RESUMEN
The free H(2)xspa ligands [xspa = pspa, Clpspa, tspa or fspa where p = 3-(phenyl), Clp = 3-(2-chlorophenyl), t = 3-(2-thienyl), f = 3-(2-furyl) and spa = 2-sulfanylpropenoato], their Zn(II) complexes of formula [HQ](2)[Zn(xspa)(2)] (HQ = diisopropylammonium) and the Cd(II) equivalents were prepared and characterized by elemental analysis and by IR, Raman and NMR ((1)H, (13)C) spectroscopy. X-Ray studies of the crystal structures of [HQ](2)[Zn(pspa)(2)], [HQ](2)[Zn(Clpspa)(2)], [HQ](2)[Zn(tspa)(2)] and [HQ](2)[Zn(fspa)(2)] show that the zinc atom is coordinated to two O atoms and two S atoms of the ligands in a distorted tetrahedral ZnO(2)S(2) environment. In the structures of [HQ](2)[Cd(pspa)(2)] and [HQ](2)[Cd(Clpspa)(2)] the cadmium atom is coordinated to three S atoms and two carboxylato O atoms of the ligands in a distorted trigonal bipyramidal environment. The interchange of ligands between Zn(II) and Cd(II) was studied by (113)Cd NMR spectroscopy. The in vitro protective effect of H(2)xspa and their Zn(II) complexes against Cd toxicity was investigated using the human hepatocarcinoma HepG2 cell line and the pig renal proximal tubule LLC-PK1 cell line. The incorporation of Zn(II) was found to be relevant in the case of H(2)pspa, with an increase observed in the cell viability of the LCC-PK1 cells with respect to the value for the free ligand.
Asunto(s)
Acrilatos/química , Cadmio/toxicidad , Complejos de Coordinación/química , Sustancias Protectoras/química , Zinc/química , Animales , Línea Celular , Complejos de Coordinación/síntesis química , Cristalografía por Rayos X , Células Hep G2 , Humanos , Espectroscopía de Resonancia Magnética , Conformación Molecular , Sustancias Protectoras/síntesis química , PorcinosRESUMEN
Reaction of the title ligands (HPyTSC and HS(S)PPh2, respectively) with R2SnO (R = Me, Et, Bu) in ethanol (EtOH) afforded the complexes [SnMe2(PyTSC) (S2PPh2)].EtOH (1) and [SnR2(PyTSC) (S2PPh2)] (R = Et (2), Bu (3)). The structures of 1 and 2 were determined by single-crystal X-ray diffractometry. In both these complexes the tin atom is coordinated to an N,N,S-dentate thiosemicarbazonate ligand, an anisobidentate dithiophosphinato ligand and the two R groups. The coordination polyhedrons can be described as distorted pentagonal bipyramids. A comparative study of the IR spectra of 1, 2 and 3 indicates that the butyl complex has a similar structure. Multinuclear (1H, 13C, 31P and 119Sn) NMR data suggest that the structures of 1 and 2 probably remain in CDCl3 (or DMSO-d6) solution but compound 3 partially decomposes in these media. Preliminary results on the effects of the complexes on the proliferation and differentiation of FLC, CEM, U937, K562 and TOM-1 leukaemia cells, and on the clonogenic activity of K562 cells are also described.
Asunto(s)
Compuestos Orgánicos de Estaño/química , Compuestos Orgánicos de Estaño/farmacología , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Cristalografía por Rayos X , Humanos , Células K562 , Ligandos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Compuestos Orgánicos de Estaño/síntesis química , Espectrofotometría InfrarrojaRESUMEN
The complexes [SnR2(L)] (R = Me, Et, Bu, Ph; H2L = pyridoxal thiosemicarbazone) have been prepared and characterized. In the light of the spectral properties of the complexes in the solid state (IR, mass, Mössbauer) the bideprotonated thiosemicarbazonato anion is O(phenolic)-, N(3)-, S-bonded to the tin atom which probably has trigonal bipyramidal coordination with N(3) atom and R groups occupying equatorial positions. NMR ( 1H, 13C and 119Sn) data in CDCl3 or DMSO-d6 suggest that this coordinative picture remains in these solutions. The ethyl, butyl and phenyl derivatives suppress proliferation of Friend erithroleukaemia cells (FLC). Of the pyridoxal thiosemicarbazone complexes so far evaluated. [SnBu2(L)] and [SnPh2(L)] showed the lowest thresholds for inhibition of FLC proliferation. The effects of these compounds on DMSO-induced differentiation of FLC, DNA synthesis and reverse transcriptase were also assayed.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Compuestos Orgánicos de Estaño/síntesis química , Compuestos Orgánicos de Estaño/farmacología , Piridoxal/análogos & derivados , Tiosemicarbazonas/síntesis química , Tiosemicarbazonas/farmacología , Animales , Antineoplásicos/química , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , ADN de Neoplasias/biosíntesis , Dimetilsulfóxido/farmacología , Virus de la Leucemia Murina de Friend , Leucemia Eritroblástica Aguda/tratamiento farmacológico , Leucemia Eritroblástica Aguda/metabolismo , Leucemia Eritroblástica Aguda/patología , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Ratones , Compuestos Orgánicos de Estaño/química , Piridoxal/síntesis química , Piridoxal/química , Piridoxal/farmacología , Inhibidores de la Transcriptasa Inversa/síntesis química , Inhibidores de la Transcriptasa Inversa/química , Inhibidores de la Transcriptasa Inversa/farmacología , Espectroscopía de Mossbauer , Tiosemicarbazonas/química , Células Tumorales CultivadasRESUMEN
The synthesis, X-ray structure, behavior in solution, and biological properties of the complex [SnMe2(PyTSC)(OAc)].HOAc (HPyTSC = pyridine-2-carbaldehydethiosemicarbazone) are reported. The tin atom of this complex is coordinated to an N,N,S-tridentate PyTSC- anion, to a monodentate acetate ion, and to the two methyl groups in an approximately pentagonal bipyramidal environment with a vacant equatorial position. The complex partially evolves in DMSO and in DMSO/CHxCl4-x (X = 1, 2) mixtures, giving HPyTSC and SnMe2(OAc)2. [SnMe2 (PyTSC)(OAc)].HOAc, [SnMe2(DAPTSC)], and [SnPh2(DAPTSC)].2DMF (H2DAPTSC = 2,6-diacetylpyridine bis(thiosemicarbazone)) all suppress proliferation of Friend erythroleukaemia cells (FLC). DMSO-induced differentiation of FLC is slightly suppressed by [SnMe2(DAPTSC)] and is unaffected by [SnPh2(DAPTSC)].2DMF and [SnMe2(PyTSC)(OAc)].HOAc.
Asunto(s)
Antineoplásicos/síntesis química , Compuestos Orgánicos de Estaño/síntesis química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Cristalografía por Rayos X , Virus de la Leucemia Murina de Friend , Leucemia Eritroblástica Aguda/tratamiento farmacológico , Ratones , Modelos Moleculares , Estructura Molecular , Compuestos Orgánicos de Estaño/química , Compuestos Orgánicos de Estaño/farmacología , Soluciones , Espectrofotometría Infrarroja , Células Tumorales CultivadasRESUMEN
The interaction of vitamin B6 pyridoxine with cadmium acetate in ethanolic solution has been studied. The new compound Cd(PN-H)(OOCCH3) (PN-H = pyridoxinato anion) was isolated and its structure studied in the solid state by IR and 13C and 113Cd CP/MAS NMR spectroscopies. The effect of pyridoxine on survival rate among male Sprague rats injected intraperitoneally with 5 mg CdCl2.H2O/kg was also investigated. Vitamin treatment seems to increase (Protocol C) or does not affect the cadmium lethality. Although the analysis of the metal burden in some organs seems to suggest a light increase of the cadmium level in the liver, this change has no significance at a statistical level.
Asunto(s)
Cadmio/metabolismo , Piridoxina/metabolismo , Animales , Cadmio/administración & dosificación , Cadmio/química , Cadmio/toxicidad , Cloruro de Cadmio , Cloruros/administración & dosificación , Cloruros/toxicidad , Interacciones Farmacológicas , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Piridoxina/química , Piridoxina/farmacología , Ratas , Ratas Endogámicas , Solubilidad , Espectrofotometría InfrarrojaRESUMEN
The survival rate was high among male Sprague rats treated with 0.15 mg/kg vitamin B12 (cyanocobalamine) after injection of 5 mg/kg CdCl2.H2O (LD50). The cadmium content of the liver and, for some protocols, in the kidney was significantly reduced in survivors. According to UV-V and multinuclear (1H, 13C, 31P, and 113Cd) magnetic resonance spectroscopy no direct interaction seems to take place between cyanocobalamine and CdCl2 in aqueous solution at pH 4.5. An indirect mechanism is put forward to explain the antidotal activity.
Asunto(s)
Cadmio/toxicidad , Vitamina B 12/farmacología , Animales , Cadmio/farmacocinética , Cloruro de Cadmio , Riñón/efectos de los fármacos , Riñón/metabolismo , Dosificación Letal Mediana , Hígado/efectos de los fármacos , Hígado/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Masculino , Ratas , Ratas Endogámicas , Distribución TisularRESUMEN
We report the synthesis of new complexes with the general formula (R2SnX2)y.H2BiIm, where y = 1 or 2; R = Me, Et, Bun; X = Cl or Br (for R = Et) and H2BiIm = 2,2'-Biimidazole. The complexes have been characterized by elemental analysis and Mössbauer, infra-red and 1H n.m.r. spectroscopy and tested (like the ligand, Me2SnCl2 and Et2SnCl2) against P388D1 leukemic cells.
Asunto(s)
Antineoplásicos , División Celular/efectos de los fármacos , Halógenos/farmacología , Imidazoles/farmacología , Leucemia P388/tratamiento farmacológico , Leucemia Experimental/tratamiento farmacológico , Compuestos Orgánicos de Estaño/farmacología , Animales , Fenómenos Químicos , Química , Halógenos/síntesis química , Imidazoles/síntesis química , Espectroscopía de Resonancia Magnética , Ratones , Ratones Endogámicos DBA , Compuestos Orgánicos de Estaño/síntesis química , Espectrofotometría Infrarroja , Células Tumorales CultivadasRESUMEN
Formation constants for thallium(I) complexes of L-cysteine (CysH2), DL-penicillamine (PenH2), N-acetyl-L-cysteine (AcyH2), and N-acetyl-DL-penicillamine (ApeH2) in aqueous solution have been determined in 150 mmol dm-3 NaCl medium at 37 degrees C by potentiometric titrations using a glass electrode. Glycine has been used as a model for simple amino acids. The experimental data may be explained by the formation of the complexes T1(Cys)-, T1(Cys)H, T1(Pen)-, T1(Pen)H, T1(Acy)-, and T1(Ape)- with log formation constants 3.26, 11.28, 3.60, 12.05, 2.27, and 2.45, respectively. Analysis of the results obtained and comparison of thallium(I) complexing ability with that of dimethyl-thallium(III) seem to indicate that thallium(I) toxicity does not directly stem from its interference with the metabolism of sulphur-containing compounds.
Asunto(s)
Aminoácidos , Talio , Acetilcisteína , Aminoácidos/metabolismo , Fenómenos Químicos , Química , Cisteína , Cinética , Penicilamina/análogos & derivados , Potenciometría , Talio/metabolismoRESUMEN
The complexes M(DHDC)2, CH3Hg(DHDC), and C6H5Hg(DHDC) (M = Zn, Cd, Hg; DHDC = N,N-di(2-hydroxyethyl)dithiocarbamate) were prepared and investigated in solution and in the solid state by using 1H and 13C NMR, ir, and Raman spectroscopy. The dithiocarbamate group is anisobidentate and the complexes are associated in solution and the solid state via hydrogen bonding. The possible relation of these structural properties to the behavior of DHDC in the treatment of cadmium poisoning is discussed.