A thermodynamic study of ketoreductase-catalyzed reactions 4. Reduction of 2-substituted cyclohexanones in n-hexane

The equilibrium constants K for the ketoreductase-catalyzed reduction reactions (2-substituted cyclohexanone + 2-propanol = cis- and trans-2-substituted cyclohexanol + acetone) have been measured in n-hexane as solvent. The 2-substituted cyclohexanones included in this study are: 2-methylcyclohexanone, 2-phenylcyclohexanone, and 2-benzylcyclohexanone. The equilibrium constants K for the reactions with 2-methylcyclohexanone were measured over the range T = 288.15 to 308.05 K. The thermodynamic quantities at T = 298.15 K are: K = (2.13 ± 0.06); ΔrGm∘=-(1.87±0.06)kJ·mol-1; ΔrHm∘=-(6.56±2.68)kJ·mol-1; and ΔrSm∘=-(15.7±9.2)J·K-1·mol-1 for the reaction involving cis-2-methylcyclohexanol, and K = (10.7 ± 0.2); ΔrGm∘=-(5.87±0.04)kJ·mol-1; ΔrHm∘=-(2.54±1.8)kJ·mol-1; and ΔrSm∘=(11.2±6.4)J·K-1·mol-1 for the reaction involving trans  -2-methylcyclohexanol. The standard molar Gibbs free energy changes ΔrGm∘ for the reactions (trans-2-substituted cyclohexanol = cis-2-substituted cyclohexanol) in n-hexane have also been calculated and compared with the literature data that pertain to reactions in the gas phase and at higher temperatures. Experiments carried out with a chiral column demonstrated that the enzymatic reduction of 2-phenylcyclohexanone catalyzed by the ketoreductase used in this study is not stereoselective.