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

József Kalmár, Bernadett Biri, G. Lente, I. Bányai, Ana Budimir, Mladen Biruš, Ines Batinić-Haberle, I. Fábián

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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 MnIIITTEG-2-PyP5+, which is followed by a ligand-to-metal electron transfer to get MnIITTEG-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 MnIITTEG-2-PyP4+, is the reaction of MnIITTEG-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 MnIIITTEG-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.

Original languageEnglish
Pages (from-to)11875-11884
Number of pages10
JournalDalton Transactions
Volume41
Issue number38
DOIs
Publication statusPublished - Oct 14 2012

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Hydroxyurea
Porphyrins
Nitric Oxide
Metals
Electrospray ionization
Kinetics
Ultraviolet spectroscopy
Superoxide Dismutase
Free Radicals
Mass spectrometry
Rate constants
Ligands
Electrons
Water
Enzymes

ASJC Scopus subject areas

  • Inorganic Chemistry

Cite this

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. / Kalmár, József; Biri, Bernadett; Lente, G.; Bányai, I.; Budimir, Ana; Biruš, Mladen; Batinić-Haberle, Ines; Fábián, I.

In: Dalton Transactions, Vol. 41, No. 38, 14.10.2012, p. 11875-11884.

Research output: Contribution to journalArticle

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AU - Kalmár, József

AU - Biri, Bernadett

AU - Lente, G.

AU - Bányai, I.

AU - Budimir, Ana

AU - Biruš, Mladen

AU - Batinić-Haberle, Ines

AU - Fábián, I.

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