ABSTRACT
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.
Subject(s)
Acrylates/chemistry , Cadmium/toxicity , Coordination Complexes/chemistry , Protective Agents/chemistry , Zinc/chemistry , Animals , Cell Line , Coordination Complexes/chemical synthesis , Crystallography, X-Ray , Hep G2 Cells , Humans , Magnetic Resonance Spectroscopy , Molecular Conformation , Protective Agents/chemical synthesis , SwineABSTRACT
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.
Subject(s)
Organotin Compounds/chemistry , Organotin Compounds/pharmacology , Cell Differentiation/drug effects , Cell Division/drug effects , Crystallography, X-Ray , Humans , K562 Cells , Ligands , Magnetic Resonance Spectroscopy , Molecular Structure , Organotin Compounds/chemical synthesis , Spectrophotometry, InfraredABSTRACT
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.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Organotin Compounds/chemical synthesis , Organotin Compounds/pharmacology , Pyridoxal/analogs & derivatives , Thiosemicarbazones/chemical synthesis , Thiosemicarbazones/pharmacology , Animals , Antineoplastic Agents/chemistry , Cell Differentiation/drug effects , Cell Division/drug effects , DNA, Neoplasm/biosynthesis , Dimethyl Sulfoxide/pharmacology , Friend murine leukemia virus , Leukemia, Erythroblastic, Acute/drug therapy , Leukemia, Erythroblastic, Acute/metabolism , Leukemia, Erythroblastic, Acute/pathology , Magnetic Resonance Spectroscopy , Mass Spectrometry , Mice , Organotin Compounds/chemistry , Pyridoxal/chemical synthesis , Pyridoxal/chemistry , Pyridoxal/pharmacology , Reverse Transcriptase Inhibitors/chemical synthesis , Reverse Transcriptase Inhibitors/chemistry , Reverse Transcriptase Inhibitors/pharmacology , Spectroscopy, Mossbauer , Thiosemicarbazones/chemistry , Tumor Cells, CulturedABSTRACT
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.
Subject(s)
Antineoplastic Agents/chemical synthesis , Organotin Compounds/chemical synthesis , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Differentiation/drug effects , Cell Division/drug effects , Crystallography, X-Ray , Friend murine leukemia virus , Leukemia, Erythroblastic, Acute/drug therapy , Mice , Models, Molecular , Molecular Structure , Organotin Compounds/chemistry , Organotin Compounds/pharmacology , Solutions , Spectrophotometry, Infrared , Tumor Cells, CulturedABSTRACT
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.
Subject(s)
Cadmium/metabolism , Pyridoxine/metabolism , Animals , Cadmium/administration & dosage , Cadmium/chemistry , Cadmium/toxicity , Cadmium Chloride , Chlorides/administration & dosage , Chlorides/toxicity , Drug Interactions , Kidney/drug effects , Kidney/metabolism , Liver/drug effects , Liver/metabolism , Magnetic Resonance Spectroscopy , Male , Pyridoxine/chemistry , Pyridoxine/pharmacology , Rats , Rats, Inbred Strains , Solubility , Spectrophotometry, InfraredABSTRACT
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.
Subject(s)
Cadmium/toxicity , Vitamin B 12/pharmacology , Animals , Cadmium/pharmacokinetics , Cadmium Chloride , Kidney/drug effects , Kidney/metabolism , Lethal Dose 50 , Liver/drug effects , Liver/metabolism , Magnetic Resonance Spectroscopy/methods , Male , Rats , Rats, Inbred Strains , Tissue DistributionABSTRACT
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.
Subject(s)
Antineoplastic Agents , Cell Division/drug effects , Halogens/pharmacology , Imidazoles/pharmacology , Leukemia P388/drug therapy , Leukemia, Experimental/drug therapy , Organotin Compounds/pharmacology , Animals , Chemical Phenomena , Chemistry , Halogens/chemical synthesis , Imidazoles/chemical synthesis , Magnetic Resonance Spectroscopy , Mice , Mice, Inbred DBA , Organotin Compounds/chemical synthesis , Spectrophotometry, Infrared , Tumor Cells, CulturedABSTRACT
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.
Subject(s)
Amino Acids , Thallium , Acetylcysteine , Amino Acids/metabolism , Chemical Phenomena , Chemistry , Cysteine , Kinetics , Penicillamine/analogs & derivatives , Potentiometry , Thallium/metabolismABSTRACT
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.
