The temperature dependence of enzymatic kinetic resolutions reveals the relative contribution of enthalpy and entropy to enzymatic enantioselectivity

The temperature dependence of the enantioselectivity of several lipase-calalyzed hydrolysis and acylation reactions of racemic esters and alcohols has been determined. From the results we estimated the difference in activation enthalpy (Delta Delta H-# and activation entropy (Delta Delta S-#) for the two enantiomers in the enantioselective reaction step. Contrary to earlier suggestions, we found that the enthalpic and entropic contributions to the enantioselectivity are of similar magnitude. A plot of Delta Delta H-# versus Delta Delta S-#-values of data available in the literature for various enzyme-substrate combinations revealed a tempting correlation between the enthalpic and entropic contributions. This observation would imply enthalpy-entropy compensation to be a general feature of enantioselective enzymatic catalysis. On closer inspection of the data set it was realized that this trend must be considered fortuitous. It originates from the non-random collection of those enzyme-substrate combinations for which the numerical value of the enantiomeric ratio can be measured with a suitable degree of accuracy at ambient temperatures. Indications for the occurrence of genuine enthalpy-entropy compensation, however, have been observed for series of homologous substrates and changes of solvent composition.