Nitric oxide donation by the binuclear tetranitrosyl iron complexes in the presence of erythrocytes

Abstract

The kinetic regularities of nitric oxide donation in the presence of erythrocytes by representatives of a new class of synthetic nitric oxide donors, binuclear tetranitrosyl iron complexes (B-TNIC) [Fe2(SR)2(NO)4] with thiol-containing ligands, where R is pyrimidin-2-yl, 1-methylimidazol-2-yl, benzothiazol-2-yl, and penicillamine residue, were established. The NO-donating ability of B-TNIC was estimated from the apparent rate constants of the first order for the formation of intraerythrocyte methemoglobin with the variation of the initial concentration of the complex. During the standard experimental time (15—17 min), three of the four complexes released in the solution no more than a quarter of available NO groups. Their NO-donating ability turned out to be variable increasing with an increase in the initial concentration of the complex. At the same time, the complex bearing penicillamine residues as ligands donated almost all NO groups within approximately 1 min. Features of NO donation by the B-TNIC in the presence of erythrocytes are related to the formation in the system of an additional equilibrium pool of the membrane-associated complex, which is characterized by a reduced rate of hydrolytic dissociation with NO releasing to the solution. The NO-donating ability of the B-TNIC in the presence of erythrocytes is determined by the ratio of volumes of the free and membrane-associated pools of the complex.