Chemical and enzymatic oxidation of 2-aryl-1,3-oxathiolanes: mechanism of the hepatic flavin-containing monooxygenase

• Published in: Journal of the American Chemical Society Vol. 111; no. 13; pp. 4844 - 4852
• Main Authors: CASHMAN, J. R, PROUDFOOT, J, YEN-KUANG HO, CHIN, M. S, OLSEN, L. D
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 1989
• Subjects: 2-aryl-13-oxathiolane; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; liver; Oxidoreductases; Enzyme
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja00195a041

The reaction of NaIO sub(4), H sub(2)O sub(2), and highly purified and microsomal hog and rat liver flavin-containing monooxygenase with 2-aryl-1,3-oxathiolanes was investigated. The rho values determined from Hammett plots for the rate of S-oxygenation are consistent with substantial nucleophilic character for the chemical reaction but this does not preclude radical character in the reaction. For the biotransformation reactions, the data provide evidence for a minor role of cytochrome P-450 in the S-oxygenation of 2-aryl-1,3-oxathiolanes, but the flavin-containing monooxygenase represents by far the major pathway for S-oxide formation. The diastereochemical outcome of the S-oxygenation of 2-aryl-1,3-oxathiolanes was determined and, in general, hog liver flavin-containing monooxygenase demonstrated considerable S-oxygenation stereoselectivity while rat liver flavin-containing monooxygenase (FMO) was markedly less stereoselective. The reactions of 2-aryl-1,3-oxathiolanes with H sub(2)O sub(2) and FMO serve to demonstrate the electronic and stereochemical requirements for S-oxygenation of dialkyl sulfides and provide evidence that rat and hog liver FMO are two different forms of the same enzyme.