Certified by:

(i) A new, quantitative model has been elaborated to rationalize the solvent dependence of enzymatic selectivity solely on the basis of the thermodynamics of substrate desolvation in the enzyme-bound transition state. The model predicts that any type of the selectivity (defined as the ratio of kcat/KM values) should be proportional to the ratio of the thermodynamic activity coefficients of the desolvated portions of the substrate(s) in the relevant transition state of the enzymatic reaction. The developed general model has been verified with prochiral selectivity of enzymes. Crystals (lightly cross-linked with glutaraldehyde) of the proteases y-chymotrypsin and subtilisin Carlsberg, used as asymmetric catalysts in organic solvents, almost quantitatively adhere to the predictions of the model in the acetylation of 2-substituted 1,3-propanediols. The solvent dependence of this prochiral selectivity is dominated by that of (kcat/KM)pro-R, which has been explained on the basis of a computer modeling analysis ofpro-R and pro-S transition-state structures. There is no correlation between the solvent-induced changes in kcat/KM values and those of either kcat or KM individually, presumably reflecting the complex nature of the latter tw