Effect of room temperature ionic liquid structure on the enzymatic acylation of flavonoids

Enzymatic acylation reactions of flavonoids (rutin, esculin) with long chain fatty acids (palmitic, oleic acids) were carried out in 14 different ionic liquid media containing a range of cation and anion structures. Classification of RTILs according to flavonoid solubility (using COSMO-RS) was the basis for structural selection. Overall, anion selection had a far greater influence on lipase activity than choice of cationic moiety. RTILs containing TF₂N⁻, PF₆⁻ and BF₄⁻ anions were most successful as reaction media while RTILs containing anions with stronger solvating properties (i.e. H-bonding ability) resulted in decreased yields, likely due to increased interactions with the protein structure of the lipase. Biosynthesis of rutin proceeded much slower than of esculin. All-in-all, judicious selection of RTILs was central to achieving high yields (>98% after 6 days for TOMA·TF₂N) since a balance must be struck that maximized flavonoid solubility with minimum negative impact on lipase activity. The process also benefitted from an increased reaction temperature which may have helped to reduced mass transfer limitations.