Modulating Biocatalytic Activity toward Sterically Bulky Substrates in CO₂‑Expanded Biobased Liquids by Tuning the Physicochemical Properties

The study of CO₂-expanded liquids using a green component such as a biobased solvent has been recently raised as a new concept for an alternative solvent and yet been largely unexplored in the literature for neither fundamental nor application studies. On the other hand, structural bulkiness of substrates remains one of the main limitations to promote enzymes as an efficient versatile catalytic tool for organic synthesis, especially biocatalysis in nonconventional solvents. Herein, we report a detailed investigation of CO₂-expanded biobased liquids as reaction media for improved biocatalysis of sterically hindered compounds. We found that CO₂ acts as a crucial trigger for various lipases to catalyze transesterification of challenging bulky alcohols in CO₂-expanded 2-methyltetrahydrofuran (MeTHF). Furthermore, this study determines the physicochemical and transport properties of CO₂-expanded MeTHF for the first time, which were then utilized for modulating biocatalytic activity. It was found that lipase activity increased with the accordingly decrease of the dipolarity of CO₂-expanded MeTHF, which is tunable by altering the concentration of CO₂ in the solvent system