Q88349644 Dotaz Zobrazit nápovědu
Cytotoxic properties of radiosensitizers are due to the fact that, in the metabolic pathway, these compounds undergo one-electron reduction to generate radical anions. In this study we focused our interest on the electrochemical transfer of the first electron on radiosensitizer Etanidazole (ETN) and, consequently, on the ETN radical-anion formation in the buffered aqueous media. ETN was electrochemically treated in the broad pH range at various scan rates. Three reduction peaks and one oxidation peak were found. At strong alkaline pH the four-electron reduction peak was separated into one-electron and three-electron reductions. Under these conditions the standard rate constant k(0) for the redox couple ETN-NO(2)+e(-) <--> ETN-NO(2)(*-) was calculated. Moreover, the value of a so called E(7)(1) potential that accounts for the energy necessary to transfer the first electron to an electroactive group at pH=7 in aqueous medium to form a radical anion was also determined. The obtained value of E(7)(1) indicates that lower energy compared to the other possible chemical radiosensitizers is necessary for the system to transfer the first electron to ETN. On the other hand, the necessity of the strong alkaline pH may decrease the ability of ETN to act as hypoxic radiosensitizer in the human body.
- MeSH
- anionty chemie MeSH
- elektrická vodivost MeSH
- elektrochemie MeSH
- etanidazol chemie MeSH
- hypoxie buňky MeSH
- kinetika MeSH
- koncentrace vodíkových iontů MeSH
- radiosenzibilizující látky chemie MeSH
- transport elektronů MeSH
- voda chemie MeSH
- volné radikály chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The reduction of nitroaromatic compound bifenox (methyl 5-(2,4-dichlorophenoxy)-2-nitrobenzoate) was studied in aprotic solvents in the absence or presence of cyclodextrin (CD) molecules of different cavity sizes. ßCD and ?CD form complexes with bifenox in DMSO with the complex formation constants (5 ± 2) × 102 M–1 [ßCD–bifenox] and (3 ± 1) × 102 M–1 [?CD–bifenox], respectively. Bifenox yields a relatively stable anion radical in dimethyl sulfoxide, which is further reduced at more negative potentials by an overall addition of three electrons and four protons to the corresponding phenylhydroxylamine. In the presence of ßCD the first reduction wave of bifenox becomes irreversible, it is shifted towards more positive potentials and the uptake of more than one electron is observed (up to four electrons during the exhaustive electrolysis). The first reduction wave of bifenox is not affected by the addition of glucose confirming that a simple availability of protons from the OH groups is not the main factor in further transformation of anion radical in the presence of ßCD. The complex formation with ßCD facilitates the protonation and additionally protects the molecule from disintegration into 2,4-dichlorophenol. A yield of 2,4-dichlorophenol decreases in the order ßCD, ?CD and ?CD, respectively.
Electrochemical transfer of the first electron to cytotoxic radiosensitizer etanidazole (ETN) and ETN radical anion formation in the alkaline buffered aqueous solution were studied by means of electrochemical impedance spectroscopy (EIS). The heterogeneous electron transfer rate constant for the first reduction of ETN (radical anion production), k0, was calculated. The value of k0 from EIS measurements and the previously obtained value of so-called E71 potential indicate that ETN, compared with other possible chemical radiosensitizers, requires lower energy to accept the first electron during the metabolic pathway. However, the necessity of the alkaline pH may decrease the ability of ETN to act as hypoxic radiosensitizer in the human body.
This contribution pays a tribute to a humble and talented physical chemist, Professor Heyrovsky, who was for his achievements awarded, as the only Czechoslovak scientist, the Nobel Prize in chemistry on 10th December, 1959.
