A kinetic and thermodynamic study of the lipase-catalyzed remote resolution of a chiral tertiary alcohol

• Published in: Biochemical Engineering Journal
• Main Authors: Wang, Shi-Zhen, 王世珍, Wu, Jian-Ping, Xu, Gang, Yang, Li-Rong
• Format: Article in Journal/Newspaper
• Language: English
• Published: ELSEVIER SCIENCE SA 2012
• Subjects: Dynamic modeling; Kinetic parameters; Lipase; Immobilized enzymes; Tertiary alcohol; Asymmetric alcoholysis; Antarc*; Antarctica
• Online Access: https://doi.org/10.1016/j.bej.2012.04.005; http://dspace.xmu.edu.cn/handle/2288/15258

The kinetics and thermodynamics of Candida antarctica lipase B-catalyzed remote asymmetric alcoholysis of the citalopram intermediate 3-[(acetyloxy)methyl]-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-benzonitrile (diol monoacetate) have been studied. A kinetic model based on the reversible ping-pong bi-bi mechanism with competitive enantiomer substrates was proposed. The product inhibition by each diol enantiomer and the substrate inhibition by isobutyl alcohol were also considered. The diffusion limitation was proven to be negligible. By reducing the degree of freedom in parameter estimation by model discrimination and Haldane equations, 14 free parameters were successfully identified. The model parameters were simulated by the Matlab program using time-concentration curves of different diol monoacetate concentrations; the simulated values fit the experimental values well, with an average relative error of 9.6%. The reaction activity and enantioselectivity of C. antarctica lipase B toward the tertiary alcohol were investigated by kinetic and thermodynamic analysis using simulated kinetic parameters. (c) 2012 Elsevier B.V. All rights reserved. National Natural Science Foundation of China [20936002]; Key Project of Chinese National Programs for Fundamental Research and Development [2011CB710800]; Hi-Tech Research and Development Program of China [2011AA02A209]