Iron(III)-Chelating Properties of the Novel Catechol O-Methyltransferase Inhibitor Entacapone in Aqueous Solution

The iron(III) complex formation of entacapone, a novel catechol O-methyltransferase (CoMT) inhibitor, has been studied at 25°C in aqueous 0.1mol/L NaCl solution by using the electromotive force titration method. Entacapone functions as a bidentate ligand chelating through the catecholate oxygen atoms and forms stable iron(III) complexes with the formation constant of a tris complex: log ß-613 ([FeL33־][H]6+/ [Fe3+][H2L]3)=-6.9±0.1. Distribution curves show that entacapone is highly effective for iron (III) in moderately dilute solution (10—3 mol/L) whereas in very dilute solution (10-6 mol/L) the iron hydroxo complexes together with FeL33— dominate under physiological pH7.4. Comparison of iron (III) species distribution in a competitive two-ligand entacapone- catechol system reveals that the complexation of entacapone is favored at high and low dilution.