Kinetics of lipase-catalyzed kinetic resolutions of racemic compounds: Reparameterization in terms of specificity constants

Abstract

Lipases, which catalyze reactions by the Ping Pong bi bi mechanism, are commonly used in kinetic resolutions to produce pure enantiomers. Although expressions for the relative rates of reaction of the two enantiomers in such resolutions are well known, they are difficult to interpret in terms of the reaction mechanism. In the current work, we reparameterize these expressions in terms of specificity constants, resulting in parameters that are easier to relate to the reaction mechanism. Expressions are derived for three different combinations of chiral substrates and products in a reaction “A + B ⇌ P + Q”: A-Q resolution, B-Q resolution and A-P resolution. We show that the relative rates of reaction of the enantiomers depend on key “decision points”, represented by the free and substituted enzymes. The relative rates of the various reactions that leave a “decision point” are determined by selectivities, which are given by ratios of specificity constants, multiplied by the ratio of concentrations of the corresponding species. The enantiomeric ratio is only one of these selectivities.