화학공학소재연구정보센터
Journal of Physical Chemistry A, Vol.115, No.14, 3022-3028, 2011
One-Electron Oxidation of Acetohydroxamic Acid: The Intermediacy of Nitroxyl and Peroxynitrite
The pharmacological effects of hydroxamate derivatives have been attributed not only to metal chelation or enzyme inhibition but also to their ability to serve as nitroxyl (HNO/NO-) and nitric oxide (NO) donors. However, the mechanism underlying the formation of these reactive nitrogen species is not clear and requires further elucidation. In the present study, one-electron oxidation of acetohydroxamic acid (aceto-HX) by (OH)-O-center dot, N-center dot(3), (NO2)-N-center dot, CO3 center dot-, and O-2(center dot-) radicals was investigated using pulse radiolysis. It is demonstrated that only (OH)-O-center dot, N-center dot(3), and CO3 center dot- radicals attack effectively and selectively the deprotonated form of the hydroxamate moiety, yielding the respective transient nitroxide radical. This nitroxide radical is a weak acid (CH3C(O)NHO center dot, pK(a) = 9.1), which decays via a pH-dependent second-order reaction, 2k(2CH(3)C(O)NO center dot-) = (5.6 +/- 0.4) x 10(7) M-1 s(-1) (I = 0.002 M), 2k(CH3C(O)NO center dot- + CH3C(O)NHO center dot) = (8.3 +/- 0.5) x 10(8) M-1 s(-1)), and 2k(2CH(3)C(O)NHO center dot) = (8.7 +/- 1.3) x 10(7) M-1 s(-1). The second-order decomposition of the nitroxide yields transient species, one of which decomposes via a first-order reaction whose rate increases linearly upon increasing [CH3C(0)NHO] or [OH]. One-electron oxidation of aceto-HX under anoxia does not give rise to nitrite even after exposure to 02, indicating that NO is not formed during the decomposition of the nitroxide radical. The presence of oxidants such as Tempol or O-2 during CH3C(O)NO center dot-decomposition had no effect on the reaction kinetics. Nevertheless, in the presence of Temopl, which does not react with NO but does with HNO, the formation of the hydroxylamine Tempol-H was observed. In the presence of O-2, about 60% of CH3C(O)NO center dot- yields ONOO-, indicating that 30% NO- is formed in this system. It is concluded that under pulse radiolysis conditions, the transient nitroxide radicals derived from one-electron oxidation of aceto-HX decompose bimoleculary via a complex mechanism forming nitroxyl rather than NO.