Investigation of solvent effects for the Claisen rearrangement of chorismate to prephenate: mechanistic interpretation via near attack conformations.
ABSTRACT Solvent effects on the rate of the Claisen rearrangement of chorismate to prephenate have been examined in water and methanol. The preequilibrium free-energy differences between diaxial and diequatorial conformers of chorismate, which had previously been implicated as the sole basis for the observed 100-fold rate increase in water over methanol, have been reframed using the near attack conformation (NAC) concept of Bruice and co-workers. Using a combined QM/MM Monte Carlo/free-energy perturbation (MC/FEP) method, 82%, 57%, and 1% of chorismate conformers were found to be NAC structures (NACs) in water, methanol, and the gas phase, respectively. As a consequence, the conversion of non-NACs to NACs provides no free-energy contributions to the overall relative reaction rates in water versus methanol. Free-energy perturbation calculations yielded differences in free energies of activation for the two polar protic solvents and the gas phase. The rate enhancement in water over the gas phase arises from preferential hydration of the transition state (TS) relative to the reactants via increased hydrogen bonding and long-range electrostatic interactions, which accompany bringing the two negatively charged carboxylates into closer proximity. More specifically, there is an increase of 1.3 and 0.6 hydrogen bonds to the carboxylate groups and the ether oxygen, respectively, in going from the reactant to the TS in water. In methanol, the corresponding changes in hydrogen bonding with first shell solvent molecules are small; the rate enhancement arises primarily from the enhanced long-range interactions with solvent molecules. Thus, the reaction occurs faster in water than in methanol due to greater stabilization of the TS in water by specific interactions with first shell solvent molecules.
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ABSTRACT: LynF, an enzyme from the TruF family, O-prenylates tyrosines in proteins; subsequent Claisen rearrangements give C-prenylated tyrosine products. These reactions in tyrosines and model phenolic systems have been explored with DFT and SCS-MP2 calculations. Various ab initio benchmarks have been used (CBS-QB3, MP2, SCS-MP2) to examine the accuracy of commonly used density functionals, such as B3LYP and M06-2X. Solvent effects from water were considered by using implicit and explicit models. Studies of the ortho-C-prenylation and Claisen rearrangement of tyrosine, and the Claisen rearrangement of α,α-dimethylallyl (prenyl) coumaryl ether establish the energetics of these reactions both in the gas phase and in aqueous solution.European Journal of Organic Chemistry 05/2013; 2013(14-14):2823-2831. · 3.15 Impact Factor
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ABSTRACT: Combined quantum mechanics/molecular mechanics (QM/MM or QM-MM) methods are an excellent approach for modelling the mechanisms of enzyme-catalysed reactions. QM/MM methods allow detailed modelling of reactions in enzymes by coupling quantum chemical calculations on the active site with a simpler, empirical `molecular mechanics' treatment of the rest of the protein. Possible reaction mechanisms can be compared and catalytic interactions analysed. QM/MM calculations can now be carried out for enzyme-catalysed reactions with quantum chemical methods of potentially very high accuracy. More approximate QM methods can allow extensive molecular simulations (e.g. molecular dynamics or Monte Carlo simulations). In this review, QM/MM techniques are outlined and some recent applications to enzyme-catalysed reactions are discussed.International Reviews in Physical Chemistry 01/2010; 29:65-133. · 4.92 Impact Factor
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ABSTRACT: In the course of the ozonolysis of the bicyclo[2.2.1]heptene anhydride 1, the three bis-lactones 3–5 have been obtained (the structures were confirmed by X-ray crystallographic analysis).Tetrahedron Letters 07/2009; 50(26):3385-3387. · 2.39 Impact Factor