Effect of co‐solvent addition on the reaction kinetics of the lipase‐catalyzed resolution of ibuprofen ester

Abstract

BACKGROUND: The addition of co‐solvent is not limited to enhancing the catalytic rate, it could also assist in situ racemization in the dynamic kinetic resolution of racemic compounds by increasing the reactivity of the base catalyst employed. In the current work, reaction media with the presence of DMSO were investigated in Candida rugosa lipase (EC 3.1.1.3)‐catalyzed hydrolysis of ibuprofen ester that focuses on the thermodynamic effect, reaction stability and implication for the kinetic parameters. RESULTS: The introduction of 2% DMSO increased the reaction rate, conversion, and enantioselectivity of the Candida rugosa lipase‐mediated resolution. However, the performance of the particular enzymatic reaction was reduced when a higher DMSO concentration was added. At lower reaction temperatures, the medium with 2% DMSO exhibited an increase in enantioselectivity, which was attributed to a higher activation energy difference between the fast‐ and slow‐reacting enantiomers compared with the water‐isooctane medium. Additionally, the presence of DMSO had a significant effect on the kinetic parameters, shown by a lower value of Michaelis constant compared with that of a normal reaction without DMSO, which resulted in a fast reaction rate. Finally, inhibition due to the uncompetitive substrate inhibitor was reduced, while the non‐competitive product inhibitor consequently increased. CONCLUSION: This work has demonstrated that only 2% of DMSO can be tolerated by the free Candida rugosa lipase in the resolution of ibuprofen ester. However, it is still able to give significant positive effects on the hydrolysis rate, kinetic parameters and enantioselectivity as well as reaction stability. © 2012 Society of Chemical Industry

Lipase‐catalyzed hydrolysis of (+,‐)‐2‐(4‐methylphenyl) propionic methyl ester enhanced by hydroxypropyl‐β‐cyclodextrin

“…7 Until now, the dominant chiral preparation technology in industry has remained enantiomeric separation. A series of methods for enantiomeric separation, such as crystallization, 8,9 chromatography, 10,11 membrane separation, 1,12 enantioselective liquid-liquid extraction (ELLE), [13][14][15] and enzymatic kinetic resolution, [16][17][18][19][20][21][22][23][24][25][26] have been developed. Crystallization is still the most frequently applied technology for the manufacture of active pharmaceutical ingredients (APIs).…”

Factors screening to statistical experimental design of racemic atenolol kinetic resolution via transesterification reaction in organic solvent using free Pseudomonas fluorescens lipase

“…Many lipases were employed to resolve the racemic atenolol via the transesterification reaction as given in Table . At the beginning of the experiments, an organized screening process was prepared by focusing the enzymatic reactions on the free enzymes from Candida antarctica lipase of fraction B (CALB), Candida rugosa lipase (CRL), and lipase PS (PSL) since they are frequently used to resolve the racemic compounds . However, these enzymes cannot be used, as low results are produced, which are not acceptable.…”

“…At the beginning of the experiments, an organized screening process was prepared by focusing the enzymatic reactions on the free enzymes from Candida antarctica lipase of fraction B (CALB), Candida rugosa lipase (CRL), and lipase PS (PSL) since they are frequently used to resolve the racemic compounds. 18,[25][26][27][28][29][30][31][32][33][34] However, these enzymes cannot be used, as low results are produced, which are not acceptable. Hence, the racemic atenolol resolution was finally conducted through a blind screening process until a suitable enzyme was discovered.…”

Advances in Bioprocess Technology

“…This is due to the fact that some enzyme molecules are unable to exhibit maximum performance in some polar solvents (Fu and Vasudevan 2010). Meanwhile the addition of dimethyl sulfoxide has slightly decreased the activity of lipase during the hydrolysis of ibuprofen ester (Gonawan et al 2013b). An intense research is in progress to achieve maximum activity of enzyme in the immobilized form as well as in the extreme media environment.…”

“…In the following section, the DEKR process is hypothetically studied by manipulation of process variables incorporated as dimensionless constants in the developed models. The input parameters are presented in Table 16.3 (Gonawan et al 2013b;Lau et al 2010;Lau 2013). …”