The Chemistry of Technetium–Water Complexes within the Manganese Triad: Challenges and Perspectives

Abstract

The chemistry of technetium is essentially driven by radiopharmaceutical applications. These comprise the syntheses of novel complexes but, moreover, the combination of targeting biomolecules with metal complexes. Aqua ions are especially convenient for facilitatating the introduction of metal cations into biomolecules, but are nonexistent for Tc and Re in the Mn triad. This microreview will discuss the chemistry of those Tc complexes that contain H2O as ligands. Special attention will be payed to organometallic aqua ions, i.e. complexes that are typically organometallic with water as ligand. Of particular interest is the coordination chemistry of [M(OH2)3(CO)3]+ (M = Mn, Tc, Re) complexes in water since it is the origin of the widely applied radiopharmaceutical research with 99mTc and 188Re. The chemistry of organometallic aqua ions is not confined to Werner‐type ligands, hence, a further emphasis will be placed on pure organometallic chemistry in water.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Remarkable Brain Penetration of Cyclopentadienyl M(CO)3+ (M = 99mTc, Re) Derivatives of Benzothiazole and Benzimidazole Paves the Way for Their Application as Diagnostic, with Single-Photon-Emission Computed Tomography (SPECT), and Therapeutic Agents for Alzheimer’s Disease

“…In this work, the new agents preserve main structural features of 2-arylbenzothiazole, such as planarity, length, neutrality, and chemical properties, like fluorescence and affinity for Aβ plaques, whereas the compactness of the structure and added lipophilicity provided by the [CpMCO 3 ] (M = Re, 99m Tc) core obviously contributes to their impressive brain uptake. The results support the notion that piano-stool-structured compounds can topologically mimic phenyl rings in pharmaceuticals and contribute to the establishment of the [CpM­(CO) 3 ] core as an effective tool in the development of targeted radiotracers. , …”

Melanocortin‐1 receptor‐targeting with radiolabeled cyclic α‐melanocyte‐stimulating hormone analogs for melanoma imaging

“…Despite that, most of the 99m Tc‐radiopharmaceuticals in clinical use have the metal in the (V) oxidation state and contain the core [ 99m Tc(O)] 3+ . More recently, the remarkable features presented by the organometallic precursor fac ‐[M(CO) 3 (H 2 O) 3 ] + (M = Re(I), Tc(I)), introduced by Alberto et al18, 19 brought renewed interest to the design of innovative low‐oxidation 99m Tc‐based compounds. Indeed, the easy preparation of fac ‐[M(CO) 3 (H 2 O) 3 ] + directly from [MO 4 ] − , the lability of the three water molecules and the chemical robustness of the fac ‐[M(CO) 3 ] + unit opened new avenues for the design of innovative Tc(I)‐specific radiopharmaceuticals.…”

Direct Synthesis of Rhenium and Technetium-99m Metallosurfactants by a Transmetallation Reaction of Lipophilic Groups: Potential Applications in the Radiolabeling of Liposomes

“…This reaction has been previously reported, and it can lead to Tc-99m compounds with similar quantitative yields in the usual conditions for the preparation of radiopharmaceutical compounds. , A relevant point of this reaction, which has been mentioned above, is that the preparation of Tc-99m compounds for radiopharmaceutical purposes should be carried out at a very low metal concentration (10 –7 –10 –8 M) . Furthermore, the Tc-99m precursor used in this reaction was the cation [ 99m Tc­(H 2 O) 3 (CO) 3 ] + , a species that is considered a synthon for the preparation of Tc-99m radiopharmaceuticals as it contains Tc­(I) stabilized by three inert carbonyl ligands and three labile water molecules, which can be easily substituted by other ligands. , Hence, the one-pot 2 + 1 transmetallation reaction between the cation [ 99m Tc­(CO) 3 (H 2 O)] + , ZnC, the polar phosphine TPPTS and SPC leads to the target liposomes labeled with Tc-99m, as shown in Scheme . The reaction was performed under sonication to favor solubilization of ZnC in water, and it was completed in 30 min, a sufficiently short time that makes it possible to apply this approach for radiopharmaceutical purposes.…”

“…1 Furthermore, the Tc-99m precursor used in this reaction was the cation [ 99m Tc(H 2 O) 3 (CO) 3 ] + , a species that is considered a synthon for the preparation of Tc-99m radiopharmaceuticals as it contains Tc(I) stabilized by three inert carbonyl ligands and three labile water molecules, which can be easily substituted by other ligands. 42,43 Hence, the onepot 2 + 1 transmetallation reaction between the cation [ 99m Tc(CO) 3 (H 2 O)] + , ZnC, the polar phosphine TPPTS and SPC leads to the target liposomes labeled with Tc-99m, as shown in Scheme 6. The reaction was performed under sonication to favor solubilization of ZnC in water, and it was completed in 30 min, a sufficiently short time that makes it possible to apply this approach for radiopharmaceutical purposes.…”