Synthesis and characterization of a {ReO}3+ complex with S- and N-donor ligands and of its 99m Tc analog

Abstract

A novel mixed-ligand 99m Tc complex with mercaptobenzothiazole (mer) as ligand and aminothiazole (amino) as coligand was prepared and evaluated as potential brain radiopharmaceutical. Preparation at tracer level was accomplished by substitution, using 99m Tc-gluconate as precursor and a coligand/ligand ratio of 5. Under these conditions, the labeling yield was over 97% and the major product with radiochemical purity >97% was isolated by HPLC and used for biological evaluation. The reaction of [ReO(Citrate) 2 ] -with mer and amino in hot MeOH yields [ReO(mer)(amino)OH(H 2 O) 2 ]. The DFT study demonstrated that the complex contains distorted octahedral ReO(V). The Re coordination sphere consists of the terminal oxo group, the S donor atom of the deprotonated mer, the N atom of the deprotonated amino, OH group, and two water molecules. Biodistribution in mice demonstrated early brain uptake, fast blood clearance, and excretion through hepatobiliary system. Although the brain/blood ratio increased significantly with time, the novel 99m Tc complex did not exhibit ideal properties as brain perfusion radiopharmaceutical since brain uptake was too low.The γ-emitting 99m Tc is the most widely applied radionuclide in diagnostic imaging. Nevertheless, current research in radiopharmacology deals with the coordination chemistry of Tc as well as its congener Re with the aim to develop new radiotracers [1,2]. In the past decade, many efforts were focused on brainimaging Tc radiopharmaceuticals capable to cross the blood-brain barrier and localize in the brain. Although many of the Tc and Re complexes have been investigated to date, clear structural criteria involved in brain uptake and retention of technetium complexes are not fully documented.One of the important aspects in Tc radiotracer design is the complex lipophilicity [3]. Since distribution and passive transport through membranes are governed by lipophilicity, there is considerable interest in how lipophilicity parameters can be controlled by chemical modifications of the tracer molecule. This study on amine-bearing mixed-ligand Re complexes aims toward this goal. These studies are triggered by the fact that the amine-carrying Tc species are able to pass the intact blood-brain barrier and are accumulated in the brain [4,5]. Keeping in mind that Re complexes may serve as nonradioactive surrogates for their Tc analogs due to similar molecular properties, we studied Re(V) whose coordination core is stable enough to exist in aqueous solutions and versatile enough to combine with selected ligands. An example of such a core is the oxo form [Re V O] 3+ , in which the +5 oxidation state of the metal is stabilized by the oxo ligand [5,6]. The literature shows that a search for new radiopharmaceuticals requires studies of new oxorhenium(V) complexes with N-and S-donor ligands, as well as of their 99m Tc analogs. In this study we prepared and characterized a novel rhenium complex, [ReO(mer)(amino)OH· (H 2 O) 2 ]. We have also studied the radiochemical properties of the correspond...

Synthesis and Photochemical Properties of Re(I) Tricarbonyl Complexes Bound to Thione and Thiazol-2-ylidene Ligands

“…We therefore sought to investigate Re­(I) tricarbonyl NHC complexes where the NHC ligand was characterized by a N^C^S motif, as a comparative study to our previous Re­(I) NHC complexes. Furthermore, we endeavored to prepare the analogous complexes by binding the precursor ligand containing the thiazolethione functional group to the Re­(I) center, given that Re­(I) complexes coordinated to thione ligands are not currently common in the literature. − The work presented herein describes the synthesis and structural determination of these complexes, along with the investigation of their ligand substitution reactions from the ground and excited states through a combination of UV–vis, IR, and NMR spectroscopy.…”

Synthesis and Photochemical Properties of Re(I) Tricarbonyl Complexes Bound to Thione and Thiazole-2-ylidene Ligands

“…Furthermore, we endeavoured to prepare the analogous complexes by binding the precursor ligand containing the thiazolethione functional group to the Re(I) centre, given Re(I) complexes coordinated to thiazole-2-thione ligands are not currently common in the literature. [42][43][44][45][46][47] The work presented herein describes the synthesis and structural determination of these complexes, along with the investigation of their ligand substitution reactions from the ground and excited states through a combination of UV-Vis, IR and NMR spectroscopies.…”