Surface-modified electrodes in the mimicry of oxidative drug metabolism

Yuan, Tao; Permentier, Hjalmar P.; Bischoff, Rainer

doi:10.1016/j.trac.2015.01.017

Cited by 15 publications

(11 citation statements)

References 66 publications

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“…[2] Drug metabolites are valuable chemicals and play an integral part in the development of safe and effective pharmaceuticals, since they are critical for ADME (adsorption, distribution, metabolism, and excretion) studies during the early stages of drug discovery and development. [3,4] The synthesis of metabolites on a preparative scale is important to perform toxicology, pharmacokinetics, pharmacodynamics, and bioavailability studies. [5] Moreover, the elucidation of chemical structures and safety testing of metabolites are mandated by governmental regulators such as the U.S. Food and Drug Administration (FDA).…”

Section: Introductionmentioning

confidence: 99%

“…The chemical modifications of drug metabolism are mainly carried out by members of the Cytochrome P450s (CYP) enzyme family in the human liver [2] . Drug metabolites are valuable chemicals and play an integral part in the development of safe and effective pharmaceuticals, since they are critical for ADME (adsorption, distribution, metabolism, and excretion) studies during the early stages of drug discovery and development [3,4] . The synthesis of metabolites on a preparative scale is important to perform toxicology, pharmacokinetics, pharmacodynamics, and bioavailability studies [5] .…”

Section: Introductionmentioning

confidence: 99%

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Nanoporous Gold Catalyst for the Oxidative N‐Dealkylation of Drug Molecules: A Method for Synthesis of N‐Dealkylated Metabolites

et al. 2022

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A novel method for the selective catalytic N‐dealkylation of drug molecules on a nanoporous gold (NPG) catalyst producing valuable N‐dealkylated metabolites and intermediates is described. Drug metabolites are important chemical entities at every stage of drug discovery and development, from exploratory discovery to clinical development, providing the safety profiles and the ADME (adsorption, distribution, metabolism, and elimination) of new drug candidates. Synthesis was carried out in aqueous solution at 80 °C using air (oxygen source) as oxidant, in single step with good isolated yields. Different examples examined in this study showed that aerobic catalytic N‐dealkylation of drug molecules on NPG has a broad scope supporting N‐deethylation, N‐deisopropylation and N‐demethylation, converting either 3° amines to 2° amines, or 2° amines to 1° amines.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nanoporous Gold Catalyst for the Oxidative N‐Dealkylation of Drug Molecules: A Method for Synthesis of N‐Dealkylated Metabolites

et al. 2022

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“…While biotic transformation of diPAPs was investigated in previous studies, − ,− little is known about abiotic transformation pathways in the environment. Electrochemical oxidation (EO) was successfully used to simulate biochemical transformation processes , and oxidative processes in the environment. , EO can also be used to generate environmental transformation products (TPs) and to study environmental reactions with • OH. The advantage of EO in contrast to microbial degradation experiments is the easy and accurate control of reaction parameters and the fast reaction kinetics, allowing rapid generation of relevant information.…”

Section: Introductionmentioning

confidence: 99%

Electrochemical Oxidation of 6:2 Polyfluoroalkyl Phosphate Diester—Simulation of Transformation Pathways and Reaction Kinetics with Hydroxyl Radicals

Zweigle

Bugsel

Schmitt

et al. 2021

Environ. Sci. Technol.

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Polyfluoroalkyl phosphate diesters (diPAPs) are widely used for paper and cardboard impregnation and discharged via waste streams from production processes and consumer products. To improve the knowledge about the environmental fate of diPAPs, electrochemical oxidation (EO) was used to characterize the transformation pathways and reaction kinetics. 6:2 diPAP was transformed electrochemically to perfluorocarboxylic acids (C 5 −C 7 PFCAs) and two intermediates (6:2 fluorotelomer carboxylic acid, FTCA, and 6:2 fluorotelomer unsaturated carboxylic acid, FTUCA). EO of potential intermediates 6:2 monoPAP and 6:2 fluorotelomer alcohol (FTOH) showed similar transformation products but with different ratios. We show that 6:2 diPAP is initiated by OH radical ( • OH) reactions, as evidenced by the measured steady-state concentrations of • OH with the probe molecule terephthalic acid, quenching experiments, and pH dependency of the reaction. PFHpA was the main product of 6:2 diPAP oxidation, and it was formed in a pseudo-first-order reaction for which a bimolecular rate constant was estimated to be • k OH,diPAP form PFHpA = 9.4(±1.4) × 10 7 M −1 s −1 by an initial rate approach. This can be utilized to estimate the environmental half-life of 6:2 diPAP for the reaction with • OH and the formation kinetics of persistent PFCAs.

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“…The first step in the metabolism of drugs in vivo is first pass hepatic oxidation by Cytochrome P450 oxidase liver enzymes, which contain an Fe porphyrin. Oxidative methodologies which are able to mimic drug metabolism are thus in high demand [246,247].…”

Section: − O Bond Formationmentioning

confidence: 99%

Pushing the boundaries of C–H bond functionalization chemistry using flow technology

2020

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C-H functionalization chemistry is one of the most vibrant research areas within synthetic organic chemistry. While most researchers focus on the development of small-scale batch-type transformations, more recently such transformations have been carried out in flow reactors to explore new chemical space, to boost reactivity or to enable scalability of this important reaction class. Herein, an up-to-date overview of C-H bond functionalization reactions carried out in continuous-flow microreactors is presented. A comprehensive overview of reactions which establish the formal conversion of a C-H bond into carbon-carbon or carbonheteroatom bonds is provided; this includes metal-assisted C-H bond cleavages, hydrogen atom transfer reactions and C-H bond functionalizations which involve an S E-type process to aromatic or olefinic systems. Particular focus is devoted to showcase the advantages of flow processing to enhance C-H bond functionalization chemistry. Consequently, it is our hope that this review will serve as a guide to inspire researchers to push the boundaries of C-H functionalization chemistry using flow technology.

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Surface-modified electrodes in the mimicry of oxidative drug metabolism

Cited by 15 publications

References 66 publications

Nanoporous Gold Catalyst for the Oxidative N‐Dealkylation of Drug Molecules: A Method for Synthesis of N‐Dealkylated Metabolites

Nanoporous Gold Catalyst for the Oxidative N‐Dealkylation of Drug Molecules: A Method for Synthesis of N‐Dealkylated Metabolites

Electrochemical Oxidation of 6:2 Polyfluoroalkyl Phosphate Diester—Simulation of Transformation Pathways and Reaction Kinetics with Hydroxyl Radicals

Pushing the boundaries of C–H bond functionalization chemistry using flow technology

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