Kinetic modelling of lipase-catalyzed remote resolution of citalopram intermediate in solvent-free system

The kinetic modelling of Candida antarctica lipase B catalyzed remote resolution of a tertiary alcohol, citalopram intermediate (diol), was studied using vinyl acetate as acylating agent in solvent-free system. The diffusion limitation and enzyme deactivation were proved to be negligible. A kinetic model based on ping-pong bi–bi mechanism with competitive substrates using King–Altman method was proposed. The substrate inhibition by each enantiomer of diol and the spontaneous transesterification were also considered. Following model discrimination and the application of Haldane equations to reduce the degree of freedom in parameter estimation, the 11 free parameters were successfully identified. Kinetic parameters were estimated using time–concentration curves of different diol concentrations and the simulated values fitted the experimental values well with an average relative error of 12.8%. Furthermore, the developed model was used to investigate the effect of diol concentration on reaction enantioselectivity by the prediction of the typical plot of enantiomeric excess versus conversion of substrate. The average relative error between the results predicted and experimental data was 13.1%.