Prochiral selectivity in H(2)O(2)-promoted oxidation of arylalkanols catalysed by chloroperoxidase. The role of the interactions between the OH group and the amino-acid residues in the enzyme active site.
The H(2)O(2)-promoted oxidations of (R)-[alpha-(2)H(1)]-and (S)-[alpha-(2)H(1)]-arylalkanols catalysed by chloroperoxidase (CPO) from Caldariomyces fumago have been investigated. It has been found that with (R)-[alpha-(2)H(1)]-alcohols, the oxidation involves almost exclusively the cleavage of the C-H bond, whereas in the case of the oxidation of (S)-[alpha-(2)H(1)]-alcohols, the C-D bond is preferentially broken. These results clearly indicate that the reactions of corresponding undeuterated arylalkanols are characterized by a high prochiral selectivity, involving the cleavage of the pro-S C-H bond. This prochiral selectivity is poorly influenced by the electronic effect of ring substituents, whereas it decreases with the length of the carbon lateral chain, in the order: benzyl alcohol > 2-phenylethanol > 3-phenylpropanol. Molecular binding studies showed that the main factor directing the docking of the substrate in such a specific orientation in the enzyme active site is the interaction between the alcoholic OH group and the residue Glu183. This interaction is likely to drive both the stereochemistry and the regiochemistry of these reactions. A bifurcated hydrogen bond involving the OH group, the carboxylate oxygen of Glu183 and the oxoferryl oxygen might also be operating.
Baciocchi
E
E
Dipartimento di Chimica, Università La Sapienza, Rome, Italy. baciocchi@caspur.it
Fabbrini
M
M
Lanzalunga
O
O
Manduchi
L
L
Pochetti
G
G
D000596:Amino Acids / Q000737:chemistry; D000840:Anisoles / Q000737:chemistry; D001592:Benzyl Alcohols / Q000737:chemistry; D001665:Binding Sites; D002384:Catalysis; D002711:Chloride Peroxidase / Q000378:metabolism*; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000378:metabolism; D018698:Glutamic Acid / Q000737:chemistry; D006860:Hydrogen Bonding; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007700:Kinetics; D008956:Models, Chemical; D010100:Oxygen / Q000378:metabolism*; D010626:Phenylethyl Alcohol / Q000737:chemistry; D020005:Propanols / Q000737:chemistry; D011485:Protein Binding
D000596:Amino Acids; D000840:Anisoles; D001592:Benzyl Alcohols; D005656:Fungal Proteins; D020005:Propanols; C016655:3-phenylpropanol-1; C028385:4-(trifluoromethyl)benzyl alcohol; D018698:Glutamic Acid; C066943:anisyl alcohol; D006861:Hydrogen Peroxide; D002711:Chloride Peroxidase; D010626:Phenylethyl Alcohol; D010100:Oxygen