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 1H and 19F 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 (Km for 3- and 4-fluorophenols
and KI for 2-fluorophenol), the kcat parameters do
not follow the expected trend, indicating that in the
transition state some additional steric effect rules the
reactivity.
Tyrosinases (