Reversible Dissociation and Ligand-Glutathione Exchange Reaction in Binuclear Cationic Tetranitrosyl Iron Complex with Penicillamine

摘要

This paper describes a comparative study of the decomposition of two nitrosyl iron complexes (NICs) with penicillamine thiolic ligands [Fe2(SC5H11NO2)2(NO)4]SO4 ·5H2O (>I) and glutathione- (GSH-) ligands [Fe2(SC10H17N3O6)2(NO)4]SO4 ·2H₂O (>II), which spontaneously evolve to NO in aqueous medium. NO formation was measured by a sensor electrode and by spectrophotometric methods by measuring the formation of a hemoglobin- (Hb-) NO complex. The NO evolution reaction rate from (>I)  k ₁ = (4.6 ± 0.1)·10⁻³ s⁻¹ and the elimination rate constant of the penicillamine ligand k ₂ = (1.8 ± 0.2)·10⁻³ s⁻¹ at 25°C in 0.05 M phosphate buffer,  pH 7.0, was calculated using kinetic modeling based on the experimental data. Both reactions are reversible. Spectrophotometry and mass-spectrometry methods have firmly shown that the penicillamine ligand is exchanged for GS⁻ during decomposition of 1.5·10⁻⁴ M (>I) in the presence of 10⁻³ M GSH, with 76% yield in 24 h. As has been established, such behaviour is caused by the resistance of (>II) to decomposition due to the higher affinity of iron to GSH in the complex. The discovered reaction may impede S-glutathionylation of the essential enzyme systems in the presence of (>I) and is important for metabolism of NIC, connected with its antitumor activity.