Kinetics and Mechanism of Oxidation of N-acetyl-d-penicillamine in Acidified Iodate and Aqueous Iodine

Abstract

The oxidation of the biologically-active thiol, N-acetyl-d-penicillamine (NDPen) by acidified iodate and aqueous iodine has been studied. The stoichiometry of the reaction is 1:1 in which the thiol (RSH) is oxidized to its sulfonic acid (RSO₃H) without cleavage of the C-S bond. In excess acidified iodate the reaction displayed a short induction period, followed by formation of aqueous iodine. Overall stoichiometry in excess iodate was 6:5: 6 IO₃ –+5RSH+6H⁺→5 RSO₃H+3I₂(aq)+3H₂O. The direct reaction of aqueous iodine and was relatively fast, over within 100 ms and had a stoichiometry of 1:3: 3 I₂(aq) + RSH+3H₂O →RSO₃H+6 I^– + 6 H⁺. The reaction is essentially diffusion-controlled and our stopped-flow with a mixing time limitation of 1.00 ms could only catch the reaction of the last iodine molecule. This reaction is, however, strongly inhibited by the product of reaction, I^– . This is due to the formation of the relatively inert triiodide anion: I2(aq)+I^–→I₃ –. Mass spectrometry results showed that the reaction proceeds through the sulfinic acid with negligible stabilization of the sulfenic acid. In excess of reductant, the dimeric species is the favoured product due to a rapid condensation-type reaction between the electrophilic unstable sulfenic acid and unreacted thiol.

Keywords: Biological thiols, bioactivation, oxidations, oxyhalogen chemistry.