EPR studies on the oxidation of hydroxyurea to paramagnetic compounds by oxyhemoglobin

N. Hydroxyurea forms methemoglobin from oxyhemoglobin with concomitant formation of the aminocarbonylaminooxyl radical H2N-CO-NHO., as detected with electron paramagnetic resonance spectroscopy (EPR). This radical could be detected for several hours in a low steady-state concentration. Approximately 1 hr after the reaction had been started, the EPR spectra of two additional paramagnetic intermediates could be detected at low temperature (77 degrees K), a low-spin ferric methemoglobin complex with hydroxyurea (MetHb-NHOH-CO-NH2) and the hemoglobin-nitric oxide adduct (Hb2(+)-NO). The intensities of their EPR spectra increased steadily over the range of more than 64 hr. The low-spin ferric methemoglobin complex was immediately formed when hydroxyurea was dissolved in a methemoglobin whereas the nitric oxide complex was possibly an oxidation product of the MetHb-hydroxyurea adduct. Its oxidative degradation is known to lead to the very toxic compounds nitric oxide and nitrogen dioxide which can therefore contribute to the toxic action of hydroxyurea.