Kinetic Modeling of the Process of the Interaction of Nitric Oxide Donors with Erythrocytes
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TICS AND MECHANISM OF CHEMICAL REACTIONS, CATALYSIS
Kinetic Modeling of the Process of the Interaction of Nitric Oxide Donors with Erythrocytes B. L. Psikhaa, *, N. I. Nesheva, E. M. Sokolovaa, and N. A. Saninaa aInstitute
of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka, Moscow oblast, 142432 Russia *e-mail: [email protected] Received April 24, 2019; revised September 9, 2019; accepted December 20, 2019
Abstract—The mechanism of the interaction of six sulfur-nitrosyl iron complexes capable of releasing nitric oxide as a result of the spontaneous hydrolytic decomposition with a erythrocyte suspension is studied. A kinetic model of the process, which includes reactions of the NO released from the complex into the solution, the NO interaction with oxyhemoglobin within the erythrocyte and dissolved oxygen, and the adsorption of complexes on the surface of erythrocytes, is proposed. The values of the kinetic parameters are determined. The developed model quantitatively describes the experimental data on the accumulation of methemoglobin (the product of the interaction of oxyhemoglobin with nitric oxide) obtained at different concentrations of the studied complexes and erythrocytes in the system. Keywords: sulfur-nitrosyl iron complexes, erythrocytes, nitric oxide, hemoglobin, reaction mechanism, kinetic modeling DOI: 10.1134/S1990793120040107
INTRODUCTION The discovery of the role of nitric oxide as a signaling molecule regulating many physiological processes in the organism and designated simultaneously the pharmacological potential of the chemical compounds that are able to decompose with the release of nitric oxide molecules (nitric oxide donors) [1–3]. In particular, binuclear nitrosyl iron complexes with thiol-containing ligands (sulfur-nitrosyl iron complexes, SNIC) are considered as a promising NOdonor substance to create cardiotropic and antitumor pharmacological agents [4–6]. To date, methods of synthesis have been developed that allow creating a wide diversity of SNIC based on mercapto derivatives of aromatic nitrogen heterocycles and aliphatic sulfhydryl compounds based on amino acids [7, 8]. The release of nitric oxide by the indicated complexes occurs during a spontaneous hydrolytic dissociation in the aquatic medium [8]. At the same time, realization of such an NO-donor activity in the organism has a certain specificity related with the interaction of exogenous NO-donors with biosubstrates. As is known, the physiological activity of nitric oxide is primarily manifested in the blood, 90% of which consists of erythrocytes by its cellular composition. In relation to this, it was proposed to use the erythrocyte suspension as the model of the internal content of a blood vessel, where the pharmacological effect of nitric oxide donors in relation to the cardiovascular system is realized [9, 10].
Previous studies on the kinetics of the formation of intraerythrocyte methemoglobin in the reaction of oxyhemoglobin with nitric oxide (released upon the decomposition of SNIC) were the experime
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