Glutathione Interaction with SNS/S Mixed-Ligand Complexes of Oxorhenium(V): Kinetic Aspects and Characterization of the Products

A series of oxorhenium(V) SNS/S mixed-ligand complexes [ReO(Ln/L)] carrying different types of tridentate
ligands (Ln) and the same monodentate coligand (L) [L = C6H5S, L1 = C2H5N(CH2CH2S)2 (1), L2 = (C2H5)2NCH2CH2N(CH2CH2S)2 (2), L3 = C2H5SCH2CH2N(CH2CH2S)2 (3), and L4 = 2,6-(SCH2)2NC5H3 (4)] have been
synthesized and characterized by spectroscopic methods and elemental analyses. X-ray structure determination
was performed for complexes 3 and 4. Complex 3 adopts the expected distorted trigonal bipyramidal geometry
around the metal in a syn configuration, while complex 4, due to the aromatic character of the nitrogen of the
SNS donor-atom set, exhibits a distorted square pyramidal geometry. The interaction of complexes 1−4 with
glutathione (GSH) was studied by high-performance liquid chromatography, revealing the rapid formation of the
respective daughter complexes 5−8, wherein the L coligand has been substituted by GS. The daughter complexes
5−8 have been characterized by ES-MS and 2D NMR spectroscopy. Kinetic aspects of the interaction of complexes
1−3 with GSH have been studied by isothermal titration microcalorimetry providing direct measurements of the
interaction rate constants as well as of the total enthalpy change. The reaction of complex 1 exhibits the slowest
rate and that of complex 2 the fastest. This is in agreement with previously reported trends for analogous 99mTc
complexes.