Cope in a Capsule

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Science  11 Aug 2006:
Vol. 313, Issue 5788, pp. 735-737
DOI: 10.1126/science.313.5788.735d

One goal of self-assembly research is to prepare synthetic structures of sufficient complexity to achieve the remarkable catalytic rate accelerations and selectivities characteristic of enzymes. Fiedler et al. explore the capacity of self-assembled tetrahedral capsules to catalyze a unimolecular reaction—the 3-aza Cope rearrangement of allyl enammonium cations. Each capsule is composed of four gallium centers bridged by catecholamide ligands and bears a 12-negative charge that attracts the cationic reagent to the interior but reduces affinity for the neutral hydrolyzed product.

The authors previously found that the capsules induced ∼100-fold to ∼1000-fold rate increases relative to the uncatalyzed reaction; temperature-dependent kinetic studies of an ethyl-bearing substrate suggested that the acceleration was due purely to decreased entropy of activation. Extending the kinetic studies to additional substrates reveals that although entropy factors continue to play a major role, in some cases the capsules reduce activation enthalpy as well. Analysis of nuclear Overhauser effects in nuclear magnetic resonance spectra supports a mechanism in which the capsule binds substrates in particularly reactive conformations. Additional kinetic studies at variable hydroxide concentration suggest that the hydrolysis step takes place outside the capsule, through the intermediacy of a tight ion pair. Because the capsules are chiral, the authors suggest that further refinement may allow efficient diastereoselection or enantioselection in reactions of substrates that lack binding sites for more traditional molecular catalysts. — JSY

J. Am. Chem. Soc. 128, 10.1021/ja062329b (2006).

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