Adduct formation of electrochemically generated reactive intermediates with biomolecules

Comparison of in Silico, Electrochemical, in Vitro and in Vivo Metabolism of a Homologous Series of (Radio)fluorinated σ1 Receptor Ligands Designed for Positron Emission Tomography

“…The CYP‐catalyzed oxidative biotransformation of compounds 1 – 4 can also be simulated by means of electrochemical oxidation. Subsequent mass spectrometric detection and the absence of biological matrices allow the identification of reactive and short‐lived species such as radical cations as well as to evaluate their binding tendency toward selected biomolecules . To investigate the oxidative biotransformation of compounds 1 – 4 electrochemically, a potential ramp was applied to the electrochemical cell and the detected mass spectra were plotted depending on the applied oxidation potential.…”

“…Subsequent mass spectrometric detection and the absence of biological matrices allow the identification of reactive and short-lived speciess uch as radical cations as well as to evaluatet heir binding tendency toward selected biomolecules. [40][41][42][43][44] To investigate the oxidative biotransformation of compounds 1-4 electrochemically,apotential ramp was applied to the electrochemical cell and the detected mass spectra were plottedd epending on the appliedo xidation potential. The obtained mass voltammograms allow an easy identification of possible biotransformation products, since electrochemically generatedo xidation products typically show increasings ignal intensities during the potential ramp, while the signal intensity of the starting compound is decreasing.…”

Electrochemical Aspects of Mass Spectrometry: Atmospheric Pressure Ionization and Ambient Ionization for Bioanalysis

“…Despite the promise of EC‐MS to model metabolic pathways, not all biological reactions can be mimicked. In one case, cytochrome P450‐catalyzed oxidations were studied and although EC‐MS successfully modeled one‐electron oxidations, those reactions which proceed via direct hydrogen atom abstraction were not accurate mimics of the cytochrome P450 system, since the oxidation potentials of those reactions were below the oxidation potential of water …”

“…[125] Electrolysis efficiencies can be as high as 100 % (for 20 pmol reserpine), even at sufficiently high flow rates (800 mL/min) for porous flowthrough cells, due to increased mass transport compared to traditional tubular flow-through cells. [126] Despite the promise of EC-MS to model metabolic pathways, [127][128][129] not all biological reactions can be mimicked. In one case, cytochrome P450-catalyzed oxidations were studied [127] and although EC-MS successfully modeled one-electron oxidations, those reactions which proceed via direct hydrogen atom abstraction were not accurate mimics of the cytochrome P450 system, since the oxidation potentials of those reactions were below the oxidation potential of water.…”

Metabolism‐Inspired Electrosynthesis

“…However, Table highlights the power of electrosynthesis to selectively prepare new functionality on drug molecules, an example of late stage functionalisation on complex structures. Furthermore, the reactive nature of these phase I‐like metabolites, readily allows for trapping via conjugation, for instance with glutathione (GSH), allowing the mimicry of phase II metabolic profiles …”