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

Abstract

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][BF4] 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 (eep), and E value in 5% [Bmim][MeSO4] were 47.3%, >99%, and ∼300, respectively, the corresponding lipase stability is inadequate for commercial application. Excluding [Bmim][MeSO4], the lipase enantioselectivity increased with decreasing hydrogen bond basicity (β) 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 β value among all ILs examined, the E value was enhanced by a factor of 32. The conversion and eep 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.