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The present paper deals with the synthesis and structural characterization of novel neutral oxorhenium(V) complexes of the general formula ReO[SNO][NN]. The simultaneous action of the tridentate SNO ligand, N-(2-mercaptoacetyl)glycine (1), and the bidentate NN ligand, N-phenylpyridine-2-aldimine (2), on ReOCl3(PPh3)2 leads to the formation of two isomers 4a and 4b of the general formula ReO[SNO][NN], as a result of the different orientations of the NN ligand. In both cases, the SNO donor atoms of the tridentate ligand occupy the three positions in the equatorial plane of the distorted octahedron, whereas the oxo group is always directed toward one of the apical positions. In the first isomer, 4a, the imino nitrogen of the NN ligand occupies the fourth equatorial position and the pyridine type nitrogen is directed trans to the oxo group, while in the second isomer, 4b, the imino nitrogen of the NN ligand occupies the apical position trans to the oxo group and the pyridine type nitrogen completes the equatorial plane of the distorted octahedron. The [SNO][NN] mixed-ligand system was applied in the synthesis of the oxorhenium complex 5 in which the 1-(2-methoxyphenyl)piperazine moiety, a fragment of the true 5-HT1A antagonist WAY 100635, has been incorporated in the NN bidentate ligand (NN is N-{3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl}pyridine-2-aldimine). In this case, high-performance liquid chromatography and NMR showed the existence of one isomer, 5, in which the pyridine nitrogen is trans to the oxo core, as demonstrated by crystal structure analysis.

Rhenium and technetium are known for their useful applications in nuclear medicine with similar properties. In this study, new diamido dipyridino (N(4)) water-soluble ligands (2-C(5)H(4)NCH(2)NHCO)(2)CH(2), 1 (L(1)H2), (2-C(5)H(4)NNHNHCO)(2)CH(2), 2, and [2-C(5)H(4)N(+)(O)(-)CH(2)NHCO](2)CH(2), 3, were synthesized. Reaction of L(1)H2 with ReOCl(3)(PPh(3))(2) resulted in the novel six-coordinated rhenium(V) complex, trans-ReO(L(1))(OEt), 4. The complex was characterized by spectroscopic methods, and its X-ray crystallographic analysis revealed that rhenium is coordinated to four nitrogen atoms of the ligand and to two oxygen atoms from the deprotonated ethanol and the oxo group respectively in a distorted octahedral geometry. In solution, complex 4 was transformed to a new complex 5, which was proved to be the dinuclear complex mu-oxo [ReO(L(1))](2)O. Reaction of 1 with [n-Bu(4)N][ReOCl(4)] resulted in the neutral complex 6, trans-[ReO(L(1))]Cl. Similarly, when ligand 1 was reacted with [n-Bu(4)N][(99g)TcOCl(4)], the neutral trans-[(99)TcO(L(1))]Cl complex 7 was formed, which upon dissolution transformed into a cationic complex 8, trans-[(99)TcO(L(1))(OH(2))](+)Cl(-). The single-crystal X-ray structure of 8 reveals that the coordination sphere about technetium is a distorted octahedron with four nitrogen atoms in the equitorial plane, while doubly bonded oxygen and coordinated water occupy the apical positions. Further dissolution of 8 resulted in the formation of dinuclear mu-oxo [TcO(L(1))](2)O, 9. This study shows that Tc and Re have similar metal core structures in solution for diamido dipyridino systems, besides similarity in geometrical structure, proved by the X-ray structures on the same ligands.

The [NS][S](2) mixed-ligand system was applied to synthesize oxorhenium and oxotechnetium complexes of the general formula MO(o-CH(3)OC(6)H(4)N(CH(2)CH(2))(2)NCH(2)CH(2)S)(p-CH(3)C(6)H(4)S)(2) (M=Re in 1, M=(99)Tc in 2, and M=(99m)Tc in 3). The bidentate [NS] ligand includes the 1-(2-methoxyphenyl)piperazine moiety which is a fragment of the true 5-HT(1A) antagonist WAY 100635. The oxorhenium complex 1 was prepared by a ligand exchange reaction using ReOCl(3)(PPh(3))(2) as precursor while [Bu(4)N][(99)TcOCl(4)] and (99)Tc-gluconate were used as precursors in the synthesis of the oxotechnetium-99 complex 2. Both complexes were characterized by elemental analysis and spectroscopic methods. Crystallographic analysis of 1 showed that the rhenium coordination geometry is trigonal bipyramidal. The basal plane of the trigonal bipyramid is defined by the oxo group and two sulphur atoms, one belonging to the [NS] ligand and the other to an aromatic thiol, while the apical positions are occupied by the nitrogen of the [NS] ligand and the sulphur of the second aromatic thiol. The oxotechnetium-99 complex 2 has almost identical unit cell parameters to those of the oxorhenium complex 1 indicating, in combination with the other analytical data, that the complexes are isostructural. The binding affinity of the oxorhenium complex 1 for the 5-HT(1A) receptor subtype was determined in rat brain hippocampal preparations (IC(50)=106 nM). The oxotechnetium-99m complex 3 was prepared by a ligand exchange reaction using (99m)Tc-glucoheptonate as the precursor. Its structure was established by comparative HPLC studies using the oxotechnetium-99 complex 2 as a reference. Complex 3 was administered by intravenous injection in rats. At 2 min post injection, 0.153% of the injected dose per gram of tissue was measured in rat brain.

The synthesis, characterization and biological evaluation of two novel 3 + 1 mixed ligand 99mTc-complexes, bearing the 1-(2-methoxyphenylpiperazine) moiety, a fragment of the true 5-HT1A antagonist WAY 100635, is reported. Complexes at tracer level 99mTcO[(CH3CH2)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N(CH2CH2)2NCH2CH2S], 99mTc-1, and 99mTcO[((CH3)2CH)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N (CH2CH2)2NCH2CH2S], 99mTc-2, were prepared using 99mTc-glucoheptonate as precursor. For structural characterization, the analogous oxorhenium complexes, Re-1 and Re-2, were prepared by ligand exchange reaction using ReOCl3(PPh3)2 as precursor, and characterized by elemental analysis and spectroscopic methods. Complex Re-1 was further characterized by crystallographic analysis. Labeling was performed with high yield (>85%) and radiochemical purity (>90%) using very low ligand concentration. The structure of 99mTc complexes was established by comparative HPLC using the well-characterized oxorhenium analogues as references. In vitro binding assays demonstrated the affinity of these complexes for 5-HT1A receptors (IC50 : 67 and 45 nM for Re-1 and Re-2 respectively). Biological studies in mice showed the ability of 99mTc-1 and 99mTc-2 complexes to cross the intact blood-brain barrier (1.4 and 0.9% dose/g, respectively at 1 min post-inj.). The distribution of these complexes in various regions in rat brain is inhomogeneous. The highest ratio between areas reach and poor in 5-HT1A receptors was calculated for complex Tc-1 at 60 min p.i. (hippocampus/cerebellum = 1.7).

Novel oxorhenium and oxotechnetium complexes based on the tetradentate 1-(2-hydroxybenzamido)-2-(pyridinecarboxamido)benzene, H3L, ligand have been synthesized and characterized herein. Thus, by reacting equimolar quantities of the triply deprotonated ligand L3- with the suitable MO3+ precursor, the following neutral MOL complexes could be easily produced following similar synthetic routes: M = Re (1), M = 99gTc (2), and M = 99mTc (3). Complexes 1 and 2, prepared in macroscopic amounts, were chemically characterized and their structure determined by single-crystal X-ray analysis. They are isostructural metal chelates, adopting a distorted square pyramidal geometry around the metal. The N3O donor atom set of the tetradentate ligand defines the basal plane and the oxygen atom of the M = O core occupies the apex of the pyramid. Complex 3 forms quantitatively at tracer level by mixing the H3L ligand with Na99mTcO4 generator eluate in aqueous alkaline media and using tin chloride as reductant in the presence of citrate. Its structure was established by chromatographic comparison with prototypic complexes 1 and 2 using high-performance liquid chromatographic techniques. When challenged with excess glutathione in vitro, complex 3 is rapidly converted to hydrophilic unidentified metal species. Tissue distribution data after administration of complex 3 in vivo revealed a significant uptake and retention of this compound in brain tissue.