title: Tyrosinase-catalyzed oxidation of fluorophenols.
abstract: The activity of the type 3 copper enzyme tyrosinase toward 2-, 3-, and 4-fluorophenol was studied by kinetic methods and (1)H and (19)F NMR spectroscopy. Whereas 3- and 4-fluorophenol react with tyrosinase to give products that undergo a rapid polymerization process, 2-fluorophenol is not reactive and actually acts as a competitive inhibitor in the enzymatic oxidation of 3,4-dihydroxyphenylalanine (L-dopa). The tyrosinase-mediated polymerization of 3- and 4-fluorophenols has been studied in detail. It proceeds through a phenolic coupling pathway in which the common reactive fluoroquinone, produced stereospecifically by tyrosinase, eliminates an inorganic fluorine ion. The enzymatic reaction studied as a function of substrate concentration shows a prominent lag that is completely depleted in the presence of L-dopa. The kinetic parameters of the reactions can be correlated to the electronic and steric effects of the fluorine substituent position. Whereas the fluorine electron withdrawing effect appears to control the binding of the substrates (K(m) for 3- and 4-fluorophenols and K(I) for 2-fluorophenol), the k(cat) parameters do not follow the expected trend, indicating that in the transition state some additional steric effect rules the reactivity.
authors.affiliation: Dipartimento di Chimica Generale, Università di Pavia, Via Taramelli 12, 27100 Pavia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Battaini
authors.forename: Enrico
authors.initials: E
authors.lastname: Monzani
authors.forename: Luigi
authors.initials: L
authors.lastname: Casella
authors.forename: Emanuela
authors.initials: E
authors.lastname: Lonardi
authors.forename: Armand W J W
authors.initials: AW
authors.lastname: Tepper
authors.forename: Gerard W
authors.initials: GW
authors.lastname: Canters
authors.forename: Luigi
authors.initials: L
authors.lastname: Bubacco
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D001205:Ascorbic Acid / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D003300:Copper / Q000378:metabolism; D017611:Fluorine Compounds / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D010636:Phenols / Q000737:chemistry* / Q000378:metabolism; D013303:Streptomyces antibioticus / Q000201:enzymology; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001426:Bacterial Proteins; D017611:Fluorine Compounds; D010636:Phenols; D015262:Xenobiotics; D003300:Copper; D014442:Monophenol Monooxygenase; D001205:Ascorbic Acid