Rhenium(v) oxocomplexes with novel pyrazolyl-based N4- and N3S-donor chelators

Abstract

The novel pyrazolyl-based ligands 3,5-Me₂pz(CH₂)₂NH(CH₂)₂NH(CH₂)₂NH₂ (1) and pz*(CH₂)₂NH-Gly-CH₂STrit (pz* = pz (8), 3,5-Me₂pz (9), 4-(EtOOC)CH₂-3,5-Me₂pz (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-Me₂pz(CH₂)₂N(CH₂)₂NH(CH₂)₂NH₂}](BPh₄) (11) in a low isolated yield. In contrast, the neutral complexes [ReO{pz*(CH₂)₂NH-Gly-CH₂S}] (pz* = pz (12), 3,5-Me₂pz (13), 4-(EtOOCCH₂)-3,5-Me₂pz (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 (¹H COSY and ¹H/¹³C 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 [^99mTcO{pz(CH₂)₂-NH-Gly-CH₂S}] (12a). This radioactive compound was obtained from ^99mTcO₄⁻ in aqueous medium, in almost quantitative yield and with high specific activity and radiochemical purity.