Reactions of the [Fe(CN)5NO]2− complex with biologically relevant thiols

Abstract

Reactions of the [Fe(CN)₅NO]²⁻ complex with biologically relevant thiols (H_nRS = cysteine, N-acetylcysteine, ethyl cysteinate and glutathione) are initiated by the nucleophilic attack of a thiolate (RSⁿ⁻) on the N atom of the NO⁺ ligand in the complex to form [Fe(CN)₅N(O)SR]⁽ⁿ⁺²⁾⁻. The N–S bond in the latter complex is, however, weak and can undergo both heterolytic and homolytic splitting. The former process makes the synthesis reaction reversible, whereas the latter is responsible for the spontaneous redox decomposition: [Fe(CN)₅N(O)SR]⁽ⁿ⁺²⁾⁻ → [Fe^I(CN)₅NO]³⁻ + RS˙⁽ⁿ⁻¹⁾⁻. The rate of the monomolecular reaction is controlled by an inductive effect in the thiol with an additional stabilisation coming from formation of a six-membered ring in the case of the N-acylated compounds. In the presence of thiolate excess, the RS˙⁽ⁿ⁻¹⁾⁻ radicals are transformed into the more stable RSSR˙^(2n−1)− radicals, which are scavenged by both [Fe(CN)₅N(O)SR]⁽ⁿ⁺²⁾⁻ and [Fe(CN)₅NO]²⁻. The former reaction initiates, whereas the latter terminates, chain reactions of the catalysed redox decomposition. The catalytic decomposition (in the thiol excess) is much faster than the spontaneous decay (in the nitroprusside excess) but leads to the same final products. The Fe(I) reduction product is identified by UV/Vis, IR, electrochemical and EPR methods. The effect of molecular oxygen is investigated and explained. The mechanism is interpreted in terms of intermediate [Fe(CN)₅N(O)(SR)₂]^(2n+2)− complex formation via nucleophilic attack and its decay mainly via homolytic splitting of the N–S bond. To verify the mechanism, a simple reaction model is constructed, based on the assumption that the RSNO⁽ⁿ⁻¹⁾⁻ ligands are mostly responsible for the [Fe(CN)₅N(O)(SR)]⁽ⁿ⁺²⁾⁻ reactivity and their electronic properties are discussed within the DFT framework.