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 degrees C in aqueous 0.1 mol/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 beta-613 ([FeL3(3-)][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 FeL3(3-) dominate under physiological pH 7.4. Comparison of iron(III) species distribution in a competitive two-ligand entacapone-catechol system reveals that the complexation of entacepone is favored at high and low dilution.
Orama
M
M
Department of Chemistry, University of Helsinki, Espoo, Finland.
Tilus
P
P
Taskinen
J
J
Lotta
T
T
D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000737:chemistry*; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007502:Iron Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry*; D009570:Nitriles; D011199:Potentiometry
D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D007502:Iron Chelating Agents; D009570:Nitriles; C071192:entacapone