Optimization of reaction parameters for the electrochemical oxidation of lidocaine with a Design of Experiments approach

Gül, Turan; Bischoff, Rainer; Permentier, Hjalmar P.

doi:10.1016/j.electacta.2015.04.160

Cited by 13 publications

(15 citation statements)

References 30 publications

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“…As previously reported, the electrochemical N-dealkylation reaction of lidocaine is completely suppressed at pH values below 0.5 [35]. Unexpectedly, under these strongly acidic conditions aromatic hydroxylation metabolites of lidocaine are produced instead.…”

Section: Aromatic Hydroxylation Reactions Of Lidocaine Under Strong Asupporting

confidence: 71%

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

Gül

Bischoff

Permentier

2017

Electrochimica Acta

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Please cite this article as: Turan Gül, Rainer Bischoff, Hjalmar P.Permentier, Mechanism of aromatic hydroxylation of lidocaine at a Pt electrode under acidic conditions, Electrochimica Acta http://dx. AbstractAromatic 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 3hydroxylidocaine, which is an in vivo metabolite of lidocaine. Experiments in 18 O labelled water indicated that water is the primary source of oxygen, while dissolved molecular oxygen contributes to a minor extent to the hydroxylation reaction. Key words -Drug metabolism -Aromatic hydroxylation -Pt-oxide layer -Electrochemical synthesis -18 O labeled water

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Section: Aromatic Hydroxylation Reactions Of Lidocaine Under Strong Asupporting

confidence: 71%

“…We showed recently that N-dealkylation of lidocaine is favored under basic conditions, while this reaction was completely suppressed at pH values below 0.5 in the presence of trifluoroacetic acid (TFA) [35]. In addition, we observed that aromatic hydroxylation products were readily produced under these conditions.…”

Section: Introductionmentioning

confidence: 90%

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

Gül

Bischoff

Permentier

2017

Electrochimica Acta

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“…Full factorial (FF) designs are most popular strategies such as response surface methodology (RSM), center composite design (CCD) and orthogonal array (OA) Taguchi design of experiment. Detailed information about DOE approach and its various applications may readily be found in the related literatures [18,19].…”

Section: Design Of Experimentsmentioning

confidence: 99%

Optimization of backpropagation neural network-based models in EDM process using particle swarm optimization and simulated annealing algorithms

Saffaran

Moghaddam

Kolahan

2020

J Braz. Soc. Mech. Sci. Eng.

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In the present study, artificial neural network (ANN) along with heuristic algorithms, namely particle swarm optimization (PSO) and simulated annealing (SA), has been employed to carry out the modeling and optimization procedure of electrical discharge machining (EDM) process on AISI2312 hot worked steel parts. Surface roughness (SR), tool wear rate (TWR) and material removal rate (MRR) are the process quality measures considered as process output characteristics. Determination of a process variables (pulse on and off time, current, voltage and duty factor) combination to minimize TWR and SR and maximize MRR independently (as single objective) and also simultaneously (as multi-criteria) optimization is the main objective of this study. The experimental data are gathered using Taguchi L 36 orthogonal array based on design of experiments approach. Next, the output measures are used to develop the ANN model. Furthermore, the architecture of the ANN has been modified using PSO algorithm. At the last step, in order to determine the best set of process output variables values for a desired set of process quality measures, the developed ANN model is embedded into proposed heuristic algorithms (SA and PSO) with which their derived results have been compared. It is evident that the proposed optimization procedure is quite efficient in modeling (with less than 1% error) and optimization (less than 4 and 7 percent error for single-and multiobjective optimizations, respectively) of EDM process variables.

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“…Similar methods have been applied to paracetamol by the same group . Gul and colleagues have further optimised the reaction via a design of experiments approach alongside 18 O‐labelling studies to interrogate the mechanism …”

Section: Preparative Electrosynthesis Of Drug Metabolitesmentioning

confidence: 99%

“…[61] Gul and colleagues have further optimised the reaction via a design of experiments approach alongside 18 Olabelling studies to interrogate the mechanism. [62][63] There is a growing body of examples of preparative electrosynthesis to drug metabolites. Could this ability to late stage functionalise (LSF) drug molecules be taken one step further and used to develop metabolism inspired electrosynthetic reactions with the goal to generate drug molecules and metabolites more generally?…”

Section: Preparative Electrosynthesis Of Drug Metabolitesmentioning

confidence: 99%

Metabolism‐Inspired Electrosynthesis

2019

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Drug metabolism is a critical stage in the development of new chemical entities to understand how the drug will behave in the body and to reveal potential toxic metabolites. In this Review, we discuss how a renaissance in the applications of synthetic electrochemistry can be employed both to identify drug metabolites (and mechanisms) and enable electrosynthetic preparation of drug metabolites for further analysis. Recent advances in electro‐oxidative drug reactions are reviewed together with a perspective on the future use of electrosynthesis to diversify lead stage drug molecules to enable rapid testing of advanced analogues. A focus on the remarkable advances in the last decade with the inclusion of seminal papers for contextual analysis are reviewed.

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Optimization of reaction parameters for the electrochemical oxidation of lidocaine with a Design of Experiments approach

Cited by 13 publications

References 30 publications

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

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

Optimization of backpropagation neural network-based models in EDM process using particle swarm optimization and simulated annealing algorithms

Metabolism‐Inspired Electrosynthesis

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