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 ligand [L¹: C₂H₅N(CH₂CH₂S)₂, L²: (C₂H₅)₂NCH₂CH₂N(CH₂CH₂S)₂, L³: C₂H₅SCH₂CH₂N(CH₂CH₂S)₂ and L⁴: 2,6-(SCH₂)₂NC₅H₃] and the same monodentate coligand (L: C₆H₅S) 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 (HPLC), 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 a battery of NMR measurements involving HETCOR, COSY and NOESY procedures. Kinetic aspects of the interaction of complexes 1 ¾ 3 with GSH have been studied by isothermal titration microcalorimetry providing direct measurements of the interaction rate constants as well as the total enthalpy change. The reaction of complex 1 is characterized by the slowest and that of complex 2 by the fastest rate. This is in agreement with previously reported trends for analogous ^99mTc complexes.