Reactivity of the [M(PS)₂]⁺ Building Block (M = Re^III and ^99mTc^III; PS = Phosphinothiolate) toward Isopropylxanthate and Pyridine-2-thiolate

The coordination properties of isopropylxanthate (i-Pr-Tiox) and pyridine-2-thiolate (PyS) toward the [M­(PS)₂]⁺ moiety (M = Re and ^99mTc; PS = phosphinothiolate) were investigated. Synthesis and full characterization of [Re­(PS2)₂(i-Pr-Tiox)] (Re1), [Re­(PSiso)₂(i-Pr-Tiox)] (Re2), [Re­(PS2)₂(PyS)] (Re3), and [Re­(PSiso)₂(PyS)] (Re4), where PS2 = 2-(di­phenyl­phosphino)­ethane­thiolate and PSiso = 2-(di­isopropyl­phosphino)­ethane­thiolate, and the structural X-ray analysis of complex Re3 were carried out. ^99mTc analogues of complexes Re2 (^99mTc2) and Re4 (^99mTc4) were obtained in high radiochemical yield following a simple one-pot procedure. The chemical identity of the radiolabeled compounds was confirmed by chromatographic comparison with the corresponding rhenium complexes and by dual radio/UV HPLC analysis combined with ESI­(+)-MS of ^99g/99mTc complexes prepared in carrier-added conditions. The two radiolabeled complexes were stable with regard to trans chelation with cysteine, glutathione, and ethylene­diamino­tetra­acetic acid and in rat and human sera. This study highlights the substitution-inert metal-fragment behavior of the [M­(PS)₂]⁺ framework, which reacts with suitable bidentate coligands to form stable hexacoordinated asymmetrical complexes. This feature makes it a promising platform on which to develop a new class of Re/Tc complexes that are potentially useful in radiopharmaceutical applications.