Synthesis of poly-Schiff bases and some copper(II) and manganese(lI) polychelates

Four poly-Schiff bases derived from hydroxyketones and aromatic diamines have been synthesized, and their copper and manganese complexes were prepared and charactefized by elemental analyses, spectral, magnetic and thermal data. The polychelates are of 1:1 (metal-poly-Schiff base) stoichiometry and exhibit four and six-coordination for copper and manganese respectively. The chelation is through the nitrogen of the azomethine group and oxygen of hydroxy group in the poly-Schiff bases.     

Synthesis, structure and properties of copper(II) and manganese(II) coordination polymers with 1,5-dinitronaphthalene-3,7-dicarboxylate

Two new metal-organic coordination polymers with 1,5-dinitronaphthalene-3,7-dicarboxylate (NNDC), [Cu₂(NNDC)₂(DMF)_1.8(DMSO)_2.2(H₂O)₂]·H₂O (1) and [Mn₃(NNDC)₃(DMSO)₄]·2DMSO (2) have been synthesized under solvothermal conditions and characterized by single crystal X-ray diffraction and Thermogravimetric Analysis (TGA). The structure of compound 1 consists of one-dimensional chains with copper ions being linked by the dicarboxylate ligands. The coordination chains are associated into ladder-like double chains through O-H?O hydrogen bonds and π-π interactions, and the ladders are packed in a cross fashion through further π-π interactions to give the three-dimensional structure. The Mn(II) compound exhibits a 3D framework with the pcu topology, in which [Mn₃(COO)₆] clusters as octahedral secondary building blocks are linked by the naphthalene spacers. Magnetic analyses were carried out based on both temperature- and field-dependent data, consistently suggesting relatively weak antiferromagnetic interactions within the carboxylate bridged [Mn₃(COO)₆] cluster.     

Suppression and regeneration of rat bone marrow under the influence of methotrexate. An EM study.

Adult male rats were given daily injections of methotrexate for 12 days, during which time specimens of femoral bone marrow were taken for correlative light- and electron-microscopic study. After 12 days methotrexate was discontinued and specimens were taken the marrow recovered from the effect of methotrexate. Normal rat bone marrow was used as a basis of comparison. As methotrexate was administered, cell division ceased and the immature erythroblasts and myelocytes proceeded in the maturational process and a rapid hypocellularity of the marrow developed. Eosinophilic leukocytes, lymphocytes, large fat cells, erythrocytes, and phagocytic reticuloendothelial cells were the only formed elements remaining after 12 days of methotrexate treatment. Two days after methotrexate was discontinued, myeloblasts, myelocytes and proerythroblasts were plentiful, and on the third day the marrow exhibited an erythroid hyperplasia. By the eighth day all cell types were present though the marrow still was hypocellular. 14 days post methotrexate the marrow returned to normal.     

Determination of the interaction of ADP and dADP with copper(II), manganese(II) and lanthanide(III) ions by nuclear-magnetic-resonance spectroscopy.

The aqueous solution conformation of the 1:1 complexes of ADP and dADP bound to a lanthanide ion have been determined by examination of the dipolar shifts and induced relaxation at pH 6.4. Apparent inconsistencies in the observed data are interpreted in terms of a gradually changing lanthanide-oxygen bond length from Pr3+ to Yb3+. The conformations of ADP and dADP are very similar showing an extended diphosphate, a 2E ribose conformation and with the adenine base displaying a small syn contribution. Relaxation data obtained from Mn(II) titrations are readily interpreted in terms of bidentate coordination to alpha and beta phosphates with the nucleotides retaining the same overall conformation found from the lanthanide study. No evidence to support an intramolecular water-bridged backbound structure is observed. The interaction with Cu(II) is more complex, coordination is observed not only at the diphosphate but also at two sites on the base, N-1, and the chelate formed between N-7 and the amino group. The relative importance of these sites is different for ADP and dADP and is also pH-dependent for ADP.     

Synthesis, characterization and antifungal activity of a series of manganese(II) and copper(II) complexes with ligands derived from reduced N,N'-O-phenylenebis(salicylideneimine)

A series of manganese(II) and copper(II) complexes with reduced Schiff bases derived from o-phenylenediamine has been prepared and characterized by elemental analysis, TG measurements, ESR, magnetic measurements, FTIR, UV-Visible spectra and conductivity. These complexes were found to be [MnL(H2O)n] and [CuL](H2O)n species with n=0-2. Their antifungal activity was evaluated on different human fungi including yeasts of the Candida genus (C. albicans, C. glabrata, C. tropicalis and C. parapsilopsis) some opportunistic moulds belonging to the Aspergillus (A. fumigatus, A. terreus and A. flavus), Scedosporium genus (S. apiospermum and S. prolificans) and some dermatophytes (M. gypseum, M. persicolor, T. mentagrophytes, M. canis and T. tonsurans). The manganese complexes showed a significant growth inhibition of the dermatophytes tested and fungi of the genus Scedosporium. This is very interesting as these fungi are usually poorly susceptible to current antifungal including Amphotericin B and Itraconazole chosen as reference in this study.     

Oncostatic treatment effect of triple negative breast cancer cell line with copper (I)-nicotinate complex

The treatment of triple-negative breast cancer (TNBC) remains a major challenge. The present study aimed to throw more light on the role of copper (I)-nicotinate complex (CNC) as an antitumor as well as a proapoptotic agent. In this study, the HCC-1806 cell line was used as a model for TNBC. Cell cycle, apoptosis assay, and programmed cell death protein-1 were investigated by flowcytometry. Besides, the comet assay was performed using a fluorescence microscope. The enzyme-linked immunosorbent assay technique was used for the detection of phospho-Chk1 at ser 317 and caspase-3. Moreover, the gene expression of survivin was identified by real-time polymerase chain reaction. Finally, superoxide dismutase (SOD) was calorimetrically assayed. The viability of HCC-1806 cells treated with CNC was decreased in a dose-dependent manner. The tendency for apoptotic machinery was observed through the increase in the sub G0 peak, the percentage of early and late apoptotic phases, and the elevation in caspase-3 levels associated with a downregulation of the survivin gene expression. The antioxidant property of the complex, reflected by elevated SOD activity, may contribute to mediate the cell death pathways. Low concentrations of CNC were found to favor the apoptotis-mediated mechanism. However, one cannot neglect the abundance of cell necrosis–mediated death of cells via CNC, especially at higher concentrations.     

Transport and distribution of copper injected into an albumin-deficient (analbuminemic) rat

Copper (Cu) concentrations in blood, liver, kidney, spleen and pancreas of an albumin-deficient (Nagase analbuminemic) rat (NAR) were compared with those of a control (Sprague-Dawley) rat (SDR). Cu concentrations were significantly higher in the blood and significantly lower in the liver of the NAR strain than those of the SDR strain in female control (saline-injected) groups at 8 weeks old. Female NAR and SDR 8-week-old rats were injected i.p. with Cu at a single dose of 2.0 mg/kg body wt and killed 18 hr later. Concentrations of Cu and other essential elements in the blood, liver, kidney, spleen and pancreas were determined simultaneously by inductively coupled plasma-atomic emission spectrometry. Cu concentration in the liver was significantly lower in the NAR than in the SDR strain suggesting a role for albumin as a carrier protein of free Cu ions in the blood. The effects of Cu loading on other essential elements (Zn, Fe, Ca, Mg, P) were also compared between the NAR and SDR strains.     

Changes in the skin epithelium and nerve elements of the rat sole with directed regeneration of the sciatic nerve

The work has been performed on Wistar rats and non-inbred animals. Their ischiatic nerves have been dissected at the femoral superior third under nembutal narcosis. The end of the sectioned nerve are connected by a fragment of an aorta from rats of the same age. The state of nervous elements and dermal epithelium of the hind extremity sole in the animals is studied by means of general histological and neurohistological techniques. Mitotic activity of cells in the plantar epidermis, thickness as a whole and its separate layers are estimated, keratinization coefficient and correlation of thickness of separate sheaths in the whole layer are calculated. Use of the arterial vessels for connecting the end of the cut ischiatic nerve, trophic ulcers, that usually take place after the nerve section, do not develop. At early stages after the operation mitotic activity in the epidermis decreases by 70%, and the layer thickness--by 40%. Restoration of both indices proceeds slowly. As soon as the regenerating nerve fibers reach the distal part of the ischiatic nerve, the state of the epidermis improves: the mitotic activity differs from the normal by 20-30%, and thickness of the epithelium--by 28-30%. Coordination of thickness of separate layers in the epidermis is not nearly disturbed. It remains in the same state up to complete restoration of receptory structures in the rat plantar skin (during 9-9.5 months after the operation).     

Light-reactivation of (Tris-washed) -DPIP-treated chloroplasts : manganese incorporation, chlorophyll fluorescence, action spectrum and oxygen evolution

Incorporation of ⁵⁴Mn into Tris (pH 8.8, 1 hr)-washed chloroplastsand oxygen evolving activity were stimulated by DPIP treatmentand light-reactivation, but inhibited by atebrin, DCCD, gramicidinJ, DCMU and EDTA. Omission of DTT on the light-reactivationresulted in accumulation or deposit of Mn in chloroplasts whichhad no function for the recovery of oxygen-evolving activity.The chlorophyll fluorescence quenched by Tris-washing was restoredby DPIP-treatment and light-reactivation. The chloroplast structure,monitored by its packed volume and optical density at 750 nm,changed reversibly with inhibition and DPIP-treatment. The actionspectrum of light-reactivation suggested that the effectivelight-receptor might be photosystem II. ¹ Present address: Department of Biological Science, TsukubaUniversity, Niihari, Ibaragi 300-31, Japan. (Received January 7, 1976; )     

Alteration of iron (Fe), copper (Cu), zinc (Zn), and manganese (Mn) tissue levels and speciation in rats with desferioxamine-induced iron deficiency

BioMetals - The objective of the present study was to investigate the impact of iron deficiency and iron replenishment on serum iron (Fe), copper (Cu), manganese (Mn), and zinc (Zn) speciation and...     

Spontaneous resolution of binary copper(II) complexes with racemic dipeptides: crystal structures of glycyl-L-alpha-amino-n-butyrato copper(II) monohydrate, glycyl-D-valinato copper(II) hemihydrate, and glycyl-L-valinato copper(II) hemihydrate

Copper(II) complexes with glycyl-DL-alpha-amino-n-butyric acid (H2gly-DL-but), glycyl-DL-valine (H2gly-DL-val), glycyl-DL-norleucine (H2gly-DL-norleu), glycyl-DL-threonine (H2gly-DL-thr), glycyl-DL-serine (H2gly-DL-ser), glycyl-DL-phenylalanine (H2gly-DL-phe), and glycyl-L-valine (H2gly-L-val), have been prepared and characterized by IR, powder diffuse reflection, CD and ORD spectra, and magnetic susceptibility measurements, and by single-crystal X-ray diffraction. The crystal structures of the copper complex with H2gly-DL-but, the copper complex with H2gly-DL-val, and [Cu(gly-L-val)]n.0.5nH2O have been determined by a single-crystal X-ray diffraction method. As for the structure of the copper complex with H2gly-DL-but, the configuration around the asymmetric carbon atom is similar to that of [Cu(gly-L-val)]n.0.5nH2O. Therefore it is concluded that the copper complex with H2gly-DL-but is [Cu(gly-L-but)]n.nH2O. On the contrary, as for the structure of the copper complex with H2gly-DL-val, the configuration around the asymmetric carbon atom is different from that of [Cu(gly-L-val)]n.0.5nH2O. Therefore it is concluded that the copper complex with H2gly-dl-val is [Cu(gly-D-val)]n.0.5nH2O. So during the crystallization of the copper(II) complexes with H2gly-DL-but and H2gly-DL-val, spontaneous resolution has been observed; the four complexes have separated as [Cu(gly-D-but)]n.nH2O, [Cu(gly-L-but)]n.nH2O, [Cu(gly-D-val)]n.0.5nH2O, and [Cu(gly-L-val)]n.0.5nH2O, respectively. [Cu(gly-L-but)]n.nH2O is orthorhombic with the space group P2(1)2(1)2(1). [Cu(gly-D-val)]n.0.5nH2O and [Cu(gly-L-val)]n.0.5nH2O are monoclinic with the space group C2. In these complexes, the copper atom is in a square-pyramidal geometry, ligated by a peptide nitrogen atom, an amino nitrogen atom, a carboxyl oxygen atom, and a carboxyl oxygen atom and a peptide oxygen atom from neighboring molecules. So these complexes consist of a two-dimensional polymer chain bridged by a carboxyl oxygen atom and a peptide oxygen atom from neighboring molecules. The axial oxygen atom is located above the basal plane and the side chain of an amino acid is located below it. These polymer chains consist of only one or the other type of optical isomers; no racemic dipeptides are found. Therefore, spontaneous resolution has been observed in the crystallization of copper(II) complexes with H2gly-DL-but and H2gly-DL-val. The crystal structure of [Cu(gly-D-val)]n.0.5nH2O agrees almost completely with that of [Cu(gly-L-val)]n.0.5nH2O, except for the configuration around the asymmetric carbon atom.     

Biliary excretion of copper,manganese, and horseradish peroxidase in eisai hyperbilirubinemic mutant rats (EHBRs) with defective biliary excretion of glutathione

A mixture of copper (Cu) (0.38 mg/kg), manganese (Mn) (0.038 mg/kg), and horseradish peroxidase (HRP) (5.0 mg/kg) was injected intravenously (iv) into mature Eisai hyperbilirubinemic rats (EHBRs) and Sprague-Dawley rats (SDRs). Bile was collected at 10-min intervals before and after the injection, under anesthesia. The liver, kidneys, and blood were removed 40 min after the injection. The serum-conjugated bilirubin concentration was 0.85 mg/dL in the EHBRs, but was below detection limits in the SDRs. The bile-reduced glutathione (GSH) concentration was much lower in the EHBRs (0.04 mg/mL) than in the SDRs (1.30 mg/mL). However, the hepatic GSH concentration was about 1.6 times higher in EHBRs (2.26 mg/g liver) than in SDRs (1.43 mg/g liver). The low, excretion of biliary GSH was not caused by the activity of GGT in the liver, since there was no significant difference in the activity between the two groups (5.8±3.4 and 4.6±2.4 μmol p-nitroaniline/g protein/30 min in SDR and EHBR groups, respectively). There was a delay of initial biliary excretion of Cu in EHBRs compared to SDRs. The biliary concentration of Mn was slightly lower in EHBRs than in SDRs. Forty min after the injection of metals, however, there was no difference between hepatic concentrations of the two metals in the two groups. Our results suggest that abnormal deposition of the two metals is not observed naturally in EHBRs. Injected HRP was excreted rapidly and notably in the EHBRs compared to SDRs. Furthermore, the biliary concentration of β-N-acetyl-D-glucosaminidase (β-NAG) was significantly higher in EHBRs than in SDRs. Rapid biliary excretion of Cu, but not of Mn, may be related to the hepatobiliary transport of GSH, but the transport and lysosomal function do not originally regulate the biliary excretion of Cu.     

Scale regeneration of tilapia (Oreochromis niloticus) under various ambient and dietary calcium concentrations

• 1.1. Scale regeneration was examined in Oreochromis niloticus under normal, dietary calcium-deficient, and both dietary and ambient water calcium-deficient conditions.
• 2.2. Calcium contents of regenerating scales were dependent on the calcium status of the fish, but areal growth of the scales was independent.
• 3.3. Transient hypocalcemia accompanied with a loss of calcium from original scales was observed in descaled fish in dietary calcium deficiency, and intact and descaled fish in both dietary and ambient water calcium deficiency.
• 4.4. The results suggested that calcium mobilized from internal sources was insufficient and both water and dietary calcium were necessary for normal calcification of the regenerating scales.

     

The influence of sulfhydryl and sulfoxide on gross regeneration in the Hermit Crab (Pagurus longicarpus)

Summary and conclusion Experimental evidence is presented demonstrating that gross regeneration in the foot of the Hermit Crab (Pagurus longicarpus) is stimulated by the sulfhydryl group and retarded by the sulfoxide, a partially oxidized derivative thereof.Prom this it can be concluded that the chemical equilibrium regulative of growth by increase in cell number is a determinant of regeneration rate as it is in all other types of cell multiplication so far studied.     

Effect of lead in water on the absorption of copper, iron, manganese and zinc by sheep (Ovis aries) infected with sheep tapeworm (Moniezia expansa)

The sheep tapeworm (Moniezia expansa) and its host Ovis aries were analyzed by inductively coupled plasma optical emission spectrometry (ICP-OES) for their copper, iron, manganese, zinc and lead levels. Element concentrations in cestode parasites were compared to those in various organs (liver, kidney, and muscle) of sheep. Tapeworms in the small intestine of sheep that were administered 2g of Pb(CH(3)COO)(2) per os daily (7 days) had significantly higher lead concentrations than sheep tissues. Cu levels significantly increased after Pb administration in sheep muscle and sheep tapeworms. Contrarily, Zn content significantly decreased in sheep muscle, but significantly increased in sheep tapeworms. However, Mn content significantly decreased after Pb administration in sheep tapeworms. Furthermore, Fe content significantly decreased after Pb administration in sheep liver and kidneys.