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Nitrosyl iron complex with N-ethylthiourea ligands: reactions with hemoglobin

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Abstract

Reactions between the nitrosyl iron complex with N-ethylthiourea ligands {Fe[SC(NH2)-(NHEt)]2(NO)2}+Cl−•{Fe[SC(NH2)(NHEt)]Cl(NO)2}0 (complex 1) and hemoglobin under aerobic and anaerobic conditions were studied. It was found that the protein stabilizes the complex, making it a more prolonged nitric oxide (NO) donor, namely, the rate of NO generation in the systems with oxy- and deoxyhemoglobin (determined from the kinetics of accumulation of methemoglobin and nitrosylated hemoglobin) is lower than in an aqueous buffer solution. According to EPR spectroscopy data, rotation of paramagnetic centers in the reaction mixture is hindered due to the binding of complex 1 to the protein molecule. In the system with oxyhemoglobin, the effect of oxygen on the decomposition of complex 1 was also taken into account. According to quantum chemical calculations and EPR spectroscopy data, both the cationic and neutral fragments of the title complex decompose in aqueous solution in the presence of oxygen. The decomposition pathways are proposed. The observed effects provide a prolonged action of complex 1 as a NO donor, which can increase its potential pharmacological efficacy.

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Authors and Affiliations

  1. Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 1 prosp. Akad. Semenova, 142432, Chernogolovka, Moscow Region, Russian Federation

    V. O. Novikova, N. S. Emel’yanova, A. V. Kulikov, A. V. Marina, O. V. Pokidova & N. A. Sanina

  2. Faculty of Fundamental Physical and Chemical Engineering, Lomonosov Moscow State University, Build. 51, 1 Leninskie Gory, 119991, Moscow, Russian Federation

    N. S. Emel’yanova, A. V. Marina & N. A. Sanina

  3. Scientific and Educational Center “Medical Chemistry” of Moscow State Regional University, 24 ul. Very Voloshinoy, 141014, Mytishchi, Moscow Region, Russian Federation

    N. A. Sanina

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  1. V. O. Novikova
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  2. N. S. Emel’yanova
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Correspondence to O. V. Pokidova.

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Dedicated to Academician of the Russian Academy of Sciences I. P. Beletskaya on the occasion of her anniversary.

This work was financially supported by the Russian Science Foundation (Project No. 20-73-00316, studies of structural transformations of the complex in aerobic protein solution) and within the framework of the State Assignment (Reg. No. AAAA-A19-119071890015-6, synthesis of complex).

The animal study protocols met the Institutional Animal Ethics Regulations and the Russian Federation laws and international legislation.

The authors declare no competing interests.

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, Vol. 72, No. 4, pp. 902–911, April, 2023.

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Novikova, V.O., Emel’yanova, N.S., Kulikov, A.V. et al. Nitrosyl iron complex with N-ethylthiourea ligands: reactions with hemoglobin. Russ Chem Bull 72, 902–911 (2023). https://doi.org/10.1007/s11172-023-3853-8

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  • DOI: https://doi.org/10.1007/s11172-023-3853-8

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