Rhenium(V) oxocomplexes with novel pyrazolyl-based N-4- and N3S-donor chelators

摘要

The novel pyrazolyl-based ligands 3,5-Me(2)pz(CH2)(2)NH(CH2)(2)NH(CH2)(2)NH2 (1) and pz*(CH2)(2)NH-Gly-CH(2)STrit (pz* = pz (8), 3,5-Me(2)pz (9), 4-(EtOOC)CH2-3,5-Me(2)pz (10)) were synthesized, and their suitability to stabilize Re(v) oxocomplexes was evaluated using different starting materials, namely (NBu4)[ReOCl4], [ReOCl3(PPh3)(2)] and trans-[ReO2(py)(4)]Cl. Compound 1 reacts with trans-[ReO2(py)(4)]Cl yielding the cationic compound [ReO(OMe){3,5-Me(2)pz(CH2)(2)N(CH2)(2)NH(CH2)(2)NH2}](BPh4) (11) in a low isolated yield. In contrast, the neutral complexes [ReO{pz*(CH2)(2)NH-Gly-CH2S}] (pz* = pz (12), 3,5-Me(2)pz (13), 4-(EtOOCCH2)-3,5-Me(2)pz (14)) were synthesized almost quantitatively by reacting [ReOCl3(PPh3)(2)] or (NBu4)[ReOCl4] with the trityl-protected chelators 8-10. The X-ray diffraction analysis of 11 and 13 confirmed the tetradentate coordination mode of the respective ancillary ligands. In 11 the monoanionic chelator coordinates to the metal through four nitrogen atoms, while in 13 the chelator is trianionic, coordinating to the metal through three nitrogens and one sulfur atom. Solution NMR studies of 12-14, including two-dimensional NMR techniques (H-1 COSY and H-1/C-13 HSQC), confirmed that the N3S coordination mode of the chelators is retained in solution. Unlike 11, complexes 12-14 may be considered relevant in the development of radiopharmaceuticals, as further corroborated by the synthesis of the congener [(TcO)-Tc-99m{pz(CH2)(2)-NH-Gly-CH2S}] (12a). This radioactive compound was obtained from (TcO4-)-Tc-99m in aqueous medium, in almost quantitative yield and with high specific activity and radiochemical purity.