ENTHALPIC AND ENTROPIC CONTRIBUTIONS TO LIPASE ENANTIOSELECTIVITY

The enantioselective properties of lipases in the kinetic resolution o f chiral substrates are conveniently expressed as the enantiomeric rat io, E. It has been stated that E is related to the difference of the G ibbs free energy of activation of the enantioselective reaction steps by RT In E=-Delta Delta G(#)=T Delta Delta S-#-Delta Delta H-#. From t he temperature dependence of E we estimated the enthalpic, Delta Delta H-#, and entropic, Delta Delta S-#, contributions. Contrary to earlie r suggestions (Aqvist, J. and Warshel, A., 1993. Simulation of enzyme reactions using valence bond force fields and other hybrid quantum/cla ssical approaches. Chem. Rev. 93, 2523-2544.) it is found that the ent ropic contribution, T Delta Delta S-#, to lipase enantioselectivity at ordinary temperatures is significant. Plots of Delta Delta H-# versus Delta Delta S-# for enzyme-catalyzed kinetic resolutions reported in the literature, show a tempting linear correlation of the enthalpic an d entropic contributions. On closer inspection, we realized that this is the result of a non-random selection of systems. Hairpin curves are observed for plots of the enthalpic and entropic contributions to lip ase-catalyzed enantioselective reactions in water-cosolvent mixtures a nd in organic media as a function of medium composition. The importanc e of these findings for the fundamental understanding of enzyme enanti oselectivity, the rationalization of solvent effects on the enantiomer ic ratio and the prediction of lipase enantioselectivity by molecular modeling techniques is discussed. (C) 1998 Elsevier Science Ireland Lt d. All rights reserved.