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

Abstract

The coordination properties of isopropylxanthate (i-Pr-Tiox) and pyridine-2-thiolate (PyS) toward the [M(PS)2](+) moiety (M = Re and (99m)Tc; 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. (99m)Tc analogues of complexes Re2 ((99m)Tc2) and Re4 ((99m)Tc4) 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/99m)Tc 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.

Bifunctional chelators for radiorhenium: past, present and future outlook

“…52 Other co-ligands that have been studied with this core include pyridine-2-thiolate and xanthate. 126 Although only nat Re(III) complexes were evaluated in these studies, the Fig. 16 Structures of (a) SHYNIC and (b) a Re(V) oxo complex featuring two coordinated SHYNIC ligands.…”

“…ease of synthesis of the corresponding [ 99m Tc][Tc(PS) 2 (L)] complexes, as well as their excellent in vitro and in vivo stability is promising for the design of analogous radiorhenium complexes. 52,126 Additionally, the dithiocarbamate ligand may also act in a bifunctional manner by attaching to a biomolecule as well as the M(III) core, paving the way towards the potential use of radiorhenium complexes of this type in radiopharmaceutical applications. 126 Similarly, several examples of "sulphur rich" Re(III) and Tc(III) complexes have also followed this multi-ligand approach, such as the [ 188 Re]Re-(S 2 CPh)(S 3 CPh) 2 complex (or the [ 188 Re]Re-SSS complex).…”

“…52,126 Additionally, the dithiocarbamate ligand may also act in a bifunctional manner by attaching to a biomolecule as well as the M(III) core, paving the way towards the potential use of radiorhenium complexes of this type in radiopharmaceutical applications. 126 Similarly, several examples of "sulphur rich" Re(III) and Tc(III) complexes have also followed this multi-ligand approach, such as the [ 188 Re]Re-(S 2 CPh)(S 3 CPh) 2 complex (or the [ 188 Re]Re-SSS complex). 127 This radiorhenium(III) core surrounded by six coordinated sulphur atoms from three ligands (Fig.…”

“…Fig 19. Structures of (a) complexes of the type [M(PS) 2 (L)] (M = 99m Tc(III) and Re(III))126 and (b) the [188 Re]Re(III)-SSS complex 91. …”

New Insights in the Design of Bioactive Peptides and Chelating Agents for Imaging and Therapy in Oncology

“…Labeling of peptides with 99m Tc is usually based on ligands containing N 2 S 2 diamidedithiols, N 3 S triamidethiols, N4 tetraamines [ 80 , 81 ], hydrazine nicotinic acid (HYNIC) [ 82 , 83 , 84 ] or phosphines [ 85 , 86 , 87 , 88 ] ( Figure 2 ). Labeling reactions require high temperatures (80–100 °C), except for N 4 which reacts at room temperature.…”