Thiol- and thioether-based bifunctional chelates for the {M(CO)3]+ core (M = Tc, Re)

By analogy to the recently described single amino acid chelate (SAAC) technology for complexation of the {M(CO)(3)}(+) core (M = Tc, Re), a series of tridentate ligands containing thiolate and thioether groups, as well as amino and pyridyl nitrogen donors, have been prepared: (NC5H4CH2)(2)NCH2CH2SEt (L1); (NC5H4CH2)(2)NCH2CH2SH (L2); NC5H4CH2N(CH2CH2SH)2 (L3); (NC5H4CH2)N(CH2CH2SH)(CH2CO2R) [R = H (L4); R = -C2H5 (L5). The {Re(CO)(3)}(+) core complexes of L1-L5 were prepared by the reaction of [Re(CO)(3)(H2O)(3)]Br or [NEt4](2)[Re(CO)(3)Br-3] with the appropriate ligand in methanol and characterized by infrared spectroscopy, H-1 and C-13 NMR spectroscopy, mass spectrometry, and in the case of [Re(CO)(3)(L2)] (Re-2) and [Re(CO)(3)(L1)Re(C0)(3)Br-2] (Re-1a) by X-ray crystallography. The structure of Re-2 consists of discrete neutral monomers with a fac-Re(CO)3 coordination unit and the remaining coordination sites occupied by the amine, pyridyl, and thiolate donors of L2, leaving a pendant pyridyl arm. In contrast, the structure of Re-la consists of discrete binuclear units, constructed from a {Re(CO)(3)-(L1)}(+) subunit linked to a {Re(CO)(3)Br-2}(-) group through the sulfur donor of the pendant thioether arm. The series of complexes establishes that thiolate donors are effective ligands for the {M(CO)(3)}(+) core and that a qualitative ordering of the coordination preferences of the core may be proposed: pyridyl nitrogen - thiolate > carboxylate > thioether sulfur > thiophene sulfur. The ligands L1 and L2 react cleanly with [Tc-99m(CO)(3)(H2O)(3)](+) in H2O/DMSO to give [99mTc(CO)(3)(L1)]+ (Tc-99m-1) and [Tc-99m(CO)(3)(L2)] (Tc-99m-2), respectively, in ca. 90% yield after HPLC purification. The Tc analogues Tc-99m-1 and 99mTc-2 were subjected to ligand challenges by incubating each in the presence of 1000-fold excesses of both cysteine and histidine. The radiochromatograms showed greater than 95% recovery of the complexes.