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)₂NCH₂CH ₂SEt (L1); (NC₅H₄CH₂) ₂NCH₂CH₂SH (L2); NC₅H ₄CH₂N(CH₂CH₂SH)₂ (L3); (NC₅H₄CH₂)N(CH₂CH ₂SH)(CH₂CO₂R) [R = H (L4); R = -C ₂H₅ (L5). The {Re(CO)₃}⁺ core complexes of L1-L5 were prepared by the reaction of [Re(CO)₃(H ₂O)₃]Br or [NEt₄]₂[Re(CO) ₃Br₃] with the appropriate ligand in methanol and characterized by infrared spectroscopy, ¹H and ¹³C NMR spectroscopy, mass spectrometry, and in the case of [Re(CO)₃(L2)] (Re-2) and [Re(CO)₃(L1)Re(CO)₃Br₂] (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-1a consists of discrete binuclear units, constructed from a {Re(CO)₃(L1)} ⁺ subunit linked to a {Re(CO)₃Br₂}^- 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 [^99mTc(CO)₃(H ₂O)₃]⁺ in H₂O/DMSO to give [ ^99mTc(CO)₃(L1)]⁺ (^99mTc-1) and [^99mTc(CO)₃(L2)] (^99mTc-2), respectively, in ca. 90% yield after HPLC purification. The Tc analogues ^99mTc-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.