Publication

Nanostructured gold: applications in the study of drug metabolism

Yuan, T., 2017, [Groningen]: University of Groningen. 119 p.

Research output: ThesisThesis fully internal (DIV)

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  • Tao Yuan
The aim of this thesis is to improve the yield and the selectivity of specific drug metabolites, with particular emphasis on N-dealkylation metabolites in this study. Electrochemistry is used to produce drug metabolites under precise potential control. However, the selectivity and yield of drug metabolites synthesized by direct electrochemistry are often quite low, making the following separation processes laborious and product upscaling difficult.
Electrodes modified with enzymes of the Cytochrome P450 (CYP450) family in humans provide a possible way to improve the selectivity by mimicking oxidative drug metabolism as executed by CYP450 in vivo. We modified a gold disk electrode with the metalloporphyrin hemin, the active site constituent of CYP450, for an in-situ surface enhanced Raman scattering spectroelectrochemical (SERS SEC) characterization.
The yield of the N-dealkylation drug metabolites is highly dependent on the surface area of the working electrode. Thus, we prepared nanoporous gold (NPG) electrodes. It turned out that the NPG can very efficiently catalyze the N-dealkylation reaction without applying any potential on the electrode. Moreover, the selectivity of N-dealkylation is highly improved on the NPG compared to reported electrochemical methods.
Following up on the work of in-batch NPG catalysis described above, a continuous-flow reactor by integration of NPG was designed for the catalytic N-dealkylation of lidocaine, metoprolol and atropine on NPG by flow chemistry. Such a continuous flow system has a fast response and is easy to handle, and is promising for upscaling N-dealkylation reactions for the synthesis of drug metabolites.
Translated title of the contributionGoud-nanostructuren: toepassingen in de studie van drug metabolisme
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
Award date2-Jun-2017
Place of Publication[Groningen]
Publisher
Print ISBNs978-90-367-9782-5
Electronic ISBNs978-90-367-9781-8
Publication statusPublished - 2017

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