Cobalt-containing Compounds Research Articles

STUDY OF THE INFLUENCE OF (Mg, Co) BIS(CITRATO)GERMANATES ON MORPHOLOGICAL CHANGES OF THE LIVER

The search for new and safe drugs has led to a purposeful synthesis of coordination compounds of metals with bioligands based on metals - hermacite (magnesium bis (citrate) germanate), gercocyte (magnesium bis (citrate) germanate). The aim of the study was to investigate the morphological changes in the liver of rats after administration of (Mg, Co) bis (citrate) germanates in subacute and subchronic experiment. Materials and methods of research. The experiment was performed on mature male Wistar rats weighing 180-250 g, which for 28 days and 3 months intraperitoneally administered (Mg, Co) bis (citrate) germanates at doses of 1/40, 1/110 and 1/135 LD50 and studied morphological changes in the liver. Research results and their discussion. The course of administration of compounds at doses of 1/40 LD50 for 28 days was accompanied by dyscirculatory changes in the liver, as well as moderately pronounced dystrophic changes in hepatocytes. In general, more pronounced changes in the tissues of rats were observed under the influence of hercocytes (foci of destruction of liver tissue). The course of administration of doses of 1/40 LD50 for 3 months was marked by more pronounced dystrophic changes in the liver. Subchronic course administration of compounds at doses of 1/110 LD50 was accompanied by minor morphological changes. When comparing morphological changes in rat tissues, cobalt-containing compound had a slightly more pronounced effect. It is noteworthy that toxic effects did not accompany the course of administration of BAS with doses of 1/135 LD50 and liver tissue did not differ from the control group. Key words: (Mg, Co) bis (citrate) germanates, subacute toxicity, morphological changes.

Molecular modification of planar four-coordinated cobalt active site for the electrochemical reduction of carbon dioxide: a density functional theory study

A systematic theoretical investigation on the carbon dioxide reduction reaction over ten single cobalt-containing compounds was performed to screen the excellent catalyst candidates from the thermodynamics perspective.

A Cobalt-Containing Compound as a Stronger Inhibitor than Galantamine to Inhibit Acetylcholinesterase Activity: A New Drug Candidate for Alzheimer's Disease Treatment.

Acetylcholinesterase (AChE) regulates the transmission of neural messages by hydrolyzing acetylcholine in synaptic spaces. The effects of many AChE inhibitors have been evaluated in the treatment of Alzheimer's disease, but the present study examined a synthetic complex containing cobalt (SC) for the first time in the field of enzyme activity to evaluate enzyme inhibitory function. Ellman's test was applied. AChE function was assessed in the presence of SC through docking and molecular dynamics analyses. The second structure of AChE was studied through circular dichroism (CD) spectroscopy. Several enzymatic methods were utilized for the kinetics of AChE, which indicated the non-Michaelis and positive homotropic behavior of AChE in the absence of inhibitors (Hill coefficient = 1.33). However, the existence of inhibitors did not eliminate this homotropic state, and even AChE had a more sigmoidal shape than the galantamine at the presence of SC. Based on the CD spectroscopy results, AChE structure changed in the existence of inhibitors and substrates. Bioinformatics analysis revealed SC bonding to the channel of active site AChE. The number of hydrogen bonds was such that the flexibility of the enzyme protein structure due to inhibitor binding reduced AChE function. The results reflected that AChE exhibited a non-Michaelis and positive homotropic behavior, leading to a more inhibitory effect on the SC than the galantamine. The positive homotropic behavior of AChE was intensified due to the alteration in AChE protein structure by binding SC to hydrophobic region in the active site pathway and impressing Trp84.

The effect of (Mg, Co) bis (citrate) germanates on morphological changes in brain tissue

Introduction. The problem of safety of pharmacotherapy is becoming more and more urgent all over the world. This is primarily due to the increase in the number of medicines and their widespread use. The use of pharmacotherapeutic agents is usually accompanied by the occurrence of adverse reactions, which differ in their manifestations and degree of severity. Safe use of medicines is one of the priority tasks of modern health care. Therefore, when studying new biologically active substances – future medicines, special attention is paid to information about their toxicity. The search for new effective and safe medicines is a rather complex and long process. One of the well-known ways of searching is based on the detection of biologically active substances (BAS) involved in life processes, pathophysiological and pathochemical processes that underlie the pathogenesis of various diseases. Guided by these principles under the leadership of Professor Seyfullina I.Y. at the Department of Inorganic Chemistry and Chemical Education of Odesa National University named after I.I. Mechnikov, a number of biologically active substances were synthesized – coordination compounds based on germanium, vitamins, microelements, and organic acids acted as bioligands. Purposefully synthesized: magnesium bis(citrato)germanate – hermacite, cobalt bis(citrato)germanate – hercocite. The acute toxicity of BAR was studied: magnesium bis (citrato) germanate LD50= (3049.55±42.54) mg/kg of rat weight, cobalt bis (citrato) germanate LD50= (185.00±4.23) mg/kg. The aim of the work was to study the morphological changes in the brain tissue of rats after administration of (Mg, Co) bis (citrate) germanates in subacute and subchronic experiments. Research methodology and methods. An experimental study was conducted on sexually mature male Wistar rats weighing 180-250 g, which were injected intraperitoneally with (Mg, Co) bis (citrate) germanates in doses of 1/40, 1/110 and 1 /135 LD50. At the same time, it was previously proven that the main pharmacological properties of the compound were manifested by doses of 1/110 and 1/135 LD50. After decapitation, macro- and microscopic examination of the brain tissue was carried out. When conducting the experiment, the general principles of the European Convention for the Protection of Vertebrate Animals, Directive 2010/63/EU of the European Parliament and the Council of the European Union dated September 21, 2010 on the protection of animals used for scientific purposes were observed. Research results and their discussion. The introduction of coordination compounds of metals for 28 days at a dose of 1/40 LD50 caused the appearance of perivascular and pericellular edema in the tissue of the brain, which was more pronounced for the cobalt-containing compound. Administration of hermacyt in doses of 1/40 LD50 for 3 months led to the appearance of areas of necrotized brain tissue, and administration of hercocyte led to the appearance of areas of destruction of brain tissue with the formation of small cavities. Administration of BAR in doses of 1/110 LD50 for 28 days and 3 months was accompanied by minor morphological changes (moderately expressed perivascular and pericellular edema). When BAR was used in doses of 1/135 LD50, the tissue of the brain of rats had minor changes (fullness of individual vessels of the microcirculatory channel, around which there is moderate edema). Conclusions. Thus, new multimetallic coordination compounds (Mg, Co) bis(citrate) germanate in effective doses in subacute and subchronic experiments did not show toxic effects on brain tissues and are promising for further study and establishment of pharmacological properties.

Enhanced sensitivity and detection range of FRET-based vitamin B12 nanosensor.

Vitamin B12 (cobalamin) is a cobalt-containing compound that acts as an essential co-factor for various enzymes involved in the metabolic processes of the living cells. The constructed FRET Sensor for Vitamin Anemia Linked (SenVitAL) displayed marginal FRET efficiency. Here, we report the development of a molecular SenVitAL containing enhanced cyan fluorescent protein (ECFP) and venus as FRET pair to improve the FRET efficiency for optical imaging and screening of already developed sensor by our group. The sensor is the improved version of previously reported SenVitAL and consists of ECFP/venus as FRET pair instead of the originally used pair CFP/YFP. To increase the physiological range of vitamin B12 measurement, affinity mutants were created. Compared to the wild type, SenVitAL-5 with W44Q mutation has higher affinity and displayed large dynamic detection range (0.10-480µM) in response to vitamin B12 binding. For cell-based monitoring and dynamic measurement of vitamin B12 flux rates, SenVitAL-5 was successfully expressed in cytosol of yeast and mammalian cells. Changes in the emission intensities of the two fluorophores were detected using confocal microscopy in both cell types in response to vitamin B12. With the addition of 50µM extracellular vitamin B12 to the cells, the emission intensity of venus increased and that of ECFP decreased over the time. Furthermore, the results show that the variant SenVitAL-5 measures the vitamin B12 in a concentration-dependent manner, showing the resulting increase in the FRET ratio and thus confirming its utility as an ideal fluorescent indicator for the detection of vitamin B12 in eukaryotic systems in real time.

Organometallic MFU-4l(arge) Metal–Organic Frameworks

Ligand exchange reactions at the Kuratowski-type secondary building unit in MFU-4l(arge) metal–organic frameworks (MOFs) result in organometallic porous compounds with metal–carbon bonds of the general formula [Zn5LxCl4–x(BTDD)3] (4 ≥ x > 3; L = methanido, ethanido, n-butanido, tert-butanido, 3,3-dimethyl-1-butyn-1-ido; H2-BTDD = bis(1H-1,2,3-triazolo[4,5-b][4′,5′-i])dibenzo[1,4]dioxin) and [Zn1.5Co3.5Me3.1Cl0.9(BTDD)3]. The compounds were characterized by FT-IR, EDX spectroscopy, X-ray powder diffraction (XRPD), and argon adsorption measurements. VT-XRPD, TGA, and TG-MS measurements were applied to investigate the thermal and oxidative stability of the organometallic Zn-MFU-4l derivatives. The hydrolytic stability of all compounds was examined, and a conversion of the methanide to hydroxide ligands is observed in the cobalt-containing compound. DRIFTS measurements of the resulting framework with the composition [Zn1.4Co3.6(OH)3.1Cl0.9(BTDD)3] revealed a mechanism of carbon dioxide binding similar to that...

Black Sea fish and shellfish as essential source of vitamin B12

<p class="abstract"><strong>Background:</strong> Vitamins are very important for the human body because they are necessary for many biological absorption processes of other nutrients, for cells and tissues growth and repair. Because of this, there are many recommendations on daily vitamins intake, approved by the different country and world food organizations. Usually under the term "vitamin B<sub>12</sub>" is understood only cyanocobalamin, but actually this name is general and covers all potentially biologically active "cobalamins"- a group of cobalt-containing compounds. Animal foods, as different meat, milk, eggs, fish and shellfish are considered as the main dietary sources of this vitamin. They contain different forms (methylcobalamin and deoxyadenosylcobalamin) of vitamin B<sub>12</sub> in different amounts. There is limited information in the scientific literature about the vitamin B<sub>12</sub> content in black sea fish and shellfish. The aims of the present work were to determine and compare vitamin B<sub>12</sub> contents as well as relative daily intake of vitamins in different fish and shellfish species from Black Sea waters.</p><p class="abstract"><strong>Methods:</strong> Vitamin B<sub>12</sub> was analysed spectrophotometrically. The method for quantitative analysis includes extraction from the edible tissue and enzymatic hydrolysis to release the cobalt ions. </p><p class="abstract"><strong>Results:</strong> The quantities of vitamin B<sub>12</sub> found in the edible tissue of the analysed samples ranged from 0.63 μg.100 g<sup>-1</sup> ww to 21.5 μg.100 g<sup>-1</sup> ww.</p><p class="abstract"><strong>Conclusions:</strong> The observed results confirm that all fish and molluscs samples deliver significant quantities of the water-soluble vitamin B<sub>12</sub>.</p><p> </p>

Determination of cobalt species in nutritional supplements using ICP-OES after microwave-assisted extraction and solid-phase extraction

Cobalt content (as vitamin B12 and inorganic cobalt) in two nutritional supplements, namely Spirulina platensis and Saccharomyces cerevisiae known as a “superfood”, has been determined using inductively coupled plasma optical emission spectrometry (ICP-OES). Several sample pre-treatment protocols have been applied and compared. Microwave-assisted acid digestion efficiently decomposed all cobalt-containing compounds, thus allowed obtaining total cobalt content in supplements examined. Vitamin B12 was extracted from the samples with acetate buffer and potassium cyanide solution exposed to mild microwave radiation for 30 min, and cyanocobalamin was separated from the extract by on-column solid phase extraction using C-18 modified silica bed. About 100% of cobalt species was extracted using the triple microwave-assisted extraction procedure. Total cobalt content was 20-fold greater in Spirulina tablets than the declared cobalamin content (as Co). The ICP-OES method precision was about 3% and detection limit was 1.9 and 2.7 ng Co mL−1 for inorganic cobalt or cyanocobalamin, respectively.

The Potent Inhibitory Effect of a Naproxen-Appended Cobalt(III)-Cyclam Complex on Cancer Stem Cells.

We report the potency against cancer stem cells (CSCs) of a new cobalt(III)-cyclam complex (1) that bears the nonsteroidal anti-inflammatory drug, naproxen. The complex displays selective potency for breast CSC-enriched HMLER-shEcad cells over breast CSC-depleted HMLER cells. Additionally, it inhibited the formation of three-dimensional tumour-like mammospheres, and reduced their viability to a greater extent than clinically used breast cancer drugs (vinorelbine, cisplatin and paclitaxel). The anti-mammosphere potency of 1 was enhanced under hypoxia-mimicking conditions. Detailed mechanistic studies revealed that DNA damage and cyclooxygenase-2 (COX-2) inhibition contribute to the cytotoxic mechanism of 1. To the best of our knowledge, 1 is the first cobalt-containing compound to show selective potency for CSCs over bulk cancer cells.

Advances in cobalt complexes as anticancer agents.

The evolution of resistance to traditional platinum-based anticancer drugs has compelled researchers to investigate the cytostatic properties of alternative transition metal-based compounds. The anticancer potential of cobalt complexes has been extensively studied over the last three decades, and much time has been devoted to understanding their mechanisms of action. This perspective catalogues the development of antiproliferative cobalt complexes, and provides an in depth analysis of their mode of action. Early studies on simple cobalt coordination complexes, Schiff base complexes, and cobalt-carbonyl clusters will be documented. The physiologically relevant redox properties of cobalt will be highlighted and the role this plays in the preparation of hypoxia selective prodrugs and imaging agents will be discussed. The use of cobalt-containing cobalamin as a cancer specific delivery agent for cytotoxins will also be described. The work summarised in this perspective shows that the biochemical and biophysical properties of cobalt-containing compounds can be fine-tuned to produce new generations of anticancer agents with clinically relevant efficacies.

Vitamin B12 absorption: Mammalian physiology and acquired and inherited disorders

Vitamin B12 (cobalamin) is a cobalt-containing compound synthesized by bacteria and an essential nutrient in mammals, which take it up from diet. The absorption and distribution of dietary vitamin B12 to the organism is a complex process involving several gene products including carrier proteins, plasma membrane receptors and transporters. Disturbed cellular entry, transit or egress of vitamin B12 may lead to low vitamin B12 status or deficiency and eventually hematological and neurological disorders. The aim of this review is to summarize the causes leading to vitamin B12 deficiency including decreased intake, impaired absorption and increased requirements. Under physiological conditions, vitamin B12 bound to the gastric intrinsic factor is internalized in the ileum by a highly specific receptor complex composed by Cubilin (Cubn) and Amnionless (Amn). Following exit of vitamin B12 from the ileum, general cellular uptake from the circulation requires the transcobalamin receptor CD320 whereas kidney reabsorption of cobalamin depends on Megalin (Lrp2). Whereas malabsorption of vitamin B12 is most commonly seen in the elderly, selective pediatric, nondietary-induced B12 deficiency is generally due to inherited disorders including the Imerslund-Gräsbeck syndrome and the much rarer intrinsic factor deficiency. Biochemical, clinical and genetic research on these disorders considerably improved our knowledge of vitamin B12 absorption. This review describes basic and recent findings on the intestinal handling of vitamin B12 and its importance in health and disease.

Effect of Cobalt Incorporation and Lithium Enrichment in Lithium Nickel Manganese Oxides

Candidate cathode materials of cobalt-incorporated and lithium-enriched have been prepared by a coprecipitation method and a solid-state reaction. We systematically investigated the effect of both cobalt presence and lithium concentration on the structure, physical properties, and electrochemical behavior of the studied samples. The electrochemical performance of the cobalt-containing compounds showed much less dependence on the variation in the lithium amounts compared to the cobalt-free counterpart. The study demonstrated that even with cobalt incorporation, proper lithium content is the key to desirable cathode materials with nanostructured primary particles that are indispensable to achieve high capacity and high rate capability and, therefore, both improved energy and power densities for lithium-ion batteries.

Determination of Cobalamin in Nutritive Supplements and Chlorella Foods by Capillary Electrophoresis−Inductively Coupled Plasma Mass Spectrometry

A capillary electrophoresis-inductively coupled plasma mass spectrometric (CE-ICP-MS) method for the determination of cobalamin is described. Samples of cobalt-containing compounds were subjected to electrophoretic separation before injection into the microconcentric nebulizer (CEI-100) of ICP-MS. The Co-containing compounds studied include cyanocobalamin (CN-Cbl, vitamin B12), hydroxocobalamin (OH-Cbl), and Co(II). The species studied were well separated using a 70 cm lengthx75 microm i.d. fused silica capillary with the applied voltage set at +20 kV. A 25 mM Tris buffer (pH 9.0) containing 15 mM sodium dodecyl sulfate (SDS) was used as the electrophoretic buffer. The CE-ICP-MS detection limits were 0.3, 0.2, and 1.7 ng of Co mL(-1) for CN-Cbl, OH-Cbl, and Co(II), respectively. The concentrations of cobalamin compounds were determined in selected nutritive supplements and chlorella samples. A microwave-assisted extraction method was used for the extraction of these compounds. Over 92% of the total cobalt species was extracted using a 5% v/v HNO3 solution in a focused microwave field within a period of 10 min; spike recovery was in the range of 94-105% for various species. The major cobalt species in nutritive supplements and chlorella samples was cyanocobalamin.

Third-order nonlinear optical susceptibilities of the Langmuir–Blodgett films of octa-substituted metallophthalocyanines

The third-order susceptibilities χ(3)(−3ω:ω,ω,ω) of Langmuir–Blodgett films of a series of octasubstituted metallophthalocyanines have been measured by third-harmonic generation experiments at 1.064 and 1.904 μm. For the latter excitation wavelength a marked enhancement of the nonlinearity for the cobalt-containing compound has been found, and χ(3) values are one order of magnitude larger than for the other systems. The effect has been associated to the role of two-photon allowed metal (possibly d−d) transitions in the cobalt derivative.

Effect of surface area on CO oxidation by the perovskite catalysts La1?x Sr x MO3-? (M = Co, Cr)

The catalytic oxidation of carbon monoxide by two compounds in the system La0.8 Sr0.2MO3-δ (M = Co, Cr) was measured at different BET surface areas of the oxide materials. The light-off temperature was found to decrease with increasing surface area up to a certain level beyond which it remained constant for the cobalt-containing compound. This limiting value could not be attained for the chromium-containing compound because of equilibration problems in the preparation. As the active catalytic area as distinct from the total (BET) catalyst area was not clarified, these preliminary results show the need for further inquiry.

ChemInform Abstract: Thermal Decomposition of Potassium Cobalt Hexacyanoferrate(II)

Abstract Potassium cobalt hexacyanoferrate(II), K2CoFe(CN)6 · 1.4H2O, loses its water when heated up to 170°C, and the anhydrous compound begins to decompose above 230°C. The cyanide groups are evaporated off in the temperature range 230–350°C, and the solid products thus formed are K2CO3, Fe2O3, Co3O4 and CoFe2O4. In the range 550–900°C, the cobalt-containing compounds become CoO, and K2CO3 probably partly decomposes to K2O, so that the product mixture at 900°C is K2CO3/K2O, Fe2O3 and CoO. Above this temperature, K2CO3 decomposes to K2O.

Thermal decomposition of potassium cobalt hexacyanoferrate(II)

Potassium cobalt hexacyanoferrate(II), K 2CoFe(CN) 6 · 1.4H 2O, loses its water when heated up to 170°C, and the anhydrous compound begins to decompose above 230°C. The cyanide groups are evaporated off in the temperature range 230–350°C, and the solid products thus formed are K 2CO 3, Fe 2O 3, Co 3O 4 and CoFe 2O 4. In the range 550–900°C, the cobalt-containing compounds become CoO, and K 2CO 3 probably partly decomposes to K 2O, so that the product mixture at 900°C is K 2CO 3/K 2O, Fe 2O 3 and CoO. Above this temperature, K 2CO 3 decomposes to K 2O.

Coenzyme function of cobalamin analogues from calf kidney

Calf kidney has been used as a tissue source for the isolation of cobalamin analogues, which are defined here as cobalt-containing compounds of distinctive chromatographic behavior that are extractable from tissues by methods conventionally used to extract cobalamin and which, in radioisotope dilution assays, are more active with R-protein as binder than intrinsic factor and are relatively less active in microbiologic assays. Preparatory methods employed reverse affinity chromatography or a series of chemical extractions for the isolation of corrin followed by Dowex-50 chromatography. An analogue-containing fraction (peak 2) was eluted by acetate buffers between pH 4 and 5. This material was shown to contain cobalt, to migrate differently than the four cobalamins in Dowex-50 and paper chromatography, and to display a pattern of properties that is compatible with the above definition of cobalamin analogues. These analogues stimulated crude preparations of N5-methyltetrahydrofolate-homocysteine methyltransferase (EC 2.1.1.13) from Escherichia coli and rat liver at far lower concentrations (1-40 nmol/L) than the major cobalamins. No evidence of enzymatic conversion of cobalamin to analogue could be demonstrated.

Coenzyme Function of Cobalamin Analogues From Calf Kidney

Abstract Calf kidney has been used as a tissue source for the isolation of cobalamin analogues, which are defined here as cobalt-containing compounds of distinctive chromatographic behavior that are extractable from tissues by methods conventionally used to extract cobalamin and which, in radioisotope dilution assays, are more active with R-protein as binder than intrinsic factor and are relatively less active in microbiologic assays. Preparatory methods employed reverse affinity chromatography or a series of chemical extractions for the isolation of corrin followed by Dowex-50 chromatography. An analogue-containing fraction (peak 2) was eluted by acetate buffers between pH 4 and 5. This material was shown to contain cobalt, to migrate differently than the four cobalamins in Dowex-50 and paper chromatography, and to display a pattern of properties that is compatible with the above definition of cobalamin analogues. These analogues stimulated crude preparations of N5-methyltetrahydrofolate-homocysteine methyltransferase (EC 2.1.1.13) from Escherichia coli and rat liver at far lower concentrations (1–40 nmol/L) than the major cobalamins. No evidence of enzymatic conversion of cobalamin to analogue could be demonstrated.

A pharmacologic evaluation of certain cobalt-containing hemopoietic agents

Gastrointestinal absorption of cobalt-containing compounds appears to depend, in part, on a mechanism which concerns cobalt alone and is not dependent on the remainder of the molecule. The systemic toxicity appears to increase directly with the dissociation to supply cobalt ion. Cobalt disodium ethylenediamine tetra-acetate shows little dissociation and little systemic toxicity. The enhancement of erythropoietin formation can be accomplished in approximately the same degree by equivalent cobalt doses given as ionic cobalt, complex-ion, or difficultly dissociated chelated cobalt. This is subsequently reflected in peripheral blood indexes. Both cobalt polyglucopyranose and cobalt disodium ethylenediamine tetra-acetate have higher therapeutic indexes, as determined in the rat, than does cobalt chloride. Both would appear suitable for clinical trial. No evidence of chronic toxicity was found from prolonged oral administration of cobalt polyglucopyranose or cobalt disodium ethylenediamine tetra-acetate in the rat. Cobalt disodium ethylenediamine tetra-acetate (Copoietin A) appears to represent the most satisfactory type of cobalt compound tested and should be worthy of clinical trial as a therapeutic agent.