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

Abstract

The in vitro autoxidation of N-hydroxyurea (HU) is catalyzed by Mn^IIITTEG-2-PyP⁵⁺, 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^IIITTEG-2-PyP⁵⁺, which is followed by a ligand-to-metal electron transfer to get Mn^IITTEG-2-PyP⁴⁺ 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^IITTEG-2-PyP⁴⁺, is the reaction of Mn^IITTEG-2-PyP⁴⁺ with NO. We have confirmed that the autoxidation of the intermediates opens alternative reaction channels, and the process finally yields NO₂⁻ and the initial Mn^IIITTEG-2-PyP⁵⁺. 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.