Detailed mechanism of the autoxidation of N-hydroxyurea catalyzed by a superoxide dismutase mimic Mn(III) porphyrin: formation of the nitrosylated Mn(II) porphyrin as an intermediate.
The in vitro autoxidation of N-hydroxyurea (HU) is catalyzed by Mn(III)TTEG-2-PyP(5+), a synthetic water soluble Mn(III) porphyrin which is also a potent mimic of the enzyme superoxide dismutase. The detailed mechanism of the reaction is deduced from kinetic studies under basic conditions mostly based on data measured at pH = 11.7 but also including some pH-dependent observations in the pH range 9-13. The major intermediates were identified by UV-vis spectroscopy and electrospray ionization mass spectrometry. The reaction starts with a fast axial coordination of HU to the metal center of Mn(III)TTEG-2-PyP(5+), which is followed by a ligand-to-metal electron transfer to get Mn(II)TTEG-2-PyP(4+) and the free radical derived from HU (HU˙). Nitric oxide (NO) and nitroxyl (HNO) are minor intermediates. The major pathway for the formation of the most significant intermediate, the {MnNO} complex of Mn(II)TTEG-2-PyP(4+), is the reaction of Mn(II)TTEG-2-PyP(4+) with NO. We have confirmed that the autoxidation of the intermediates opens alternative reaction channels, and the process finally yields NO(2)(-) and the initial Mn(III)TTEG-2-PyP(5+). The photochemical release of NO from the {MnNO} intermediate was also studied. Kinetic simulations were performed to validate the deduced rate constants. The investigated reaction has medical implications: the accelerated production of NO and HNO from HU may be utilized for therapeutic purposes.
Department of Inorganic and Analytical Chemistry, University of Debrecen, Debrecen, Hungary H-4010, POB-21.
József
J
Kalmár
Bernadett
B
Biri
Gábor
G
Lente
István
I
Bányai
Ana
A
Budimir
Mladen
M
Biruš
Ines
I
Batinić-Haberle
István
I
Fábián
D040761:Biomimetic Materials / Q000737:chemistry* / Q000378:metabolism; D002384:Catalysis; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry; D004579:Electron Transport; D006863:Hydrogen-Ion Concentration; D006918:Hydroxyurea / Q000737:chemistry*; D007700:Kinetics; D008345:Manganese / Q000737:chemistry*; D009569:Nitric Oxide / Q000737:chemistry; D010084:Oxidation-Reduction; D011166:Porphyrins / Q000737:chemistry*; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism
D056831:Coordination Complexes; D011166:Porphyrins; D009569:Nitric Oxide; D008345:Manganese; D013482:Superoxide Dismutase; D006918:Hydroxyurea