Resolution of Ibuprofen Enantiomers by Rhizomucor miehei Lipase (RML) Immobilized via Physical and Covalent Attachment

Ibuprofen, 4-isobutyl-propionic acid, is an important well-known member of NSAIDs which is widely utilized in inflammatory therapy like treatment of rheumatoid arthritis and various degrees of analgesic. Despite the high medical activity and low toxicity of ibuprofen, it is supplied as a racemic mixture. In this research enantioselective resolution of (R, S)-ibuprofen by immobilized preparations of Rhizomucor miehei lipase (RML) on silica and silica nanoparticles was investigated. For this, chemical modification of silica and silica mesoporous nanoparticles was performed by the simultaneous use of two coupling linkers; Octyltriethoxysilane (OTES) for hydrophobic interaction and glycidoxypropyltrimethoxylsilane (GPTMS) for covalent linkage of RML. The results showed that immobilization of RML on octyl-functionalized supports produces specific activity almost 1.5-2 folds greater than the specific activity of the free enzyme. The observed hyper-activation decreased with increasing epoxy groups on the supports confirming the enhancement of covalent nature of the attachment. Regarding the specific activity of the immobilized preparations and desorption percentages of RML from each support, the most suitable carrier obtained from the functionalization of the supports in the presence of GPTMS and OTES in the ratio of 1:1. The selected biocatalysts were then used for enantioselective resolution of (R, S)-ibuprofen by esterification reaction at different conditions. The results revealed that the most suitable biocatalysts are those prepared by immobilization of RML on SBA-15 and silica modified with GPTMS and OTES in the ratio of 1:1 which produced high E values at ambient temperature.