1,721,004 research outputs found
Chelating Systems for 99mTc/188Re in the Development of Radiolabeled Peptide Pharmaceuticals
No full textReactivity of the [M(PS)2]+Building Block (M = ReIIIand99mTcIII; PS = Phosphinothiolate) toward Isopropylxanthate and Pyridine-2-thiolate
No full textThe coordination properties of isopropylxanthate (i-Pr-Tiox) and pyridine-2-thiolate (PyS) toward the [M(PS)(2)](+) moiety (M = Re and Tc-99m; PS = phosphinothiolate) were investigated. Synthesis and full characterization of [Re(PS2)(2)(i-Pr-Tiox)] (Re1), [Re(PSiso)(2)(i-Pr-Tiox)] (Re2), [Re(PS2)(2)(PyS)] (Re3), and [Re(PSiso)(2)(PyS)] (Re4), where PS2 = 2-(diphenylphosphino)ethanethiolate and PSiso = 2-(diisopropylphosphino)ethanethiolate, and the structural X-ray analysis of complex Re3 were carried out. Tc-99m analogues of complexes Re2 ((99m)Tc2) and Re4 ((99m)Tc4) were obtained in high radiochemical yield following a simple one-pot procedure. The chemical identity of the radiolabeled compounds was confirmed by chromatographic comparison with the corresponding rhenium complexes and by dual radio/UV HPLC analysis combined with ESI(+)-MS of 99g/Tc-99m complexes prepared in carrier-added conditions. The two radiolabeled complexes were stable with regard to trans chelation with cysteine, glutathione, and ethylenediaminotetraacetic acid and in rat and human sera. This study highlights the substitution-inert metal-fragment behavior of the [M(PS)(2)](+) framework, which reacts with suitable bidentate coligands to form stable hexacoordinated asymmetrical complexes. This feature makes it a promising platform on which to develop a new class of Re/Tc complexes that are potentially useful in radiopharmaceutical applications
Electrochemistry of oxo-technetium(V) complexes containing Schiff base and 8-quinolinol ligands
No full textThe electrochemistry of six-coordinate, monooxo technetium(V) complexes containing Schiff base ligands has been studied inacetonitrile and N,N'-dimethylformamide solutions. The complexes have the general formula TcOCl(LB)Z or TcO(L,)(L& whereLB represents a bidentate-N,O Schiff base ligand or a bidentate-N,O 8-quinolinol ligand and LT represents a tridentate-O,N,OSchiff base ligand. Cyclic voltammetry at a platinum-disk electrode, controlled-potential coulometry, and thin-layer spectroelectrochemistrywere used to probe both the oxidation and the reduction of these complexes. The results of these studies, andpreviously reported results on the analogous Re(V) complexes, can be understood within a single general reaction scheme. Thesalient features of this scheme are (i) one-electron reduction of Tc(V) to Tc(IV), (ii) subsequent loss of a ligand situated cis tothe Tc=O linkage, and (iii) subsequent isomerization of this unstable Tc(IV) product to a more stable complex in which the sitetrans to the Tc=O linkage is vacant. The Tc(IV) complexes can also be reduced to analogous Tc(II1) species, which appear toundergo the same ligand loss and isomerization reactions. The technetium complexes are 400-500 mV easier to reduce than aretheir rhenium analogues. The 8-quinolinol ligands, and especially the 5-nitro derivative, both thermodynamically and kineticallystabilize the Tc(IV) and Tc(II1) oxidation states. These electrogenerated species are unusual in that they constitute the bulk of the known examples of monomeric Tc(IV) and Tc(II1) complexes containing only N- and 0-donating ligands
Electrochemistry of rhenium(V) complexes with N-(2-hydroxyphenyl)salicylideneiminate as schiff base ligand
No full textThe anodic and cathodic behaviour of the rhenium(V) complexes nBu4N[ReOCl3(HOPhSal)], nBu4N[ReOCl2(OPhSal)], [ReOCl(OPhSal)(MeOH)] and [ReOCl(OPhSal)(PMe2Ph)] in acetonitrile was studied using platinum and mercury electrodes. Cyclic voltammetry and controlled potential coulometry were the main electroanalytical techniques employed. The nature of the electrolysis products as well as the mechanisms of the electrode oxidation and reduction processes were investigated. In particular a complex of rhenium(VI) containing the group ReO4+ and complexes of rhenium(IV) with ReO2+ core were electrochemically synthesized. They were characterized by elemental analysis, IR spectroscopy, magnetic susceptibility and conductivity measurements
Electrochemistry of rhenium(V) complexes with bidentate-bidentate and tridentate-bidentate schiff base ligands
No full textThe cathodic and anodic behaviour of rhenium(V) complexes, characterized by the ReO3+ core, with bidentate and tridentate Schiff base ligands, has been studied in acetonitrile solvent. Cyclic voltammetry and controlled potential coulometry were the main electroanalytical techniques employed to define the electrode processes. Electrolyses were also carried out with the aim to identify the nature of the reduced and oxidized products. In particular, it was possible to isolate and characterize new rhenium(VI) complexes, containing the group ReO4+, and the possibility of obtaining stable rhenium(IV) complexes has also been proved
Voltammetric behaviour of rhenium(I) complexes with phosphine and carbon monoxide ligands in acetonitrile solvent
No full textReacting Re(CO)5Cl with the azopyridine ligand (1) (L) in boiling benzene afford the complex Re(CO)3Cl(L), (2) in excellent yield [L=2-(p-Cl-C6H4NN)C5H4N]. The chelation of the azopyridine ligand accompanied by displacement of the two carbon monoxide ligands furnish a five-membered chelate ring. Structure determination of complex (2) has revealed a distorted octahedral ReC3N2Cl coordination sphere. The Re–N(pyridine) and, Re–N(azo) distances are 2.158(3) and 2.153(6) Å respectively, and the N–N length [1.273(4) Å], implicate relatively weak Re-azo(π*) back–bonding. The Re(CO)3Cl(L) lattice consists of C–H...Cl hydrogen bonding and Cl...O non-bonded interactions constituting a supramolecular network. Extended Hückel calculations reveal that the LUMO of Re(CO)3Cl(L) is Ca. 57% azo in character. One-electron quasireversible electrochemical reduction of the complex occurs near −0.3 V versus Saturated Calomel electrode(s.c.e.) The redox orbital is believed to belong to the above noted LUMO. Electrogenerated Re(CO)3Cl(L•–) underwent spontaneous solvolytic chloride displacement in MeCN, resulting in the isolation of Re(CO)3(MeCN)(L•–). The latter complex in turn reacted with imidazole and triphenylphosphine, furnishing Re(CO)3(C3H4N2)(L•–) and Re(CO)3(PPh3)(L•–), respectively. The pattern of carbonyl stretching frequencies of these radical anion complexes is similar to that of Re(CO)3Cl(L) but with shifts to lower frequencies by 10–20 cm−1. All three radical anion systems are one-electron paramagnetic (1.7–1.8 μB). The unpaired electron is primarily localized on the azoheterocycle ligand in a predominantly azo-π* orbital, but a small metal contribution (185, 187Re, I=5/2) is also present. Thus Re(CO)3(MeCN)(L•–) and Re(CO)3(C3H4N2)(L•–) display six-line e.p.r. spectra (A ̃ 28 G). The line shapes and intensities are characteristic of the presence of g-strain. In the case of Re(CO)3(PPh3)(L•–) seven nearly equispaced lines are observed due to virtually equal coupling between the metal and 31P (I=&frac;) nuclei. The g-values of the radical species are slightly higher than the free-electron value of 2.0023
Insights into the failure of the potential, neutral myocardial imaging agent TcN-NOET: physicochemical identification of by-products and degradation species
No full textIntroduction: The neutral complex [Tc-99m(N)(NOEt)(2)], often referred to as TcN-NOET [NOEt=N-ethoxy,N-ethyldithiocarbamate(1-)], was proposed several years ago as a myocardial imaging agent. Despite some favorable clinical properties evidenced during phase I and phase II studies, the overall results of the European and American phase III clinical studies have been judged insufficient for a successful approval process by the regulatory agencies.
Methods: Non-carrier-added and carrier-added experiments using short-lived Tc-99m and long-lived Tc-99g have been utilized to prepare a series of bis-substituted [Tc(N)(DTC)(2)] complexes [DTC=dithiocarbamate(1-)]. They have been purified by means of chromatographic techniques (high-performance liquid chromatography and thin-layer chromatography) and identified via double detection (UV-vis and radiometry) by comparison with authenticated samples of Tc-99g compounds prepared by conventional coordination chemistry procedures.
Results: The molecular structure of the lipophilic, neutral complex cis-[Tc(N)(NOEt)(2)] has been assigned by comparison with similar nitrido-Tc(V) complexes already reported in the literature. Novel bis-substituted nitrido-Tc complexes containing hydrolyzed portions of coordinated NOEt, namely, N-ethyldithiocarbamate [NHEt(1-)] and N-hydroxy, N-ethyldithiocarbamate [NOHEt(1-)], have been prepared and characterized by means of multinuclear nuclear magnetic resonance spectroscopy and mass spectrometry.
Conclusions: Despite the identification of these "hydrolyzed" species, it is still unclear whether the failure to reach the clinical goal of the perfusion tracer [Tc-99m(N)(NOEt)(2)] is related to the degradation processes evidenced in this study or is the result of the mediocre imaging properties of the tracer. (C) 2012 Elsevier Inc. All rights reserved
Novel [99mTcIII(PS)2(Ln)] Mixed-Ligand Compounds (PS = Phosphino-thiolate; L = Dithiocarbamate) Useful in Design and Development of TcIII-Based Agents: Synthesis, in Vitro, and ex Vivo Biodistribution Studies
No full textA general procedure for the preparation of a new class of neutral six-coordinated mixed ligand [(99m)Tc(III)(PS)2(Ln)] compounds (PS = trisalkyl-phosphino-thiolate; Ln = dithiocarbamate) is reported as well as their in vitro stability and the ex vivo tissue distribution studies. [(99m)Tc(PS)2(Ln)] complexes were prepared in high yield in nearly physiologic conditions following a one-pot procedure. For instance, the chemical identity of [(99m)Tc(PSiso)2(L1)] (PSiso = 2-(diisopropylphosphino)ethanethiol; L1 = pyrrolidine dithiocarbamate) was determined by HPLC comparison with the corresponding (99g)Tc-complex. All complexes comprise the stable [(99m)Tc(III)(PS)2](+) moiety, where the remaining two coordination positions are saturated by a dithiocarbamate chelate, also carrying bioactive molecules (e.g., 2-methoxyphenylpiperazine). [(99m)Tc(PS)2(Ln)] complexes were inert toward ligand exchange reactions. No significant in vitro and in vivo biotransformation were observed, underlining their remarkable thermodynamic stability and kinetic inertness. These results could be conveniently utilized to devise a novel class of (99m)Tc(III)-based compounds useful in radiopharmaceutical applications
Synthesis, characterization and biological evaluation of [188Re(N)(cys-)(PNP)]+/0 mixed-ligand complexes as prototypes for the development of 188Re(N)-based target-specific radiopharmaceuticals
No full textWe report on an efficient procedure for the preparation of [Re-188(N)(PNP)]-based complexes (where PNP is diphosphinoamine) useful in the development of target-specific radiopharmaceuticals. The radiochemical yield of the compounds was optimized considering such reaction parameters as nature of the nitrido nitrogen donor, reaction times and pH level. The chemical identity of the Re-188 agents was determined by high-performance liquid chromatography comparison with the corresponding well-characterized cold Re compounds. Re-188(N) mixed compounds have been evaluated with regard to stability toward transchelation with GSH and degradation by serum enzymes. The clearance of selected radiocompounds from normal tissues and their in vivo stability were evaluated in rats by biodistribution and imaging studies. [Re-188(N)(cys similar to)(PNP)](+/0) mixed-ligand compounds were efficiently prepared in aqueous solution from perrhenate using a multistep procedure based on the preliminary formation of the labile Re-188(III)-EDTA species, which easily undergo oxidation/ligand exchange reaction to afford the [Re-188(V) N](2+) core in the presence of dithiocarbazate. The final mixed-ligand compounds were obtained, at 100 degrees C, by adding the two bidentate ligands to the buffered [(ReN)-Re-188-N-V ](2+) solution (pH 3.2-3.6). However, a relatively high amount of cys similar to ligand was required to obtain a quantitative radiochemical yield. The complexes were stable toward reoxidation to perrhenate and ligand exchange reactions. In vivo studies showed rapid distribution and elimination of the complexes from the body. No specific uptakes in sensitive tissues/organs were detected. A positive correlation of the distribution of the complexes estimated with biodistribution studies (%ID) and with micro-SPECT semiquantification imaging analysis (standard uptake values) was observed. These results support the possibility of applying [Re-188(N)(PNP)] technology to the preparation of target-specific agents. (C) 2011 Elsevier Inc. All rights reserved
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