John Baldas

Substitution reactions of 99mTcNCl4− — A route to a new class of 99mTc-radiopharmaceuticals

The preparation of sodium tetrachloronitridotechnetate Na[99mTcNCl4] is described. This complex may be used for the preparation by a substitution route of 99mTc-radiopharmaceuticals containing a Tc-nitrido(TcN) group. The labelling procedure was demonstrated by the preparation of [99mTcN]MDP, [99mTcN]DTPA and [99mTcN]cysteine. Biological distribution studies in mice of these complexes showed that the presence of the nitrido group produced a radiopharmaceutical with different biological behaviour to that produced when conventional reduction methods are used with the same ligand. HPLC studies confirmed that the use of the 99mTcNCl-4 substitution route produced radiopharmaceuticals of high radiochemical purity.

Effect of the Tc-nitrido group on the behaviour of 99mTc-radiopharmaceuticals.

The preparation of the 99mTcN-complexes of gluconate, EHDP, HIDA and PIPIDA by substitution reactions of 99mTcNCl4- is described. Studies of the distribution of these complexes in mice indicate that the presence of the Tc-nitrido group significantly alters the biological properties of the 99mTc-complexes formed using these ligands. Results suggest that the 99mTcN-complexes of these ligands are labile and undergo some ligand exchange in vivo.

Preparation of 99m Tc radiopharmaceuticals

Compounds of the formula I: R+[99m TcNX4 ]- I wherein R30 represents a cation and X represents a halo group, are prepared by reaction with an azide compound in the presence of a hydrohalic acid. The compounds are useful in production of 99m Tc-labelled radio-pharmaceuticals by reaction with ligands and monoclonal antibodies or antibody fractions.

Preparation and structure of bis(tetraphenylarsonium) trans-aquatetracyanonitridotechnetate(V) pentahydrate. ESR studies of the [TcN(CN)4(OH2)]2-/[TcNCl4]-system

Abstract The reaction of (AsPh4)[TcNCl4] with KCN and added AsPh4Cl in CH3CN/H2O yields crystals of (AsPh4)2[TcN(CN)4(OH2)]·5H2O (1). The complex crystallises in the monoclinic space group P21/n with a=17.107(5), b=19.965(7), c=15.473(5)A, β= 101.70(2)° and Z=4. Refinement with 3212 data measured with Cu Kα radiation converged at R= 0.065. The geometry of the anion is distorted octahedral with a water molecule coordinated trans to the nitrido ligand (TcOH2, 2.56(1) A). The TcN distance is 1.60(1) A. ESR studies have established the presence of two paramagnetic intermediates in the conversion of [TcN(CN)4(OH2)]2− to [TcNCl]4− in HCl solutions.

Preparation and crystal structures of [AsPh4]4[Tc4N4O2(ox)6] and [AsPh4]2[TcO(ox)2(Hox)]·3H2O: technetium complexes containing quadridentate or unidentate oxalato ligands

The reaction of oxalic acid (H2ox) with [AsPh4][TcNCl4] and [NBu4][TcOCl4] in aqueous acetone yields crystals of [AsPh4]4[Tc4N4O2(ox)6](1) and, after precipitation with AsPh4Cl, [AsPh4]2[TcO(ox)2(Hox)]·3H2O (2) respectively. Complex (1) crystallises in the monoclinic space group P21/n with cell parameters a= 14.433(1), b= 13.229(1), c= 27.020(1)A, β= 92.90(1)°, and Z= 4. Refinement with data measured with Cu-Kα radiation converged at R= 0.069 for 3 076 observed reflections. The anion in (1) is a cyclic tetranuclear complex, [Tc4N4O2(ox)6]4–, with Ci point symmetry. Each technetium(VI) atom is co-ordinated by five oxygen atoms and one nitrogen atom to give a distorted octahedron. In each half of the anion, a quadridentate oxalato ligand forms a bridge between the two octahedra, each of which is also linked to an adjacent octahedron by the corner sharing of an oxo ligand. Two oxygen atoms of a bidentate oxalato ligand and a nitrido nitrogen complete the octahedral co-ordination in each polyhedron. The Tc ⋯ Tc spacings of 3.586(2) and 5.756(3)A preclude any Tc–Tc bonding. The monoclinic crystals of complex (2) belong to the space group P21/c with a= 16.495(3), b= 14.802(2), c= 21.805(4)A, β= 98.76(1)°, and Z= 4. Refinement with 5 099 observed data measured with Mo-Kα radiation converged at R= 0.059. The technetium(V) atom is co-ordinated by six oxygen atoms to give a distorted octahedron. The structure of the anion is unusual in that it contains a protonated unidentate oxalato ligand and that there is no appreciable lengthening of the Tc–O bond trans to the oxo ligand.

Preparation of the technetium(VI) aquanitrido complexes (NEt4)[TcNX4(OH2)] (X= Cl or Br). Crystal structures of (NEt4)[TcNBr4(OH2)] and Cs2[TcNCl5]

Addition of NEt 4 X to a conc. HX solution of [TcNX 4 (OH 2 )] − (X= Cl or Br) yields crystals of (NEt 4 )[TcNX 4 (OH 2 )] (X=Cl ( 1 ) or Br ( 2 )). Complex 2 crystallises in the orthorhombic space group Pnma with a = 11.366(1), b = 12.930(2), c = 11.540(1) A and Z = 4. Refinement with 1434 data measured with Cu K α radiation converged with R = 0.047. The complex anion has distorted octahedral geometry with a water molecule trans to the nitrido ligand (TcN 1.599(9) and TcOH 2 2.443(7) A). Crystals of Cs 2 [TcNCl 5 ] ( 3 ) belong to the cubic space group Fm m with a = 10.211(1) A and Z = 4. The ligands of the complex anion are statistically disordered over six octahedral sites as required by the cubic space group. Refinement based on 78 data measured with Cu Kα radiation, and with a fixed TcN distance of 1.6 A, converged with R = 0.034. In this model Tc is displaced 0.401(3) A from the plane of the cis ligands towards the nitrido ligand with TcCl cis = 2.373(5), TcCl tras = 2.740(5) A.

The preparation, characterisation and reactions of chlorotetrakis(thiourea)nitridotechnetium(V) chloride

Preparation de [TcN(tn) 4 Cl]Cl et son utilisation pour la preparation des complexes Tc V ≡N par substitution en solution aqueuse

A spectrophotometric and ESR study of monomer, μ-oxo dimer, di(μ-oxo) dimer interconversion of nitridotechnetium(VI) complexes in solutions of sulfur and phosphorus oxo acids

Abstract UV-Vis and ESR spectroscopy have been used to study the behaviour of Cs 2 [TcNCl 5 ] and the hydrolysis product [{TcN(OH)(OH 2 )} 2 (μ-O) 2 ] ( 1 ) in concentrated and aqueous solutions of a variety of sulfur and phosphorus oxo acids ranging from the very weakly coordinating CF 3 SO 3 H to H 2 SO 4 and the coordinating acids H 3 PO 4 and H 4 P 2 O 7 . The paramagnetic monomeric Tc VI N 3− (d 1 ) forms were readily identified by ESR spectroscopy and the diamagnetic dimeric μ-oxo (Tc 2 N 2 O 4+ ) and di(μ-oxo) (Tc 2 N 2 O 2 2+ ) forms by their UV-Vis spectra. For solutions of Cs 2 [TcNCl 5 ] the chemical form of Tc VI N and the rate of the conversion of monomer→μ-oxo dimer→di(μ- oxo) dimer is dependent on the presence of Cl − and the concentration and complexing ability of the acid, with the monomeric form being favoured by the acids of greater complexing power. For solutions of 1 the reverse order of conversion was observed. In 1 M CF 3 SO 3 H, MeSO 3 H or toluene- p -sulfonic acid, 1 is converted to the di(μ-oxo) aquanitrido cation [{TcN(OH 2 ) 3 } 2 (μ-O) 2 ] 2+ while in 7.5 M CF 3 SO 3 H it is proposed that the predominant form is the μ-oxo aqua dimer [{TcN(OH 2 ) 4 } 2 (μ-O)] 4+ . In H 2 SO 4 and the phosphorus oxo acids the aqua cations are coordinated by the acid anions. The monomeric aqua cation, [TcN(OH 2 ) 5 ] 3+ , does not appear to be a viable species, as is also the case for MoO 3+ (aq), and spontaneously dimerises in 7.5 M CF 3 SO 3 H. In anhydrous CF 3 SO 3 H or H 2 SO 4 monomeric Tc VI N with CF 3 SO 3 − or HSO 4 − coordination is observed. A characteristic feature of the UV-Vis spectra of monomeric Tc VI N is a strong absorption at 266–300 nm assigned to πN→Tc charge transfer. The μ-oxo dimers show an intense visible absorption at 470–510 nm.

Structural studies of technetium complexes. Part 4. The crystal structure of trans,trans-acetonitriledi-isothiocyanato(nitrido)bis-(triphenylphosphine)technetium(V)–acetonitrile (1/0.5)

The title compound, [TcN(NCS)2(CH3CN)(PPh3)2]·0.5CH3CN, has been prepared by substitution of [TcNCl2(PPh3)2] with NH4NCS followed by the reaction of the [TcN(NCS)2(PPh3)2] complex with CH3CN. The crystal structure of [TcN(NCS)2(CH3CN)(PPh3)2]·0.5CH3CN has been determined by single-crystal X-ray diffraction methods at 25 ± 2 °C. Crystals are monoclinic, space group P21/c, with a= 9.296(3), b= 18.614(5), c= 23.307(6)A, β= 109.63(2)°, and Z= 4. Diffractometry has provided significant Bragg intensities for 5 498 independent reflections and the structure has been refined by full-matrix least-squares methods to R= 0.045. The compound consists of discrete [TcN(NCS)2(CH3CN)(PPh3)2] molecules with CH3CN of crystallisation also present in the crystal lattice. The technetium atom has a distorted octahedral environment with Tc–N–C angles of 177.1 (4) and 166.7(4)° for the NCS ligands and 168.6(4)° for the CH3CN ligand. The TcN bond distance is 1.629(4)A and the strong trans influence of the nitrido-group is evident in the exceptionally long Tc–N bond distance [2.491 (4)A] to the CH3CN ligand.

TECHNETIUM(VII) NITRIDOPEROXO COMPLEXES

Preparation of a series of technetium(VII) nitridoperoxo complexes and evidence for [TcN(O 2 )-(OH) 2 ] in solution.