Prochiral selectivity in H2O2-promoted oxidation of arylalkanols catalysedby chloroperoxidase - The role of the interactions between the OH group and the amino-acid residues in the enzyme active site

The H2O2-promoted oxidations of (R)-[alpha-H-2(1)]-and (S)-[alpha-H-2(1)]-a rylalkanols catalysed by chloroperoxidase (CPO) from Caldariomyces fumago h ave been investigated. It has been found that with (R)-[alpha-H-2(1)]-alcoh ols, the oxidation involves almost exclusively the cleavage of the C-H bond , whereas in the case of the oxidation of (S)-[alpha-H-2(1)]alcohols, the C -D bond is preferentially broken. These results clearly indicate that the r eactions of corresponding undeuterated arylalkanols are characterized by a high prochiral selectivity, involving the cleavage of the pro-S C-H bond. T his prochiral selectivity is poorly influenced by the electronic effect of ring substituents, whereas it decreases with the length of the carbon later al chain, in the order: benzyl alcohol > 2-phenylethanol > 3-phenylpropanol . Molecular binding studies showed that the main factor directing the docki ng of the substrate in such a specific orientation in the enzyme active sit e is the interaction between the alcoholic OH group and the residue Glu183. This interaction is likely to drive both the stereochemistry and the regio chemistry of these reactions. A bifurcated hydrogen bond involving the OH g roup, the carboxylate oxygen of Glu183 and the oxoferryl oxygen might also be operating.