title: Theoretical study of general base-catalyzed hydrolysis of aryl esters and implications for enzymatic reactions.
abstract: In this work, the mechanism of general base-catalyzed hydrolysis of aryl esters is investigated in vacuo with density functional theory and in solutions with a polarized continuum model. The hydrolysis is found to proceed via a concerted mechanism featuring simultaneous addition and elimination steps accompanied by proton transfers, consistent with experimental evidence. Reasonable agreement with measured kinetic isotope effects provides additional validation. It is found that solvation substantially lowers the transition state energy, but has a small effect on the reaction exothermicity. An enzyme oxyanion hole, modeled by an ammonia molecule hydrogen bonded to the acyl carbonyl oxygen, is found to stabilize the near-tetrahedral transition state. Implications of these findings for the hydrolysis step of the dehalogenation reaction catalyzed by 4-chlorobenzoyl-CoA dehalogenase are discussed.
authors.affiliation: Department of Chemistry, Institute of Theoretical and Computational Chemistry, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Daiqian
authors.initials: D
authors.lastname: Xie
authors.forename: Dingguo
authors.initials: D
authors.lastname: Xu
authors.forename: Lidong
authors.initials: L
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
mesh_terms: D002384:Catalysis; D004952:Esters / Q000737:chemistry*; D006868:Hydrolysis; D008962:Models, Theoretical
chemical_list: D004952:Esters