Tyrosinase-catalyzed oxidation of fluorophenols.
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.
Battaini
Giuseppe
G
Dipartimento di Chimica Generale, Università di Pavia, Via Taramelli 12, 27100 Pavia, Italy.
Monzani
Enrico
E
Casella
Luigi
L
Lonardi
Emanuela
E
Tepper
Armand W J W
AW
Canters
Gerard W
GW
Bubacco
Luigi
L
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
D000975:Antioxidants; D001426:Bacterial Proteins; D017611:Fluorine Compounds; D010636:Phenols; D015262:Xenobiotics; D003300:Copper; D014442:Monophenol Monooxygenase; D001205:Ascorbic Acid