engleski

Electrochemical properties of iron(iii) complex with antitumor drug hydroxyurea

Hydroxyurea has been extensively used in medical practice for treating a number of cancers, especially chronic myelogenous leukaemia, and sickle cell diseases. Hydroxyurea inhibits ribonucleotide reductase, which catalyses the reduction of ribonucleotides to the corresponding deoxyribonucleotides required for DNA synthesis. Protein R2, a small subunit of ribonucleotide reductase, contains a dinuclear  -oxo-bridged Fe(III) centre and a tyrosyl free radical essential for activity. The precise mechanism of hydroxyurea action is still not completely clear. An investigation of the electron transfer processes in hydroxyurea complexes with Fe(III) may provide a further insight into the mode of hydroxyurea’ s action since iron(III) in the active site of the enzyme participates in the redox reactions. The redox behaviour of the iron(III) complex with hydroxyurea was studied using cyclic and differential-pulse voltammetry. The redox potential of the complex was shifted to less positive values only by 0.1 V compared to the solvated iron(III) ion, indicating a low stability constant for investigated complex. The complex underwent a one-electron reduction, followed by an irreversible chemical reaction (EC mechanism) in which a ligand was released. In addition, it was found that the redox reaction occurred between hydroxyurea and iron(III) in solution. Differential-pulse voltammetry revealed an increase in the concentration of the generated iron(II) species. Electron paramagnetic resonance (EPR) studies of the oxidative degradation of hydroxyurea confirmed the one-electron transfer from hydroxyurea to iron(III) and formation of the radical species H2N-CO-NHO∙ . The observed redox properties indicate that hydroxyurea may interfere with electron transfer processes in biological systems after binding to iron-containing enzymes and that it is able to directly affect the iron centre of ribonucleotide reductase.

Hydroxyurea; iron(III) complex; cyclic voltammetry; differential-pulse voltammetry

nije evidentirano