Novel Oxorhenium and Oxotechnetium Complexes from an Aminothiol[NS]/Thiol[S] Mixed-Ligand System

Abstract

The simultaneous action of a bidentate aminothiol ligand, LnH, (n = 1: (CH3CH2)2NCH2CH2SH and n = 2: C5H10NCH2CH2SH) and a monodentate thiol ligand, LH (LH: p-methoxythiophenol) on a suitable MO (M = Re, 99gTc) precursor results in the formation of complexes of the general formula [MO(Ln)(L)3] (1, 2 for Re and 5. 6 for 99gTc). In solution these complexes gradually transform to [MO(Ln)(L)2] complexes (3, 4 for Re and 7, 8 for 99gTc). The transformation is much faster for oxotechnetium than for oxorhenium complexes. Complexes 1-4, 7, and 8 have been isolated and fully characterized by elemental analysis and spectroscopic methods. Detailed NMR assignments were made for complexes 3, 4, 7, and 8. X-ray studies have demonstrated that the coordination geometry around rhenium in complex 1 is square pyramidal (tau = 0.06), with four sulfur atoms (one from the L1H ligand and three from three molecules of p-methoxythiophenol) in the basal plane and the oxo group in the apical position. The L1H ligand acts as a monodentate ligand with the nitrogen atom being protonated and hydrogen bonded to the oxo group. The four thiols are deprotonated during complexation resulting in a complex with an overall charge of zero. The coordination geometry around rhenium in complex 4 is trigonally distorted square pyramidal (tau = 0.41), while in the oxotechnetium complex 7 it is square pyramidal (tau = 0.16). In both complexes LnH acts as a bidentate ligand. The NS donor atom set of the bidentate ligand and the two sulfur atoms of the two monodentate thiols define the basal plane, while the oxygen atom occupies the apical position. At the technetium tracer level (99mTc), both types of complexes, [99mTcO(Ln)(L)3] and [99mTcO(Ln)(L)2], are formed as indicated by HPLC. At high ligand concentrations the major complex is [99mTcO(Ln)(L)3], while at low concentrations the predominant complex is [99mTcO(Ln)(L)2]. The complexes [99mTcO(Ln)(L)3] transform to the stable complexes [99mTcO(Ln)(L)2]. This transformation is much faster in the absence of ligands. The complexes [99mTcO(Ln)(L)2] are stable, neutral, and also the predominant product of the reaction when low concentrations of ligands are used, a fact that is very important from the radiopharmaceutical point of view.

Synthesis and Characterization of Novel Oxotechnetium (99Tc and 99mTc) and Oxorhenium Complexes from the 2,2‘-Bipyridine (NN)/Thiol (S) Mixed-Ligand System

“…Our laboratory has been involved in the design and synthesis of potential radiopharmaceuticals utilizing the TcO(V) 3+ and ReO(V) 3+ cores that give stable, pentacoordinated or hexacoordinated complexes with a variety of ligands carrying the S and N donor atoms. In these studies, the “3 + 1”, “2 + 1 + 1”, “3 + 1 + 1”, or “3 + 2” ligand combinations have been applied in the preparation of a variety of neutral complexes of the MO[SNS][S], 6a,b,d MO[SNN][S], 6c,e MO[SN][S][S], 6e,f and MO[SNN][S][S] 6g types, respectively, where M = Tc and/or Re. The mixed-ligand approach allows the tuning of the physicochemical properties and biodistribution of the complexes synthesized.…”

Spectroscopic investigation and density functional theory calculations of mercaptobenzothiazole and mercaptobenzimidazole ligands and their rhenium complexes

“…ReO(citrate) 2 -and ReO(gluconate) 2 -precursors were prepared according to literature [5,6] respectively. IR spectroscopy was recorded on a Perkin Elmer spectro-photometer 1000 in the spectral range 200 -4000 cm -1 with sample in the form of KBr pellets.…”

“…C NMR spectra were measured in (DMSO-d 6 and CDCl 3 ) as solvents on a JOEL-NMR 400 MHz spectrometer. Micro-analytical (CHN) were run at the Mikronalytisches Labor Pascher, Germany.…”

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

“…Amino (1 mmol, 0.1004 g) and mer (2 mmol, 0.334 g) in ethanol were added dropwise to the mixture. The reaction mixture was stirred at room temperature for 3 h. The pH was adjusted to 9 with NaOH (0.5 M), and the precipitate was recrystallized in hot methanol and acetone according to [17]. We failed to prepare a single crystal, and the complex was precipitated in microcrystalline form in 98% yield.…”