STRUCTURE-ACTIVITY-RELATIONSHIPS IN THE ESTERASE-CATALYZED HYDROLYSISAND TRANSESTERIFICATION OF ESTERS AND LACTONES

The Bronsted exponents for the alkaline hydrolysis of alkyl esters are 1.3 and 0.4 for substitution in the acyl and alcohol portions, respec tively, which is indicative of a transition state which resembles the anionic tetrahedral intermediate with a localised negative charge. By contrast, the rate of the pig liver esterase (PLE)-catalysed hydrolysi s shows little dependence upon the electron-withdrawing power of subst ituents. The values of k(cat) are independent of the pK(a) of the leav ing group alcohol suggesting rate-limiting deacylation. There is a sma ll steric effect of alpha-substitution in both the alcohol and carboxy lic acid residues for the enzyme-catalysed reactions but the enzyme ra te enhancement factor remains high for most esters. There is no substa ntial ee observed for the hydrolysis of racemic esters although the ki netic data can be used for determining the regioselective hydrolysis o f diesters. Unsubstituted lactones are poor substrates for PLE but der ivatives with hydrophobic substituents show k(cat)/K-m values similar to those for acyclic esters. Dihydrocoumarin undergoes transesterifica tion catalysed by PLE, k(cat) increases with increasing alcohol concen tration indicative of rate-limiting deacylation. There is enantioselec tivity in the PLE-catalysed hydrolysis of some racemic lactones but li ttle or none in the transesterification of racemic alcohols with dihyd rocoumarin.