Copper(II), cobalt(II) and nickel(II) complexes of lapachol: synthesis,DNA interaction,and cytotoxicity

Three novel copper(II), cobalt(II), and nickel(II) complexes of lapachol (Lap) containing 110-phenanthroline (phen) ligand, [M(Lap)₂(phen)] (M=Cu(II), 1, Co(II), 2, and Ni(II), 3), have been synthesized and characterized using, elemental analysis and spectroscopic studies. Their interactions with calf thymus DNA (CT DNA) were investigated using viscosity, thermal denaturation, circular dichorism, fluorescence quenching, and electronic absorption spectroscopy. The DNA cleavage abilities of 1–3 have been studied, where cleavage activity of copper complex 1 is more than the complexes 2 and 3. The in vitro cytotoxic potential of the complexes 1–3 against human cervical carcinoma (HeLa), human liver hepatocellular carcinoma (HepG-2), and human colorectal adenocarcinoma (HT-29) cells indicated their promising antitumor activity with quite low IC₅₀ values in the range of .15–2.41 μM, which are lower than those of cisplatin.     

Antibacterial and antifungal metal based triazole Schiff bases

A new series of four biologically active triazole derived Schiff base ligands (L¹–L⁴) and their cobalt(II), nickel(II), copper(II) and zinc(II) complexes (1–16) have been synthesized and characterized. The ligands were prepared by the condensation reaction of 3-amino-5-methylthio-1H-1,2,4-triazole with chloro-, bromo- and nitro-substituted 2-hydroxybenzaldehyde in an equimolar ratio. The antibacterial and antifungal bioactivity data showed the metal(II) complexes to be more potent antibacterial and antifungal than the parent Schiff bases against one or more bacterial and fungal species.     

Characterization of Heavy Metal Resistance of Metal-Reducing Shewanella Isolates From Marine Sediments

This study focuses on heavy metal resistance of marine, benthic Mn(IV)- and Fe(III)-reducing bacteria and their potential to mobilize heavy metals from sedimentary phases, as hydrous ferric oxides (HFO) and Mn(IV)-oxides (δ -MnO ₂ ). One isolate was obtained from enrichments of metal-polluted sediment with δ -MnO ₂ (strain MB4, 99% similarity to S. marisflavi), and two strains were isolated from enrichments on HFO (strain FB18 and FS8, 98 and 97% 16S rRNA gene similarity to Shewanella collwelliana). The 16S rRNA sequences similar to isolates MB4 and FS8 were detected previously in DGGE profiles and clone libraries of the original sediment samples. Toxicity tests under aerobic conditions showed that the latter two ceased growth at 150 μ M Cu, but strain MB4 and reference strain S. oneidensis MR1 were more tolerant to copper; growth with 150 μ M Cu reached 56–58 ± 0.1% of maximal optical density, OD_max, in control cultures. Similar experiments conducted under anaerobic conditions with fumarate indicated no significant change in copper tolerance in strain MB4 (66 ± 3% OD_max at 150 μ M). Biphasic experiments with δ -MnO ₂ -reduction followed by use of fumarate, furthermore indicated that the presence of manganese oxides decreased bio-availability of copper through sorption processes, thereby alleviating the toxicity of copper to strain MB4 to some extent. Scanning electron microscopic images showed the initial amorphous Mn(IV)-oxides and newly formed, highly crystalline, lemon-shaped, particles making up the precipitate that remained after microbial reduction. Concomitant electron dispersive x-ray spectrometry confirmed presence of copper in the initial sample, yet detected no copper in the precipitate after microbial reduction, indicating that the Mn(IV)-reducing Shewanella strain MB4 mobilized copper adsorbed to δ -MnO ₂ .     

Density functional studies on copper-catalysed asymmetric aziridination of diazoacetate with imines

Density functional theory has been used to study copper(I)-catalysed aziridination of diazoacetate with imines. All the intermediates and the transition states were optimised completely at B3LYP/6-31G(d) level. Calculation results confirm that copper(I)-catalysed aziridination of diazoacetate with imines is exothermic, and the total released Gibbs free energy is about ? 170 kJ/mol. Copper(I)-catalysed aziridination has two reaction modes: I and II, and thus the reaction mode I is dominant. The formation of the copper(I)–carbene–imine complex M3 (i.e. the attack of imines on copper–carbon(carbene) of copper–carbene intermediate M2) is the rate-determining step and the chirality-limiting step for copper-catalysed asymmetric aziridination. The reaction channel CA2 → M1a → TS1a → M2 → TS2a2 → M3a2 → TS3a2 → M4a2 → P1 is the most favourable one. The dominant products predicted theoretically are of (R)-chirality.     

Copper,ceruloplasmin, and long-term cardiovascular and total mortality (The Ludwigshafen Risk and Cardiovascular Health Study)

Abstract

Background. Copper and its main transport protein ceruloplasmin have been suggested to promote the development of atherosclerosis. Most of the data come from experimental and animal model studies. Copper and mortality have not been simultaneously evaluated in patients undergoing coronary angiography. Methods and results. We examined whether serum copper and ceruloplasmin concentrations are associated with angiographic coronary artery disease (CAD) and mortality from all causes and cardiovascular causes in 3253 participants of the Ludwigshafen Risk and Cardiovascular Health Study. Age and sex-adjusted hazard ratios (HR) for death from any cause were 2.23 (95% CI, 1.85–2.68) for copper and 2.63 (95% CI, 2.17–3.20) for ceruloplasmin when we compared the highest with the lowest quartiles. Corresponding hazard ratios (HR) for death from cardiovascular causes were 2.58 (95% CI, 2.05–3.25) and 3.02 (95% CI, 2.36–3.86), respectively. Further adjustments for various risk factors and clinical variables considerably attenuated these associations, which, however, were still statistically significant and the results remained consistent across subgroups. Conclusions. The elevated concentrations of both copper and ceruloplasmin are independently associated with increased risk of mortality from all causes and from cardiovascular causes.     

Structure–activity relationship study of copper(II) complexes with 2-oxo-1,2-dihydroquinoline-3-carbaldehyde (4′-methylbenzoyl) hydrazone: synthesis, structures, DNA and protein interaction studies, antioxidative and cytotoxic activity

Novel 2-oxo-1,2-dihydroquinoline-3-carbaldehyde (4′-methylbenzoyl) hydrazone (H₂L) (1) and its two copper(II) complexes have been synthesized. Single-crystal X-ray diffraction studies revealed that the structure of the new copper(II) chloride complex, [Cu(H₂L)Cl₂]·2H₂O (2), is square pyramidal and that of the copper(II) nitrate complex, [Cu(HL)NO₃]·DMF (3), is square planar. In 2, the copper atom is coordinated by the ligand with ONO donor atoms, one chloride ion in the apical position, and the other chloride in the basal plane. In 3, the ligand coordinates as a uninegative tridentate ONO⁻ species and with one nitrate ion in the basal plane. DNA binding experiments indicated that the ligand and copper(II) complexes can interact with DNA through intercalation. Bovine serum albumin binding studies revealed that the compounds strongly quench the intrinsic fluorescence of bovine serum albumin through a static quenching process. Antioxidative activity tests showed that 1 and its copper(II) complexes have significant radical scavenging activity against free radicals. Cytotoxic activities of the ligand and copper(II) complexes showed that the two copper(II) complexes exhibited more effective cytotoxic activity against HeLa and HEp-2 cells than the corresponding ligand. The entire biological activity results showed that the activity order was 1 < 2 < 3.     

Metal-based carboxamide-derived compounds endowed with antibacterial and antifungal activity

Abstract

A series of three bioactive thiourea (carboxamide) derivatives, N-(dipropylcarbamothioyl)-thiophene-2-carboxamide (L¹), N-(dipropylcarbamothioyl)-5-methylthiophene-2-carboxamide (L²) and 5-bromo-N-(dipropylcarbamothioyl)furan-2-carboxamide (L³) and their cobalt(II), copper(II), nickel(II) and zinc(II) complexes (1)–(12) have been synthesized and characterized by their IR,¹H-NMR spectroscopy, mass spectrometry and elemental analysis data. The Crystal structure of one of the ligand, N-(dipropylcarbamothioyl)thiophene-2-carboxamide (L¹) and its nickel(II) and copper(II) complexes were determined from single crystal X-ray diffraction data. All the ligands and metal(II) complexes have been subjected to in vitro antibacterial and antifungal activity against six bacterial species (Escherichia coli. Shigella flexneri. Pseudomonas aeruginosa. Salmonella typhi. Staphylococcus aureus and Bacillus subtilis) and for antifungal activity against six fungal strains (Trichophyton longifusus. Candida albicans. Aspergillus flavus. Microsporum canis. Fusarium solani and Candida glabrata). The in vitro antibacterial and antifungal bioactivity data showed the metal(II) complexes to be more potent than the parent ligands against one or more bacterial and fungal strains.     

Novel benzofuran-based sulphonamides as selective carbonic anhydrases IX and XII inhibitors: synthesis and in vitro biological evaluation

Abstract

Pursuing on our efforts toward searching for efficient hCA IX and hCA XII inhibitors, herein we report the design and synthesis of new sets of benzofuran-based sulphonamides (4a,b, 5a,b, 9a–c, and 10a–d), featuring the zinc anchoring benzenesulfonamide moiety linked to a benzofuran tail via a hydrazine or hydrazide linker. All the target benzofurans were examined for their inhibitory activities toward isoforms hCA I, II, IX, and XII. The target tumour-associated hCA IX and XII isoforms were efficiently inhibited with K _Is spanning in ranges 10.0–97.5 and 10.1–71.8?nM, respectively. Interestingly, arylsulfonehydrazones 9 displayed the best selectivity toward hCA IX and XII over hCA I (SIs: 39.4–250.3 and 26.0–149.9, respectively), and over hCA II (SIs: 19.6–57.1 and 13.0–34.2, respectively). Furthermore, the target benzofurans were assessed for their anti-proliferative activity, according to US-NCI protocol, toward a panel of sixty cancer cell lines. Only benzofurans 5b and 10b possessed selective and moderate growth inhibitory activity toward certain cancer cell lines.     

复合菌剂调控连作当归根围土壤养分及对产量的影响

【背景】连作可引起微生物群落结构失调,导致土壤环境恶化、养分循环不畅、当归[Angelica sinensis (Oliv.) Diels]产量降低,通过现代微生物技术改良土壤、消减连作障碍势在必行。【目的】于大田条件下,研究施用复合菌剂对当归根围土壤酶活、速效养分及产量的影响,明确增产机制,改进增产措施。【方法】利用溶磷圈法检测不同菌株溶磷活性、乙炔还原法检测固氮活性、试剂盒法检测过氧化物酶和硝化能力;复合菌剂T1[荧光假单胞菌(Pseudomonas fluorescens)CBS5、产碱假单胞菌(Pseudomonas alcaligenes) CBS7、嗜冷假单胞菌(Pseudomonas extremaustralis)CBSB、生枝动胶菌(Zoogloea ramigera) CBS4]和T2 (荧光假单胞菌CBS5、产碱假单胞菌CBS7、嗜冷假单胞菌CBSB)及对照CK (无菌马铃薯葡萄糖肉汤培养基)分别处理连作当归,分光光度法测定根围土壤及根中养分循环、转化相关酶活,氮、磷、钾速效养分含量;常规方法测产量;统计软件进行相关数据方差分析和主成分分析。【结果】产碱假单胞菌C...     

Nitrogen metabolism in the blue mycelia ofNeurospora crassa isolated from copper toxic cultures

The toxicity of copper on a sole nitrate medium containing KH₂PO₄ as the phosphate source has been studied inNeurospora crassa. Iron counteracted the copper toxicity by suppressing the copper uptake and restored complete growth at a lower iron-copper molar ratio. Nitrite reductase activity was inhibited (75%) in copper toxic cultures, while the nitrate reductase activity was unaltered. Nitrite accumulated in the medium; this indicated decreased conversion of nitrate to ammonia. Alanine transaminase was also inhibited in copper toxicity, resulting in an accumulation of keto acids. Iron could restore the nitrite reductase and the transaminase activities to about 70% of the control value. The accumulation of both nitrite and keto acids disappeared under conditions of reversal of copper toxicity by iron.     

Design,synthesis and evaluation of 3,4-dihydroxybenzoic acid derivatives as antioxidants,bio-metal chelating agents and acetylcholinesterase inhibitors

Abstract

Metal ions, especially copper, zinc and iron, play an important role in the neurodegeneration process because they can affect protein misfolding, leading to the formation of the amyloid deposits and oxidative stress leading to reactive oxygen species (ROS). Here we report the synthesis and evaluation as antioxidant and metal chelating agents of 3,4-dihydroxybenzoic acid derivatives. Synthesized compounds were tested by the 2,2-diphenyl-2-picrylhydrazyl (DPPH) method showing a radical scavenging ability (EC₅₀?=?0.093–0.118?μM) higher than Trolox used as reference. Furthermore, these compounds were able to bind both iron and copper, especially the iron (III), by the formation of hexa-coordinated complexes. Synthesized compounds were tested to evaluate their ability to inhibit acetyl- and butyryl-cholinesterase; the obtained results have demonstrated that they are selective inhibitors of AChE (K_i?=?1.5–18.9?μM) and result weakly active versus butyrylcholinesterase (BChE).     

硝酸盐对牛粪梭菌甲酸脱氢酶缺失型Wood-Ljungdahl途径固碳的影响

【背景】异于同型产乙酸菌通常利用Wood-Ljungdahl途径将2分子CO₂还原为1分子乙酰辅酶A,Clostridium bovifaecis缺失Wood-Ljungdahl途径甲基支路第1步将CO₂还原为甲酸的甲酸脱氢酶,需甲酸存在时将1分子甲酸和1分子CO₂还原为乙酰辅酶A发生葡萄糖的同型产乙酸型发酵。已有报道显示,硝酸盐也可作为同型产乙酸菌的电子受体,而且对不同同型产乙酸菌的代谢影响有所不同,然而硝酸盐对这种独特的甲酸脱氢酶缺失型Wood-Ljungdahl途径固碳的影响尚不清楚。【目的】探究硝酸盐对C.bovifaecis甲酸脱氢酶缺失型Wood-Ljungdahl途径固碳的影响。【方法】硝酸盐浓度分别为10 mmol/L和30 mmol/L时,以未添加硝酸盐为对照实验,研究C.bovifaecis在葡萄糖+甲酸+CO₂为基质条件下的细菌生长、底物消耗和产物生成情况。【结果】10 mmol/L和30 mmol/L硝酸盐存在时,主要产物乙醇浓度分别为5.80 mmol/L和1.66 mmo...     

Estimating local population size of the European Nightjar Caprimulgus europaeus using territory capture–recapture models

Capsule The capture–recapture model M(o) is an efficient way to estimate local population size.

Aims To test if a single capture–recapture modelling approach, combined with a simple survey method, can produce estimates of local population size from a dataset involving large‐scale multi‐observer surveys

Methods We sampled the presence of Nightjars in three separate sessions at three forests. Territory numbers were estimated using conventional territory‐mapping criteria. We ran different capture–recapture models to analyse the detection histories of territories obtained across the three sampling sessions and in the three different forests, using either only registrations of churring birds or all contacts.

Results The capture–recapture model M(o), assuming a constant detection probability, was the most efficient one to produce estimates of local population size. Using only two of the three sampling sessions gave less precise, though quite similar, estimates of the number of territories, with standard deviations representing 5–10% of the estimate values. However, this was reduced to 0.7–3.5%, i.e. three to seven times lower, when using the three sessions.

Conclusion Repeated sampling sessions to map territories can be efficiently used within the capture–recapture model M(o) to estimate detection probability and produce precise estimates of local population size.     

Surfactant–copper(II) Schiff base complexes: synthesis,structural investigation,DNA interaction,docking studies,and cytotoxic activity

A series of surfactant–copper(II) Schiff base complexes (1–6) of the general formula, [Cu(sal-R₂)₂] and [Cu(5-OMe-sal-R₂)₂], {where, sal?=?salicylaldehyde, 5-OMe-sal?=?5-methoxy- salicylaldehyde, and R₂?=?dodecylamine (DA), tetradecylamine (TA), or cetylamine (CA)} have been synthesized and characterized by spectroscopic, ESI-MS, and elemental analysis methods. For a special reason, the structure of one of the complexes (2) was resolved by single crystal X-ray diffraction analysis and it indicates the presence of a distorted square-planar geometry in the complex. Analysis of the binding of these complexes with DNA has been carried out adapting UV-visible-, fluorescence-, as well as circular dichroism spectroscopic methods and viscosity experiments. The results indicate that the complexes bind via minor groove mode involving the hydrophobic surfactant chain. Increase in the length of the aliphatic chain of the ligands facilitates the binding. Further, molecular docking calculations have been performed to understand the nature as well as order of binding of these complexes with DNA. This docking analysis also suggested that the complexes interact with DNA through the alkyl chain present in the Schiff base ligands via the minor groove. In addition, the cytotoxic property of the surfactant–copper(II) Schiff base complexes have been studied against a breast cancer cell line. All six complexes reduced the visibility of the cells but complexes 2, 3, 5, and 6 brought about this effect at fairly low concentrations. Analyzed further, but a small percentage of cells succumbed to necrosis. Of these complexes (6) proved to be the most efficient aptotoxic agent.     

Biomass growth variation and phytoextraction potential of four Salix varieties grown in contaminated soil amended with lime and wood ash

Abstract

In a greenhouse experiment, plant growth and copper (Cu) and zinc (Zn) uptake by four Salix cultivars grown in Cu and Zn contaminated soils collected from a mining area in Finland were tested to assess their suitability for phytoextraction. The cultivars displayed tolerance to heavily contaminated soils throughout the experiment. After uptake, total mean Cu concentrations in the leaves, shoots and roots in all cultivars and treatments ranged from 163 to 474?mg kg^?1 and mean Zn concentrations ranged from 776 to 1823?mg kg^?1. Lime and wood ash addition increased dry biomass growth (25–43%), chlorophyll fluorescence (Fv/Fm) values (3–6%), the translocation factor (TF) (15–60% for Cu; 10–25% for Zn), the bio-concentration factor (BCF) (40–85% for Cu; 70–120% for Zn), and metal uptake (55–70% for Cu; 50–65% for Zn) compared to unamended treatment across all cultivars. The results revealed that Salix cultivars have the potential to take up and accumulate significant amounts of Cu and Zn. Cultivar Klara (Salix viminalis × S. schwerinii × S. dasyclados) was found to be the most effective cultivar for phytoextraction since it displayed greater dry biomass production, Fv/Fm, TF, BCF values and uptake percentage rates of Cu and Zn compared to the other three cultivars. This study indicates that further research is needed to clarify the wider phytoextraction capabilities of different Salix cultivars.     

Effect of DCMU, Simazine and Atrazine on Nitrate Reductase Activity in Hordeum vulgare in vitro

The effect of three herbicides—DCMU (1,1-dimethyl-3- (3,4-dichlorophenyl) -urea), Simazine (2,4-bis(ethylamino)- 6-chloro-s-triazine), and Atrazine (2-chloro-4-ethylamino-6-iso-propylamino-5-triazine)—on the induction of nitrate reduc–tase and its in vivo activity was studied in detached leaves of Hordeum vulgare L. All increased both extractable nitrate reductase activity and nitrate content. The increases occurred at optimum temperatures for growth and at several concentrations of nitrate. It was also determined that the herbicides did not protect the enzyme against inactivation in vivo. Although the extractable nitrate reductase was greater, the in vivo activity of nitrate reductase was decreased in the presence of the herbicides resulting in a higher internal concentration of nitrate. Since in viva nitrate reduction is dependent upon photosynthesis it is reasonable that reduction is decreased by these known inhibitors of photosynthesis. Hence, the effect of the inhibitors on induction of nitrate reductase activity may be secondary. The higher concentration of nitrate resulting from a decreased rate of in vivo reduction in the presence of the inhibitors could conceivably be responsible for the greater corutent of nitrate reductase.     

Nitrogen‐isotope fractionation in the nitrate respiration by the marine bacterium Serratia marinorubra

Abstract

The isotopic composition (δ¹⁵N) of nitrite produced during nitrate respiration by both growing and washed cells of the marine bacterium, Serratia marinorubra, was determined. In both the growing and washed cells, δ¹⁵N of the nitrite changed considerably with time. At least two reaction steps, producing different isotope effects (active transport of nitrate across membranes and reduction of nitrate to nitrite), appear to be involved. With washed cells, a fractionation factor as high as 1.039 was obtained—the highest ever reported for biologicalnitrate reduction. The physiological state of nitrate‐respiring bacteria in oxygen‐depleted subsurface waters of the sea is discussed from the viewpoint of isotope fractionation.     

Design,synthesis, and biological properties of triazole derived compounds and their transition metal complexes

Triazole derived Schiff bases and their metal complexes (cobalt(II), copper(II), nickel(II), and zinc(II)) have been prepared and characterized using IR, ¹H and ¹³C NMR, mass spectrometry, magnetic susceptibility and conductivity measurements, and CHN analysis data. The structure of L², N-[(5-methylthiophen-2-yl)methylidene]-1H-1,2,4-triazol-3-amine, has also been determined by the X-ray diffraction method. All the metal(II) complexes showed octahedral geometry except the copper(II) complexes, which showed distorted octahedral geometry. The triazole ligands and their metal complexes have been screened for their in vitro antibacterial, antifungal, and cytotoxic activity. All the synthesized compounds showed moderate to significant antibacterial activity against one or more bacterial strains. It is revealed that all the synthesized complexes showed better activity than the ligands, due to coordination.     

Steady-state nutrition and growth responses of Betula pendula to different relative supply rates of copper

In a series of experiments on the growth and nutrition of copper-limited birch (Betula pendula Roth) plants, growth was controlled by the relative addition rate of copper, R_Cu (d^–1). This was 0·05, 0·10, 0·15 or 0·20 d^–1 with free access to all other nutrients. An additional treatment provided free access to all nutrients. The pH in the nutrient solution was ≈ 4·5 and conductivity was 100 μS cm^–1. At steady-state growth, there was a linear relationship between the relative growth rate, R_G, and R_Cu. The [Cu] of the plants ranged from 2·4 to 2·7 μg g^–1 dry mass (DM) in all treatments with limiting R_Cu and was ≈ 28 μg g^–1 in the free access treatment. The plants showed specific copper deficiency symptoms at limitation. Total non-structural carbohydrate concentrations and the fraction of plant DM partitioned to roots was much less at copper limitation than at free access. The uptake rate of copper per unit root growth rate, dCu/dW_r (μmol g^–1 root DM) was unaffected by the copper supply. Low rates of plant growth at copper limitation were associated with high values of specific leaf area (SLA; 47 m² kg^–1) and leaf area ratio (LAR; 28 m² kg^–1 plant DM) but lower values of net assimilation rate (NAR; 2·5 kg m^–2 leaf DM d^–1) than were found at free access, 28 m² kg^–1 (SLA), 17 m² kg^–1 DM (LAR) and 14 kg m^–2 leaf DM d^–1 (NAR), respectively. It is not obvious from the present data how the growth response can help alleviate copper limitation in the field.