P. Barton et al., STRUCTURE-ACTIVITY-RELATIONSHIPS IN THE ESTERASE-CATALYZED HYDROLYSISAND TRANSESTERIFICATION OF ESTERS AND LACTONES, Perkin transactions. 2, (9), 1994, pp. 2021-2029
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.