| Clioquinol (CQ) is a halogenated derivative of8-hydroxyquinoline that was widelyused in medical and health fields. It was initially used as an antibiotic for the treatment ofdiarrhea and skin infection. Recently, CQ has received new attention due to its ability todissolve copper from amyloid-β peptide aggregates associated with Alzheimer’s disease.Unfortunately, CQ has been withdrawn from the market as an oral agent in the early1970sbecause of its association with subacute myelo-optic neuropathy. The toxicity mechanismis not fully understood. Some research have found that the mechanism of many drugs arerelated to its product produced by oxidation.Monitoring of intermediates and unstable products is very important for clarifyingcomplex electrochemical reaction pathways. A combination of thin-layer spectral andelectrophoretic electrochemistry, both based on fast thin-layer electrolysis, has beendeveloped to monitor the intermediates of electro-oxidation of clioquinol in acidic,physiological and alkaline buffer media. Two thin-layer electrochemical cells werefabricated and coupled with a UV-vis spectrometer and an electrophoresis apparatus,respectively.In this thesis, the electroxidation mechanisms of cliquinol was studied at carbon pasteand graphite sheet working electrode using electrochemical; in situ UV-visspectroelectrochemical methods and a device of chip-type thin-layer electrolytic cellcoupled with high-performance capillary electrophoresis. Double-potential thin-layerUV–vis spectroelectrochemistry, double-wavelength thin-layer cyclic voltabsorptometryand thin-layer electrophoretic electrochemistry provided mutually-supporting informationon the redox pathway of clioquinol. The oxidation products of CQ at three pH valueswere separated by thin-layer electrophoretic electrochemistry, based on the chip thin-layerelectrolysis cell with a capillary channel and a BGE reservoir. A phenoxy radical wasinitially formed at the anodic peak A1through one-electron one-proton oxidation of CQ,followed by an addition reaction with OH–to form a semiquinone anion radical. Thisaddition reaction was so fast that no cathodic voltammetric peak was observed for thereduction of the phenoxy radical. The semiquinone intermediate underwent adisproportionation reaction to generate CQ and a p-quinone intermediate. Thedisproportionation reaction was relatively slow at pH10.4. The intermediate3was furtherhydrolyzed to generate quinolinic acid at pH1.8, or3-hydroxy picolinic acid at pH7.4 and10.4. The final soluble products of CQ are pH-dependent but irrelevant to whether theoxidation reaction is electrochemical or chemical in nature.This study provides a significant example of the combination of in situ and onlinethin-layer techniques for the purpose of detecting the unstable intermediates and thereforeenriching the knowledge about the electro-oxidation pathways of CQ in different pHbuffers. |
