Studies on the oxidative degradation of paracetamol by a μ-oxo-diiron(III) complex

Abstract

In higher organisms, metalloenzymes like cytochrome P450, containing a Fe(III) metal center, play an active role in metabolism of paracetamol (APAP). Here, we have chosen a mimicking μ-oxo-diiron complex, [Fe(III)2(μ-O)(phen)4(H2O)2]4+(1, phen = 1,10-phenanthroline), to study spectrophotometrically the kinetics of the redox interactions with APAP. In acidic buffer media (pH = 3.4–5.1), APAP quantitatively reduces 1 following first-order reaction kinetics. Each molecule of 1 accepts two electrons from APAP and is reduced to ferroin [Fe(phen)3]2+. On oxidation, APAP produces N-acetyl-p-benzoquinone imine (NAPQI), which on hydrolysis results in a mixture of benzoquinone, quinone oxime, acetamide, and acetic acid. In reaction media due to successive deprotonations, 1 exists in equilibrium with the species [Fe(III)2(μ-O)(phen)4(H2O)(OH)]3+(1a) and [Fe(III)2(μ-O)(phen)4(OH)2]2+(1b) (pKa= 3.71 and 5.28, respectively). The kinetic analyses suggest for an unusual reactivity order as 1 < 1a ≫ 1b. The mechanistic possibilities suggest that although 1 is reduced by concerted electron transfer (ET) – proton transfer (PT) mechanism, 1a and 1b may be reduced by a concerted PT–ET mechanism where a slow proton-abstraction step is followed by a rapid ET process. It seems that the initial activation of the bridging μ-oxo group by a proton-abstraction results in the higher reactivity of 1a.