title: Electrocatalytic oxidation of hydrogen peroxide on a platinum electrode in the imitation of oxidative drug metabolism of lidocaine.
abstract: Electrochemistry in combination with mass spectrometry has shown promise as a versatile technique not only in the analytical assessment of oxidative drug metabolism, but also for small-scale synthesis of drug metabolites. However, electrochemistry is generally limited to reactions initiated by direct electron transfer. In the case of substituted-aromatic compounds, oxidation proceeds through a Wheland-type intermediate where resonance stabilization of the positive charge determines the regioselectivity of the anodic substitution reaction, and hence limits the extent of generating drug metabolites in comparison with in vivo oxygen insertion reactions. In this study, we show that the electrocatalytic oxidation of hydrogen peroxide on a platinum electrode generates reactive oxygen species, presumably surface-bound platinum-oxo species, which are capable of oxygen insertion reactions in analogy to oxo-ferryl radical cations in the active site of Cytochrome P450. Electrochemical oxidation of lidocaine at constant potential in the presence of hydrogen peroxide produces both 3- and 4-hydroxylidocaine, suggesting reaction via an arene oxide rather than a Wheland-type intermediate. No benzylic hydroxylation was observed, thus freely diffusing radicals do not appear to be present. The results of the present study extend the possibilities of electrochemical imitation of oxidative drug metabolism to oxygen insertion reactions.
authors.affiliation: Analytical Biochemistry and Mass Spectrometry Core Facility, Department of Pharmacy, University of Groningen, The Netherlands.
authors.forename: Eslam
authors.initials: E
authors.lastname: Nouri-Nigjeh
authors.forename: Andries P
authors.initials: AP
authors.lastname: Bruins
authors.forename: Rainer
authors.initials: R
authors.lastname: Bischoff
authors.forename: Hjalmar P
authors.initials: HP
authors.lastname: Permentier
mesh_terms: D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D055664:Electrochemical Techniques; D004566:Electrodes; D006861:Hydrogen Peroxide / Q000737:chemistry*; D006900:Hydroxylation; D008012:Lidocaine / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D010984:Platinum / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D010984:Platinum; D003577:Cytochrome P-450 Enzyme System; D008012:Lidocaine; D006861:Hydrogen Peroxide