Thiol- and Thioether-Based Bifunctional Chelates for the {M(CO)₃}⁺ Core (M = Tc, Re)

Abstract

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)2NCH2CH2SEt (L1); (NC5H4CH2)2NCH2CH2SH (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)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 approximately thiolate > carboxylate > thioether sulfur > thiophene sulfur. The ligands L1 and L2 react cleanly with [99mTc(CO)3(H2O)3]+ in H2O/DMSO to give [99mTc(CO)3(L1)]+ (99m)Tc-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.

Functionalised Tris(pyrazolyl)methane Ligands and Re(CO)3 Complexes Thereof

“…[44] The microwave assisted reaction in water / ethanol proceeds smoothly but yields the pyrazole complex as product of hydrolysis. It was identified by IR spectroscopy and mass spectrometry as [(Hpz) 2 Re(CO) 3 Br] (7a).…”

“…The tris(3-R-pyrazolyl)methanes (R = H, Ph, tert.-Bu) [29] , 3,3,3-tris(pyrazolyl)propane [50] and [Re(H 2 O) 3 (CO) 3 ]Br [44] were prepared according to published procedures. The preparation of the ligands was carried out in Schlenk tubes under an atmosphere of dry nitrogen using anhydrous solvents purified according to standard procedures.…”

“…[30][31][32] This is interesting for therapeutic as well as diagnostic purposes as rhenium has two isotopes with favourable β-emitting properties ( 188 Re, t ½ = 16.9 h, E β = 2.1 MeV; 186 Re, t ½ = 3.78 d, E β = 1.07 MeV, E γ = 137 keV) and additionally, the Re(CO) 3 core resembles the diagnostically important 99m Tc(CO) 3 core. [18,[33][34][35][36][37][38] For the attachment of the ligands to e.g. a polymeric backbone, an additional functional group has to be present in the molecule.…”

Synthesis, Cytotoxicity, and Insight into the Mode of Action of Re(CO)3 Thymidine Complexes

“…Upon metal coordination, the protons of the pyridine rings as well as protons in a-position to the tertiary nitrogen atom of the chelate exhibited a strong downfield shift in the NMR spectra, which is consistent with reports on similar organorhenium complexes (see Figure 2). [23][24][25]30] The de-shielding is most pronounced for the aliphatic methylene protons of the dipicolyl moiety, shifting from~3.8 to 5.0 ppm after metal coordination. In addition, the observed AB coupling pattern of these methylene protons is indicative for a facial coordination of the rhenium tricarbonyl core to the tridentate chelate.…”

“…[19][20][21][22][23] The corresponding technetium and rhenium precursors [M(CO) 3 (H 2 O) 3 ] + 1 can be conveniently accessed by synthetic procedures, are water soluble, and the three aqua ligands are labile and can readily undergo ligand exchange. [24][25][26] The [M(CO) 3 ] + 1 core is chemically robust, and complexes are chemically inert because of the d 6 low-spin electronic configuration, thus maintaining their integrity under the most forcing conditions. Whereas 99m…”