Abstract
We performed a computational investigation of the mechanism by which cyclodextrins (CDs) catalyze Diels-Alder reactions between 9-anthracenemethanol and N-cyclohexylmaleimide. Hydrogen bonds (Hbonds) between N-cyclohexylmaleimide and the hydroxyl groups of cyclodextrins were suggested to play an important role in this catalytic process. However, our free energy calculations and molecular dynamics simulations showed that these Hbonds are not stable, and quantum mechanical calculations suggested that the reaction is not promoted by these Hbonds. The binding of 9-anthracenemethanol and N-cyclohexylmaleimide to cyclodextrins was the key to the catalytic process. Cyclodextrins act as a container to hold the two reactants in the cavity, pre-organize them for the reactions, and thus reduce the entropy penalty to the activation free energy. Dimethyl-β-CD was a better catalyst for this specific reaction than β-CD because of its stronger van der Waals interaction with the pre-organized reactants and its better performance in reducing the activation energy. This computational work sheds light on the mechanism of the catalytic reaction by cyclodextrins and introduces new perspectives of supramolecular catalysis.
Highlights
Supramolecular catalysts offer potential advantages over enzymes, including greater physical and chemical stability, lower molecular weight, and a far more varied selection of chemical versatility for the creation of structure and functionality
Β-CD/dimethyl-β-CD complex examined which which reactant bound to a cyclodextrin first by computing the binding free energies of or
The driving force of the catalysis is not the Hydrogen bonds (Hbonds) between cyclodextrins and 2a because of the low occurrence of the Hbonds suggested by VM2 and MD results; Intrinsic Reaction Coordinates (IRC) calculations yielded small differences with or without the Hbonds
Summary
Supramolecular catalysts offer potential advantages over enzymes, including greater physical and chemical stability, lower molecular weight, and a far more varied selection of chemical versatility for the creation of structure and functionality. Due to their unique chemical and physical properties, cyclodextrins are useful in pharmaceutical, food, and agricultural industries [1,2,3,4,5]. The Diels-Alder reaction is an important carbon–carbon bond formation reaction in organic synthesis It forms two carbon–carbon bonds and up to four new stereo centers in one step.
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