Syntheses and radiolabeling of cysteine-oximes and pharmacological behaviour of their 99mTc complexes (original) (raw)
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JBIC Journal of Biological Inorganic Chemistry, 2001
Novel oxorhenium and oxotechnetium complexes based on the tetradentate 1-(2-hydroxybenzamido)-2-(pyridinecarboxamido)benzene, H 3 L, ligand have been synthesized and characterized herein. Thus, by reacting equimolar quantities of the triply deprotonated ligand L 3± with the suitable MO 3+ precursor, the following neutral MOL complexes could be easily produced following similar synthetic routes: M=Re (1), M= 99g Tc (2), and M= 99m Tc (3). Complexes 1 and 2, prepared in macroscopic amounts, were chemically characterized and their structure determined by singlecrystal X-ray analysis. They are isostructural metal chelates, adopting a distorted square pyramidal geometry around the metal. The N 3 O donor atom set of the tetradentate ligand defines the basal plane and the oxygen atom of the M=O core occupies the apex of the pyramid. Complex 3 forms quantitatively at tracer level by mixing the H 3 L ligand with Na 99m TcO 4 generator eluate in aqueous alkaline media and using tin chloride as reductant in the presence of citrate. Its structure was established by chromatographic comparison with prototypic complexes 1 and 2 using high-performance liquid chromatographic techniques. When challenged with excess glutathione in vitro, complex 3 is rapidly converted to hydrophilic unidentified metal species. Tissue distribution data after administration of complex 3 in vivo revealed a significant uptake and retention of this compound in brain tissue.
Sys Rev Pharm, 2020
The ligand Schiff base [(E)-3-(2-hydroxy-5-methylbenzylideneamino)-1-phenyl-1H-pyrazol-5(4H)-one] with some metals ion as Mn(II); Co(II); Ni(II); Cu(II); Cd(II) and Hg(II) complexes have been preparation and characterized on the basic of mass spectrum for L, elemental analyses, FTIR, electronic spectral, magnetic susceptibility, molar conductivity measurement and functions thermodynamic data study (∆H°, ∆S° and ∆G°). Results of conductivity indicated that all complexes were non electrolytes. Spectroscopy and other analytical studies reveal distorted octahedral geometry for all complexes. The antibacterial activity of the ligand and preparers metal complexes was also studied against gram and negative bacteria.
13 and 14membered macrocyclic ligands containing methylcarboxylate J Inorg Biochem 2006
2013
The stability constants of La 3+ , Sm 3+ and Ho 3+ complexes with 13-and 14-membered macrocycles having methylcarboxylate (trita and teta) or methylphosphonate (tritp and tetp) arms were determined. All the ligands were labelled with 153 Sm and 166 Ho in order to evaluate the effect of the macrocyclic cavity size and type of appended arms on their in vitro and in vivo behaviour. The radiolabelling efficiency was found to be higher than 98% for all the complexes, except for those of tetp. All radiocomplexes studied are hydrophilic with an overall negative charge and low plasmatic protein binding. Good in vitro stability in physiological media and human serum was found for all complexes, except the 153 Sm/ 166 Ho-teta, which are unstable in phosphate buffer (pH 7.4). In vitro hydroxyapatite (HA) adsorption studies indicated that 153 Sm/ 166 Ho-tritp complexes bind to HA having the 166 Ho complex the highest degree of adsorption (>80%, 10 mg). Biodistribution studies in mice demonstrated that 153 Sm/ 166 Ho-trita complexes have a fast tissue clearance with more than 95% of the injected activity excreted after 2 h, value that is comparable to the corresponding dota complexes. In contrast, the 153 Sm-teta complex has a significantly lower total excretion. 153 Sm/ 166 Ho-tritp complexes are retained by the bone, particularly 166 Ho-tritp that has 5-6% (% I.D./g) bone uptake and also a high rate of total excretion. Thus, these studies support the potential interest of 153 Sm/ 166 Ho-trita complexes for therapy when conjugated to a biomolecule and the potential usefulness of the 166 Ho-tritp complex in bone pain palliation.
ChemistrySelect, 2017
The '4 + 1' mixed ligand strategy enables radiolabeling of biomolecules with 99m Tc at low ligand concentration without affecting it's in vivo biological activity. The '4 + 1' mixed-ligand complexes consist of central Tc(III) metal atom coordinated to a tetradentate tripodal chelator 2,2',2''-nitrilotriethanethiol (NS 3) and a monodentate isocyanide group tethered to a biomolecule. The present work describes the use of '4 + 1' mixed ligand strategy to design radiopharmaceuticals for the detection of tissue hypoxia in vivo. Isocyanide derivatives of two nitroimidazoles, viz. 2-nitroimidazole (2NimNC) and metronidazole (MetNC), were synthesized and radiolabeled with 99m Tc using '4 + 1' mixed ligand approach. The complexes [ 99m Tc(NS 3)(2NimNC)] and [ 99m Tc(NS 3)(MetNC)] could be prepared in excellent yield (> 90%). The structure of 99m Tc-complexes prepared at the no-carrier-added (nca) level was corroborated by spectroscopic analysis of corresponding rhenium analogues at the macroscopic level. Preliminary biological evaluation of the two nitroimidazole-'4 + 1' mixed ligand complexes in Swiss mice bearing fibrosarcoma tumor showed uptake and retention of the complexes in tumor.
Journal of Biophysical Chemistry, 2011
A [ReO(Imz)(Hyd)(H 2 O) 2 OH] complex was successfully synthesized by the ligand exchange method using oxorhenuim citrate and an imidazole /Hydanton mixed ligand system. Geometry optimization of complex has been carried out using DFT at the B3LYP/LANL2DZ functional in singlet state. B3LYP predicated infrared spectrum of the geometrically optimized structure using the same level of the theory and the same base set showed good agreement with experimentally observed values. The spin allowed singlet-singlet electronic transition of the [ReO(Imz)(Hyd) (H 2 O) 2 OH] complex was calculated with time dependent density function theory (TD-DFT) and the UV-Vis spectra has been discussed on this basis. The complex was characterized using microanalysis and IR, UV-Vis, NMR and mass spectroscopic. The technetium tracer [ 99m TcO(Imz)(Hyd) (H 2 O) 2 OH] has also been synthesized by two methods using 99m Tc-gluconate as a precursor or; by direct reduction. The radiochemical purity of the complex was over 95% as measured by thin layer chromatography. In vitro studies showed that the complex possessed good stability under physiological conditions. The partition coefficient indicated that the complex hydrophilic and the electrophoresis results showed that the complex cationic. Biodistrbution in mice showed that the complex accumulated in heart uptake of 9.53 ± 3.87% ID/gm at 5 min and good retention (6.37 ± 1.21)% ID/gm at 60 min. One hour after the injection, the heart/liver, heart/lung and heart/blood radioactivity ratios were 0.46, 1.04 and 0.56, respectively. These findings indicate that the complex might be suitable for myocardial imaging.
Preparation, Spectroscopic, Bioactive and Theoretical Studies of Mixed Ligand Complexes
Journal of Al-Nahrain University - Science, 2017
The mixed ligands complexes of 8-hydroxyquinoline and Schiff base 1, 5-dimethyl-4-(5oxohexan-2-ylideneamino)-2-phenyl-1H-pyrazol-3 (2H)-one (L) with Cr (III) , Mn (II) , Fe (II) , Co (II) , Ni (II) , Cu (II) and Zn (II) ions were prepared. The compounds have been characterized by NMR, FT-IR, UV-Vis and mass spectra, elemental microanalysis (C.H.N.), magnetic moment, chloride contain, atomic absorption and molar conductance. All prepared complexes were octahedral geometry. Compound structures treated theoretically using the program hyper chem. 8 in gas phase at 298°K. The compounds were also screened for their bioactive property such as antifungal and antibacterial.
New Journal of Chemistry, 2010
The present paper deals with the synthesis and characterization of metal complexes of Schiff base derived from xipamide, a diuretic drug. The bidentate ligand is derived from the inserted condensation of 5-aminosulfonyl-4-chloro-N-2,6-dimethyl phenyl-2-hydroxybenzamide (Xipamide) with salicylaldehyde in a 1 : 1 molar ratio. Using this bidentate ligand, complexes of Hg(II), Zn(II), and VO(IV) with general formula ML 2 have been synthesized. The synthesized complexes were characterized by several techniques using molar conductance, elemental analysis, magnetic susceptibility, FT-IR spectroscopy, electronic spectra, mass spectra, and particle size analysis. The elemental analysis data suggest the stoichiometry to be 1 : 2 [M : L]. All the complexes are nonelectrolytic in nature as suggested by molar conductance measurements. Infrared spectral data indicate the coordination between the ligand and the central metal ion through deprotonated phenolic oxygen and azomethine nitrogen atoms. Spectral studies suggest tetrahedral geometry for Hg(II), Zn(II) complexes, and square pyramidal geometry for VO(IV) complex. The pure drug, synthesized ligand, and metal complexes were screened for their antifungal activities against Aspergillus niger and Aspergillus flavus. The ligand and its Hg(II) and VO(IV) complexes were screened for their diuretic activity too.