Mechanism of aromatic hydroxylation of lidocaine at a Pt electrode under acidic conditions

Aromatic hydroxylation reactions, which are mainly catalyzed by cytochrome P450 (CYP) enzymes in vivo, are some of the most important reactions of Phase I metabolism, because insertion of a hydroxyl group into a lipophilic drug compound increases its hydrophilicity and prepares it for subsequent Pha...

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Bibliographic Details
Published in:Electrochimica acta 2017-01, Vol.224, p.636-641
Main Authors: Gul, Turan, Bischoff, Rainer, Permentier, Hjalmar P.
Format: Article
Language:English
Subjects:
18O labeled water
Aromatic hydroxylation
Chemical reactions
Conjugation
Dealkylation
Drug metabolism
Electrochemical oxidation
Electrochemical synthesis
Electrodes
Enzymes
Excretion
Hydroxylation
Metabolism
Metabolites
Molecular structure
Oxygen
Pharmaceuticals
Platinum
Pt-oxide layer
Studies
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Summary:Aromatic hydroxylation reactions, which are mainly catalyzed by cytochrome P450 (CYP) enzymes in vivo, are some of the most important reactions of Phase I metabolism, because insertion of a hydroxyl group into a lipophilic drug compound increases its hydrophilicity and prepares it for subsequent Phase II metabolic conjugation reactions as a prerequisite to excretion. Aromatic hydroxylation metabolites of pharmaceuticals may be obtained through various synthetic and enzymatic methods Electrochemical oxidation is an alternative with advantages in terms of mild reaction conditions and less hazardous chemicals. In the present study, we report that aromatic hydroxylation metabolites of lidocaine can be readily obtained electrochemically under aqueous acidic conditions at platinum electrodes. Our results show that the dominant N-dealkylation reaction can be suppressed by decreasing the solution pH below 0.5 resulting in selective 3-hydroxylidocaine, which is an in vivo metabolite of lidocaine. Experiments in 18O labelled water indicated that water is the primary source of oxygen, while dissolved molecular oxygen contributes to a minor extent to the hydroxylation reaction.
ISSN:0013-4686
1873-3859
DOI:10.1016/j.electacta.2016.12.089