Influence of ligand lipophilicity on the NO-donating ability of the binuclear tetranitrosyl iron complexes in an erythrocyte suspension

Abstract

The kinetics of nitric oxide release by representatives of a new class of synthetic nitric oxide donors, binuclear tetranitrosyl iron complexes (B-TNIC) with a structure of [Fe2(SR)2(NO)4], where R is pyrimidin-2-yl, 1-methylimidazol-2-yl, benzothiazol-2-yl, cysteamine, and penicillamine, was studied under the conditions simulating the blood vessel internal environment, when an erythrocyte suspension was used as a natural trap of nitric oxide. The apparent firstorder rate constants for intraerythrocyte methemoglobin formation were determined on the basis of the kinetic data. The NO-donating ability of B-TNIC was estimated from the values of these rate constants. It is assumed that the rate for the hydrolytic decomposition of B-TNIC decreases in the presence of erythrocytes due to binding of the complexes with the cell surface, leading to the restriction of their contact with an aqueous medium. Nitric oxide donating by the complex bearing penicillamine as a ligand is stoichiometric and independent of the presence of erythrocytes. This can be due to high hydrophilicity of this complex determined from the criterion of partition coefficient in an octanol-water system. This evidently provides a high level of solvation of the complex in an aqueous medium that prevents its binding with the erythrocyte surface.