Nitrosyl Iron Complex with Thiosulfate Ligands: Reaction with Glutathione

The reaction between binuclear nitrosyl iron complex (NIC) with thiosulfate ligands Na2[Fe2(S2O3)2(NO)4]•4H2O (1) and reduced glutathione (GSH) was studied. Using experimental and theoretical methods including UV spectroscopy, Griess test, and quantum chemical modeling, it was shown that the thiosulfate ligands in complex 1 are replaced by GS− to give a new binuclear nitrosyl iron complex bearing two glutathione ligands. The mechanism proposed to describe this reaction involves the addition of two glutathione molecules to complex 1 followed by consecutive detachment of thiosulfate ligands without formation of mononuclear NICs. The reaction product exhibits prolonged NO generation. The rate of NO release from the reaction product is two orders of magnitude lower than from complex 1, namely, keff = (1.8±0.1)•10−3 s−1 and keff = (2.9±0.9)•10−5 s−1 for the reaction in the absence and in the presence of GSH, respectively. The involvement of GSH in the metabolism of complex 1 treated as a promising drug can significantly influence its NO-donor properties.