L. Kaden

Bio: L. Kaden is an academic researcher. The author has contributed to research in topics: Electron paramagnetic resonance. The author has an hindex of 1, co-authored 3 publications receiving 47 citations.

Nitrido Complexes of Technetium with Tertiary Phosphines and Arsines.

Abstract: Diamagnetic Technetium(V) complexes of general formulae [TcNX 2 (Ph 3 Y) 2 ] and [TcNX 3 (Me 2 PhP) 3 ] (X = Cl, Br; Y = P, As) were prepared starting from TcNCl 4 − and TcNBr 4 − , respectively and were characterized. Ligand exchange rates with diethyldithiocarbamate, et 2 dtc − and N-(N″-morpholinylthiocarbonyl)benzamidinate, morphtcb − , were determined.

Chemistry of the strong electrophilic metal fragment [(99)Tc(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, leaving the starting fac-[M(N)(PXP)](2+) (X = O, N) moieties untouched. No formation of the corresponding symmetrical complexes containing two identical bidentate ligands was detected over a broad range of experimental conditions. Solution-state NMR studies confirmed that the structure in solution of these heterocomplexes was identical to that established in the solid state by X-ray diffraction analysis of the prototype complexes fac-[M(N)(HL(2))(POP)][BF(4)] [M = Tc, 7; Re, 8] and fac-[Tc(N)(HL(2))(PNP)][BF(4)], 11. In conclusion, the novel metal fragment fac-[M(N)(PXP)](2+) could be utilized as an efficient synthon for the preparation of a large class of asymmetrical, nitrido heterocomplexes incorporating a particular diphosphine ligand and a variety of bidentate chelating molecules.

Synthesis and Biologic Evaluation of Monocationic Asymmetric 99mTc-Nitride Heterocomplexes Showing High Heart Uptake and Improved Imaging Properties

Abstract: The preparation, characterization, and first biologic evaluation in rats of a novel class of monocationic 99mTc heart imaging agents are reported. The complexes are represented by the general formula [99mTc(N)(PNP)(L)]+, where L is the monoanionic form of a dithiocarbamate ligand of the type [R1(R2)-N-C(=S)S]−, PNP is a diphosphine ligand of the type [(R3)2P-(CH2)2]2-N(R4), and R1–R4 are organic functional groups. Methods: The new complexes were prepared by use of both liquid and freeze-dried formulations through a 2-step procedure. The first step involved the formation of the [Tc≡N]2+ group through the reaction of 99mTcO4− with succinic dihydrazide as a donor of nitride nitrogen atoms (N3−) in the presence of Sn2+ ions. This step was followed by the simultaneous addition to the reaction solution of the ligand PNP and of the sodium salt of the dithiocarbamate ligand (NaL) to afford the final products, [99mTc(N)(PNP)(L)]+. The chemical identities of the resulting 99mTc complexes were determined by comparing their chromatographic properties with those of the corresponding 99gTc analogs prepared by use of the long-lived isotope 99gTc and characterized by spectroscopic and crystallographic techniques. Ex vivo biodistribution studies were conducted in rats. In vivo tomographic images of the rat heart were obtained by use of a small-animal SPECT scanner. Results: The [99mTc(N)(PNP)(L)]+ complexes are monocationic and possess a distorted square-pyramidal geometry in which the Tc≡N multiple bond occupies an apical position and the diphosphine and dithiocarbamate ligands span the residual 4 coordination positions on the basal plane through the 2 phosphorus atoms and the 2 sulfur atoms, respectively. Imaging and biodistribution studies demonstrated that these radiopharmaceuticals localize selectively in the myocardium of rats and are retained in this region for a prolonged time. The kinetics of heart uptake and clearance were found to be influenced by variations in the lateral R1–R4 groups. Blood and lung washouts were extremely fast. Elimination occurred mostly through the kidneys and the liver. Surprisingly, at 1 h after injection, liver activity was almost negligible. Analysis of heart-to-liver and heart-to-lung uptake ratios showed that these values increased exponentially over time and became much higher than those determined for 99mTc-sestamibi and 99mTc-tetrofosmin. These findings were confirmed by analysis of high-quality SPECT images collected in rats for the new complexes and compared with images obtained with 99mTc-sestamibi and 99mTc-tetrofosmin. Conclusion: The high myocardial uptake and the very high heart-to-lung and heart-to-liver uptake ratios indicate that the [99mTc(N)(PNP)(L)]+ complexes exhibit very favorable distribution properties and could be used to obtain SPECT cardiac images with improved quality.

Synthon for Use with Biologically Active Molecules. The N-(2-Methoxyphenyl)piperazyl-cysteine Analogues as Examples

Abstract: The incorporation of a bioactive molecule into a nitrido-containing 99m Tc-complex has been successfully achieved by using the [TcN(PNP)] 2+ metal fragment. In this strategy, the strong electrophilic [TcN(PNP)] 2+ metal fragment efficiently reacts with bifunctional chelating ligands having a ﷿-donor atom set, such as N-functionalized O,S-cysteine. The 2-methoxyphenylpiperazine (2-MPP) pharmacophore, which displays preferential affinity for 5HT1A receptors, was conjugated to the amino group of cysteine to obtain 2-MPPP-cys-OS, where 2-MPPP is 3-[4-(2-methoxyphenyl)piperazin-1-yl]propionate. The asymmetric Tc(V)-nitrido complexes, [ 99g/99m Tc(N)(PNP)(2-MPPP-cys-OS)] (PNP ) PNP3, PNP4), were obtained in high yield (95%), by simultaneous addition of PNP and 2-MPPP-cys-OS ligand to a solution containing a starting 99g / 99m Tc-nitrido precursor. A mixture of syn and anti isomers was observed, the latter being the thermodynamically favored species. In vitro challenge experiments using the anti isomers with glutathione and cysteine indicated that no transchelation reaction occurs. Assessment of the in vitro 5HT1A receptor-affinity of the technetium complexes revealed that only the anti-PNP4 complex possesses some affinity for the receptor, but displayed negligible brain uptake in biodistribution studies in rats in vivo.

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

Abstract: Mono-cationic nitrido heterocomplexes of general formula [M(N)(DTC)(PNP)]+ (where M is 99Tc or Re, DTC is the mono-anionic form of a dithiocarbamate ligand, and PNP is a diphosphane ligand with a tertiary amine-containing five-membered spacer) were prepared by ligand-exchange reactions with the labile precursors [M(N)Cl2(PPh3)2] in dichloromethane/alcohol mixtures. The molecular structure of the representative rhenium complex [Re(N)(dedc)(pnp2)][PF6] (1) displays a distorted, square-pyramidal geometry with the dithiocarbamate sulfur and the diphosphane phosphorus atoms spanning the four coordination positions on the equatorial plane. If the additional interactions between the nitrido nitrogen and the weakly bonded transN-diphosphane heteroatom, the molecular geometry can be viewed as pseudo-octahedral. The structure in solution, as established by multinuclear NMR spectroscopy and ESI spectrometry, is monomeric, and identical to that shown in the solid state. Replacement of the phenyl groups on the phosphorous atoms in complexes 1, 2, 5, and 6 with alkyl groups modified neither the course of the reaction nor the composition of the resulting complexes. These results, together with the observation that no symmetrical complexes containing two identical bidentate ligands were produced in these reactions, strongly supports the conclusion that a mixed coordination sphere, composed by a combination of π-donor and π-acceptor atoms around the [M≡N]2+ group, constitutes a highly stable system. Compounds containing dangling alkyl-substituted groups in the outer sphere (3, 4, 7, and 8) were fully characterized by multinuclear NMR spectroscopy and ESI mass spectrometry. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

The Coordination Chemistry of Technetium

Abstract: Publisher Summary This chapter describes the coordination chemistry of technetium focusing on technetium(−I), technetium(0), technetium(I), technetium(II), technetium(III), technetium(IV), technetium(V), technetium(VI), and technetium(VII). Technetium(III) complexes with aminocarboxylato ligands have been observed but none are well characterized. 99m Tc–iminodiacetate complexes formed with 2,6-alkylphenyl [ArNHCOCH 2 N(CH 2 COO) 2 ] 2− ligands are used to image the hepatobiliary system. One of the approaches to cationic myocardial imaging agents has been the development of neutral seven-coordinate Tc(III) complexes based on 1,2-dioxime ligands (dioximeH 2 ) with one end capped by a boronic acid derivative. These complexes are generally referred to as boronic acid adducts of technetium dioximes (BATOs). The highest binary chloride of technetium is the dark red TcCl 4 formed as the major product of the chlorination of Tc metal. Crystallography reveals a polymeric chain structure of C1-bridged distorted octahedral TcCl 6 units. The structure and chemistry of the square-pyramidal five-coordinate and pseudo-octahedral six-coordinate [Tc V O] 3+ complexes are dominated by the strong tetragonal distortion induced by the multiply bonded oxo ligand.