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-catalyzed hydrolysis and acylation reactions of racemic esters and alcohols has been determined. From the results we estimated the difference in activation enthalpy (δδH#) and activation entropy (δδS#) 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 δδH# versus δδS#-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.