Ionic liquids as cosolvents for the lipase-catalyzed kinetic resolution of ketoprofen

This study examined the use of ionic liquids (ILs) as cosolvents for the Candida rugosa lipase-catalyzed enantioselective hydrolysis of racemic ketoprofen ethyl ester. To determine the effect of the IL anion structures on the lipase activity and enantioselectivity, six ILs containing the 1-butyl-3-methylimidazolium ([Bmim]) cation were used as cosolvents and their solvent properties were correlated with various reaction characteristics. The highest lipase activities were obtained using [Bmim] (BF 4 ] and [Bmim][MeSO4] as cosolvents. The enantioselectivity (E) of lipase was enhanced by a factor of 50 with 5% [Bmim][MeSO4]. Although the conversion, enantiomeric excess of product (ee(p)), and E value in 5% [Bmim][MeSO4] were 47.3%, > 99%, and similar to 300, respectively, the corresponding lipase stability is inadequate for commercial application. Excluding [Bmim] [MeSO4], the lipase enantioselectivity increased with decreasing hydrogen bond basicity (beta) of the IL when the log E values of lipase in 5% ILs were correlated with IL solvent parameters. With [Bmim] [PF6] as the cosolvent, which has the lowest beta value among all Its examined, the E value was enhanced by a factor of 32. The conversion and ee(p )in 20% [Bmim] [PF6] were 48.0% and 96.9%, respectively. Additionally, the lipase stability in aqueous [Bmim] [PF6] solution was much higher than that in aqueous [Bmim] [MeSO4] solution.