Application of structure-based thermodynamic calculations to the rationalization of the enantioselectivity of subtilisin in organic solvents

The effect of organic solvents on the selectivity of lyophilized or CLEC
(cross-linked enzyme crystals)-subtilisin in the resolution of
sec-phenethyl alcohol and trans-sobrerol was studied. A theoretical
model, that tries to predict solvent effects on enantioselectivity only
as a function of the activity coefficients of the desolvated part of the
substrate in the relevant transition state of the reaction (Ke, T.;
Wescott, C. R.; Klibanov, A. M. J. Am. Chem. Sec., 1996, 118, 3366) was
examined and shown to agree poorly with the experimental data. The
tetrahedral intermediate was studied with MonteCarlo molecular
mechanics, and the activity coefficients were calculated with UNIFAC.
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