Chemistry of the Strong Electrophilic Metal Fragment [⁹⁹Tc(N)(PXP)]²⁺ (PXP = Diphosphine Ligand). A Novel Tool for the Selective Labeling of Small Molecules

Abstract

Monosubstituted [M(N)Cl(2)(POP)] [M = Tc, 1; Re, 2] and [M(N)Cl(2)(PNP)] [M = Tc, 3; Re, 4] complexes were prepared by reaction of the precursors [M(N)Cl(4)](-) and [M(N)Cl(2)(PPh(3))(2)] (M = Tc, Re) with the diphosphine ligands bis(2-diphenylphosphinoethyl)ether (POP) and bis(2-diphenylphosphinoethyl)methoxyethylamine (PNP) in refluxing dichloromethane/methanol solutions. In these compounds, the diphosphine acted as a chelating ligand bound to the metal center through the two phosphorus atoms. Considering also the weak interaction of the heteroatom (N or O) located in the middle of the carbon backbone connecting the two P atoms, we found that the coordination arrangement of the diphosphine ligand could be viewed as either meridional (m) or facial (f), and the resulting geometry as pseudooctahedral. The heteroatom of the diphosphine ligand was invariably located trans to the nitrido linkage, as established by X-ray diffraction analysis of the representative compounds 2m and 4f. Density functional theoretical calculations showed that in POP-type complexes the mer form is favored by approximately 6 kcal mol(-1), whereas mer and fac isomers are almost isoenergetic in PNP-type complexes. A possible role of noncovalent interactions between the phosphinic phenyl substituents in stabilizing the fac-isomer was also highlighted. The existence of fac-mer isomerism in this class of complexes was attributed to the strong tendency of the two phosphorus atoms to occupy a reciprocal trans-position within the pseudooctahedral geometry. The switching of P atoms between cis- and trans-configurations was confirmed by the observation that the fac isomers, 1f and 2f, were irreversibly transformed, in solution, into the corresponding mer isomers, 1m and 2m, thus suggesting that fac complexes are more reactive species. Theoretical calculations supported this view by showing that the lowest unoccupied orbitals of the fac isomers are more accessible to a nucleophilic attack with respect to those of the mer ones. Furthermore, the large participation of the Cl orbitals to the HOMO, which is a metal-ligand pi* antibonding in the complex basal plane, shows that the Tc-Cl bonds are labile. As a consequence, facial isomers could be considered as highly electrophilic intermediates that were selectively reactive toward substitution by electron-rich donor ligands. Experimental evidence was in close agreement with this description. It was found that fac-[M(N)Cl(2)(PXP)] complexes easily underwent ligand-exchange reactions with bidentate donor ligands such as mercaptoacetic acid (NaHL(1)), S-methyl 2-methyldithiocarbazate (H(2)L(2)), diethyldithiocarbamate sodium salt (NaL(3)), and N-acetyl-L-cysteine (H(2)L(4)) to afford stable asymmetrical heterocomplexes of the type fac-[M(N)(L(n))(POP)](+/0) (5-8) and fac-[M(N)(L(n))(PNP)](+/0) (9-14) comprising two different polydentate chelating ligands bound to the same metal center. In these reactions, the bidentate ligand replaced the two chloride atoms on the equatorial plane of the distorted octahedron,...

Synthesis, Solution‐State and Solid‐State Structural Characterization of Monocationic Nitrido Heterocomplexes [M(N)(DTC)(PNP)]+ (M = 99Tc, Re; DTC = Dithiocarbamate; PNP = Heterodiphosphane)

“…As previously noted for the similar com- [7] the remarkable stability of this class of complexes results from a balance of π-acceptor and π-donor properties provided by the combination of the diphosphane and dithiocarbamate ligands bound to the same [MϵN] 2ϩ group. 2ϩ .…”

“…The ReϵN(1) distance of 1.660(9) Å is close to the average of 1.675 Å found for terminal nitride-Re V compounds (29 entries in the Cambridge Structural Database [15] . [7] The S(1)ϪReϪS (2) (11) atoms. The methylene carbons of the diphosphane chain, C(1), C(4), C(2), and C(3), are located, respectively, at 1.69, 1.81, 2.64 and 2.64 Å below the mean S 2 P 2 basal plane, whereas N(2) faces this plane at the intermediate distance of 2.29 Å .…”

“…Examples of this specific class include the low-valent aqua-carbonyl [Tc I (CO) 3 (OH 2 ) 3 ] ϩ complex [4,5] and high-valent, nitrido-diphosphane [Tc(N)(PNP)Cl 2 ] complexes. [6,7] In these complexes, the [Tc(CO) 3 ] ϩ and [Tc(N)(PNP)] 2ϩ fragments are the stable molecular units. In contrast, the water and halide ϩ FULL PAPER ligands can be efficiently substituted by a series of bi-functional tridentate σ-donor ligands (L) and bidentate π-donor ligands (LЈ), respectively, to yield mixed heterocomplexes of the type [Tc(CO) 3 …”

Metal-dithiocarbamate complexes: chemistry and biological activity

“…Related cationic complexes such as 99m Tc-DBODC5 (Fig. 11c) [115] are also under investigation and have been shown to have much better liver clearance (Fig. 11).…”

New SPECT and PET Radiopharmaceuticals for Imaging Cardiovascular Disease

“…Bolzati et al investigated a novel series of cationic 99m Tc-nitrido complexes containing a [ 99m Tc ≡ N] 2+ -core with a bidentate dithiocarbamate (DTC) and tridentate PNP-type bisphosphine chelates [30]. One example is the 99m Tc-nitrido complex DBODC5 ( 99m Tc-[bis (dimethoxypropylphosphinoethyl)-methoxyethylamine (PNP5)]-[bis (N-ethoxyethyl)-dithiocarbamate (DBODC)] nitride (N-PNP5-DBODC or N-DBODC5) (Table 2), which demonstrated high cardiac uptake and retention for more than 2 hours and nearly complete elimination of hepatocyte activity by two hours in Sprague-Dawley (SD) rats [31, 32].…”