Theoretical Study of Chemoselectivity of Acetylene Hydrates

Density functional theory (DFT) was used to study the chemoselectivity of acetylene hydratase in hydration of 3-butyn-2-ol, propargyl alcohol and propen. A quite large model of the enzyme’s active site was made, based on its crystal structure. Geometrical structures of the stationary points along the reaction paths were optimized, and energy profiles of the reactions were obtained. The results showed that the binding energy of 3-butyn-2-ol is 16.1 kcal/mol higher than the binding energy of the enzyme’s normal substrate (acetylene), but the corresponding reactant is 17.4 kcal/mol more stable. Similarly, propargyl alcohol’s binding energy is 10.7 kcal/mol more than binding energy of acetylene. In the third step of the reaction, propargyl alcohol reaches to a very stable intermediate and its reaction stops. These show that 3-butyn-2-ol and propargyl alcohol act as competitive inhibitors of acetylene hydratase. The results showed that binding of propen is very endothermic than binding of the other compounds (30.3 kcal/mol). In addition, the next nucleophilic attack is also very endothermic. In summary, propen cannot be hydrated by acetylene hydratase.