Analytical Chemistry; Biochemistry; Catalysis; Chemistry; Chemistry/Food Science; Inorganic Chemistry; Ions; Organic Chemistry; Physical Chemistry
• ISSN: 1755-4330; 1755-4349
• DOI: 10.1038/nchem.2452

The hollow cavities of coordination cages can provide an environment for enzyme-like catalytic reactions of small-molecule guests. Here, we report a new example (catalysis of the Kemp elimination reaction of benzisoxazole with hydroxide to form 2-cyanophenolate) in the cavity of a water-soluble M 8 L 12 coordination cage, with two features of particular interest. First, the rate enhancement is among the largest observed to date: at pD 8.5, the value of k cat / k uncat is 2 × 10 5 , due to the accumulation of a high concentration of partially desolvated hydroxide ions around the bound guest arising from ion-pairing with the 16+ cage. Second, the catalysis is based on two orthogonal interactions: (1) hydrophobic binding of benzisoxazole in the cavity and (2) polar binding of hydroxide ions to sites on the cage surface, both of which were established by competition experiments. The Kemp elimination has been catalysed in the cavity of a coordination cage with a rate enhancement ( k cat / k uncat ) of 200,000 at pD 8.5. The catalysis requires two orthogonal interactions to bring together the components: hydrophobic binding of benzisoxazole, and accumulation of hydroxide ions at the cationic cage surface by ion-pairing.