Equimolar Research Articles

Intramolecular Thiol- and Selenol-Assisted Delivery of Hydrogen Sulfide.

Arylthioamides have been frequently employed to assess the chemical biology and pharmacology of hydrogen sulfide (H2 S). From this class of donors, however, extremely low H2 S releasing efficiencies have been reported and proper mechanistic studies have been omitted. Consequently, millimolar concentrations of arylthioamides are required to liberate just trace amounts of H2 S, and via an unidentified mechanistic pathway, which obfuscates the interpretation of any biological activity that stems from their use. Herein, we report that H2 S release from this valuable class of donors can be markedly enhanced through intramolecular nucleophilic assistance. Specifically, we demonstrate that both disulfide- and diselenide-linked thioamides are responsive to biologically relevant concentrations of glutathione and release two molar equivalents of H2 S via an intramolecular cyclization that significantly augments their rate and efficiency of sulfide delivery in both buffer and live human cells.

Intramolecular Thiol‐ and Selenol‐Assisted Delivery of Hydrogen Sulfide

AbstractArylthioamides have been frequently employed to assess the chemical biology and pharmacology of hydrogen sulfide (H2S). From this class of donors, however, extremely low H2S releasing efficiencies have been reported and proper mechanistic studies have been omitted. Consequently, millimolar concentrations of arylthioamides are required to liberate just trace amounts of H2S, and via an unidentified mechanistic pathway, which obfuscates the interpretation of any biological activity that stems from their use. Herein, we report that H2S release from this valuable class of donors can be markedly enhanced through intramolecular nucleophilic assistance. Specifically, we demonstrate that both disulfide‐ and diselenide‐linked thioamides are responsive to biologically relevant concentrations of glutathione and release two molar equivalents of H2S via an intramolecular cyclization that significantly augments their rate and efficiency of sulfide delivery in both buffer and live human cells.

Chemical hydrolysis of hemicellulose from sugarcane bagasse. A comparison between the classical sulfuric acid method with the acidic ionic liquid 1-ethyl-3-methylimidazolium hydrogen sulfate

Dilute sulfuric acid and acidic ionic liquids are pretreatment methods used to selectively hydrolyze hemicellulose from lignocellulosic biomasses. In this work, a comparison between these techniques is carried out by treating sugarcane bagasse both with 1-ethyl-3-methylimidazolium hydrogen sulfate at different ionic-liquid and water contents and with H 2 SO 4 at the same conditions and equivalent ionic liquid molar contents. Results from the use of ionic liquid showed that it was possible to tune the biomass treatment either to achieve high hemicellulose hydrolysis yields of 72.5 mol% to very low furan and glucose co-production, or to obtain furfural at moderate yields of 18.7 mol% under conditions of low water concentration. In comparison to the use of ionic liquid, sulfuric acid pretreatment increased hemicellulose hydrolysis yields by 17%, but the 8.6 mol% furfural yield was also higher, and these yields were obtained at high water concentration conditions. Besides, no such tuning ability of the biomass treatment conditions can be made.

Cell adaptation of the extremophilic red microalga Galdieria sulphuraria to the availability of carbon sources.

Global energy demand and fossil fuels impact on climate can be partially managed by an increase in the use of biofuels for transports and industries. Biodiesel production is generally preceded by a transesterification process of the green biomass triacylglycerols that generates large amounts of glycerol as a by-product. In this study, the extremophilic red microalga Galdieria sulphuraria 074W was cultivated in heterotrophy. The microalgal growth parameters and biomass composition were compared when grown on an equivalent molar concentration of carbon of either glucose or glycerol as unique carbon source. The maximal biomass reached in these two conditions was not significantly different (∼2.5 g.L–1). Fatty acid profile, protein and storage carbohydrate contents were also statistically similar, irrespectively of the metabolized carbon source. We also observed that the pigment content of G. sulphuraria cells decreased during heterotrophic growth compared to photoautotrophic cultivated cells, and that this diminution was more important in the presence of glucose than glycerol: cells were yellowish in the presence of glucose and green in the presence of glycerol. The pigmentation was restored when glucose was totally consumed in the medium, suggesting that the presence of glucose repressed pigment synthesis. Based on this observation, a transcriptome analysis was performed in order to better understand the mechanisms involved in the loss of color mediated by darkness and by glucose in G. sulphuraria. Three conditions were analyzed: heterotrophy with glycerol or glucose and phototrophy. This allowed us to understand the transcriptional response of cells to light and dark environments both at the nuclear and chloroplast levels, and to show that transcription of gene families, acquired by horizontal gene transfer, such as sugar, amino acid, or acetate transporters, were involved in the response to the availability of different (in)organic sources.

Mechanical and thermal behaviors of Ti36-Al16-V16-Fe16-Cr16 high entropy alloys fabricated by spark plasma sintering: An advanced material for high temperature/strength applications

Conventional superalloys possess high strength, high oxidation resistance and high creep resistance. Nonetheless, some lose strength at elevated temperatures, while others suffer high temperature oxidation and creep. This work was aimed at developing high entropy alloy (HEA) of Ti36-Al16-V16-Fe16-Cr16 at near equi molar configuration using spark plasma sintering technique which would be able to address the challenges of conventional superalloys. The powders were mixed with Turbular mixer at 69 rpm for 10 h. The sintering was carried out with the same sintering pressure of 40 MPa, time of 10 min, heating rate of 100°C/mins on all the samples. Only the sintering temperature was varied. The temperatures used included 700°C, 800°C, 900°C, 1000°C and 1100°C, respectively. The powders and sintered samples were characterized with Scanning electron microscopy connected to Energy Dispersive Spectroscopy and X-ray diffractometer. The mechanical properties were tested with Nano indenter using ASTM D785 standard; while the thermal stability was investigated with thermogravimetric analyzer. Results showed that HEA sintered at 1000°C possessed the best nanomechanical, thermal and microstructural properties while that sintered at 700°C had the weakest properties. The best developed alloy had an improved elastic modulus of 671.17 ± 50 GPa and 930.12 ± 38 GPa at darker flakey phase and white phase, respectively. It had creep resistance of 1.82%, densification of 98.96% and porosity of 1.04%. It was concluded that the developed alloy can perform much better than most superalloys in high temperature and high strength and applications.

Dinuclear bismuth(III) complex constructed by isoniazid‐derived Schiff base: Synthesis, crystal structure, and biological activity

A new bismuth(III) Schiff‐base complex [Bi2(HL)2(NO3)4(CH3OH)]•2CH3OH was prepared by reaction of the equivalent molar of Schiff‐base ligand [H2L = (E)‐N′‐(2‐hydroxy‐4‐methoxybenzylidene)isonicotinohydrazide] and Bi (NO3)3•5H2O with the assistance of mannitol. The complex was structurally characterized by elemental analysis, spectroscopic methods (FT‐IR, MS, 1HNMR, and 13CNMR) and single crystal X‐ray diffraction. The molecular structure of the complex reveals that the ligand forms a 1:1 complex with bismuth(III) ion. It is composed of two 7‐coordinated bismuth(III) ions, two tetradentate O2N‐donor ligands, four nitrate ions, and three methanol molecules. The complex and its free ligand were evaluated against gram‐positive bacteria (Staphylococcus aureus, Bacillus subtilis) and gram‐negative bacteria (Escherichia coli, Pseudomonas aeruginosa). The complex was more active than the ligand against all bacterial strains. Their cytotoxic activity was also investigated against SNU‐16 cell. The complex is approximately three times more potent than the ligand, with the IC50 values 0.35 and 1.18 μM for the complex and its ligand, respectively.

A54145 Factor D Is Not Less Susceptible to Inhibition by Lung Surfactant than Daptomycin.

A54145 factor D (A5D) is a cyclic lipopeptide antibiotic that shares several structural and mechanistic features with the clinically important antibiotic daptomycin, such as their requirement for calcium and phosphatidylglycerol (PG) for activity. Studies by others have suggested that daptomycin's activity is strongly inhibited by lung surfactant while A5D's activity is not. This finding has inspired efforts, albeit unsuccessful, to develop an A5D analogue that is highly active in the presence of lung surfactant and can be used for treating community acquired pneumonia (CAP). Here we demonstrate that A5D, like daptomycin, has a strong preference for the 1,2-diacyl-sn-glycero-3-phospho-1'-sn-glycerol stereoisomer (2R,2'S configuration) of PG. This PG stereoisomer was determined to be the only stereoisomer of PG in lung surfactant. Both antibiotics are completely antagonized by approximately 1-2 mol equiv of 2R,2'S-PG. Studies performed in the presence of lung surfactant revealed that the antagonism of these peptides by surfactant is mainly due to their interaction with PG and that A5D is not significantly less susceptible to inhibition by lung surfactant than daptomycin.

Poly(trehalose methacrylate) as an Excipient for Insulin Stabilization: Mechanism and Safety.

Insulin, the oldest U.S. Food and Drug Administration (FDA)-approved recombinant protein and a World Health Organization (WHO) essential medicine for treating diabetes globally, faces challenges due to its storage instability. One approach to stabilize insulin is the addition of poly(trehalose methacrylate) (pTrMA) as an excipient. The polymer increases the stability of the peptide to heat and mechanical agitation and has a low viscosity suitable for injection and pumps. However, the safety and stabilizing mechanism of pTrMA is not yet known and is required to understand the potential suitability of pTrMA as an insulin excipient. Herein is reported the immune response, biodistribution, and insulin plasma lifetime in mice, as well as investigation into insulin stabilization. pTrMA alone or formulated with ovalbumin did not elicit an antibody response over 3 weeks in mice, and there was no observable cytokine production in response to pTrMA. Micropositron emission tomography/microcomputer tomography of 64Cu-labeled pTrMA showed excretion of 78–79% ID/cc within 24 h and minimal liver accumulation at 6–8% ID/cc when studied out to 120 h. Further, the plasma lifetime of insulin in mice was not altered by added pTrMA. Formulating insulin with 2 mol equiv of pTrMA improved the stability of insulin to standard storage conditions: 46 weeks at 4 °C yielded 87.0% intact insulin with pTrMA present as compared to 7.8% intact insulin without the polymer. The mechanism by which pTrMA-stabilized insulin was revealed to be a combination of inhibiting deamidation of amino acid residues and preventing fibrillation, followed by aggregation of inactive and immunogenic amyloids all without complexing insulin into its hexameric state, which could delay the onset of insulin activity. Based on the data reported here, we suggest that pTrMA stabilizes insulin as an excipient without adverse effects in vivo and is promising to investigate further for the safe formulation of insulin.

An Acyclic Silylone Stabilized by Mesoionic Carbene

AbstractThe synthesis and characterization of an acyclic silylone (MIC)2Si 2 (MIC=1,3‐di(2,6‐diisopropylphenyl)‐4‐phenyl‐1,2,3‐triazol‐5‐ylidene) supported by a mesoionic carbene was reported. 2 was obtained by the reduction of (MIC)SiCl4 1 with 4 molar equivalents of potassium graphite in toluene at −10 °C. Theoretical calculations on 2 reveal that the silicon center is highly electron‐rich and bears two lone‐pairs of electrons. Preliminary reactivity study shows that 2 can coordinate to two CuCl molecules to furnish a dinuclear copper(I) complex (MIC)2Si(CuCl)2 3.

Cu-Catalyzed Chan-Evans-Lam Coupling Reactions of 2-Nitroimidazole with Aryl Boronic Acids: An Effort toward New Bioactive Agents against S. pneumoniae.

The coupling of phenylboronic acids with poorly-activated imidazoles is studied as a model system to explore the use of copper-catalyzed Chan-Evans-Lam (CEL) coupling for targeted C-N bond forming reactions. Optimized CEL reaction conditions are reported for four phenanthroline-based ligand systems, where the ligand 4,5-diazafluoren-9-one (dafo, L2) with 1 molar equivalent of potassium carbonate yielded the highest reactivity. The substrate 2-nitroimidazole (also known as azomycin) has documented antimicrobial activity against a range of microbes. Here N-arylation of 2-nitroimidazole with a range of aryl boronic acids has been successfully developed by copper(II)-catalyzed CEL reactions. Azomycin and a range of newly arylated azomycin derivatives were screened against S. pneumoniae, where 1-(4-(benzyloxy)phenyl)-2-nitro-1H-imidazole (3d) was demonstrated to have a minimal inhibition concentration value of 3.3 μg/mL.

Efficient biosynthesis of D-mannitol by coordinated expression of a two-enzyme cascade

D-mannitol is widely used in the pharmaceutical and medical industries as an important precursor of antitumor drugs and immune stimulants. However, the cost of the current enzymatic process for D-mannitol synthesis is high, thus not suitable for commercialization. To address this issue, an efficient mannitol dehydrogenase LpGDH used for the conversion and a glucose dehydrogenase BaGDH used for NADH regeneration were screened, respectively. These two enzymes were co-expressed in Escherichia coli BL21(DE3) to construct a two-enzyme cascade catalytic reaction for the efficient synthesis of d-mannitol, with a conversion rate of 59.7% from D-fructose achieved. The regeneration of cofactor NADH was enhanced by increasing the copy number of Bagdh, and a recombinant strain E. coli BL21/pETDuet-Lpmdh-Bagdh-Bagdh was constructed to address the imbalance between cofactor amount and key enzyme expression level in the two-enzyme cascade catalytic reaction. An optimized whole cell transformation process was conducted under 30 ℃, initial pH 6.5, cell mass (OD600) 30, 100 g/L D-fructose substrate and an equivalent molar concentration of glucose. The highest yield of D-mannitol was 81.9 g/L with a molar conversion rate of 81.9% in 5 L fermenter under the optimal conversion conditions. This study provides a green and efficient biotransformation method for future large-scale production of D-mannitol, which is also of great importance for the production of other sugar alcohols.

Receptor-Targeted Dual pH-Triggered Intracellular Protein Transfer.

Protein therapeutics are of widespread interest due to their successful performance in the current pharmaceutical and medical fields, even though their broad applications have been hindered by the lack of an efficient intracellular delivery approach. Herein, we fabricated an active-targeted dual pH-responsive delivery system with favorable tumor cell entry augmented by extracellular pH-triggered charge reversal and tumor receptor targeting and pH-controlled endosomal release in a traceless fashion. As a traceable model protein, the enhanced green fluorescent protein (eGFP) bearing a nuclear localization signal was covalently coupled with a pH-labile traceless azidomethyl-methylmaleic anhydride (AzMMMan) linker followed by functionalization with different molar equivalents of two dibenzocyclooctyne-octa-arginine-cysteine (DBCO-R8C)-modified moieties: polyethylene glycol (PEG)-GE11 peptide for epidermal growth factor receptor-mediated targeting and melittin for endosomal escape. The cationic melittin domain was masked with tetrahydrophthalic anhydride revertible at mild acidic pH 6.5. At the optimally balanced ratio of functional units, the on-demand charge conversion at tumoral extracellular pH 6.5 in combination with GE11-mediated targeting triggered enhanced electrostatic cellular attraction by the R8C cell-penetrating peptides and melittin, as demonstrated by strongly enhanced cellular uptake. Successful endosomal release followed by nuclear localization of the eGFP cargo was obtained by taking advantage of melittin-mediated endosomal escape and rapid traceless release from the AzMMMan linker. The effectiveness of this multifunctional bioresponsive system suggests a promising strategy for delivery of protein drugs toward intracellular targets. A possible therapeutic relevance was indicated by an example of cytosolic delivery of cytochrome c initiating the apoptosis pathway to kill cancer cells.

DC Surface Flashover Characteristics of Polyimide Containing Polyhedral Oligomeric Silsesquioxane (POSS) in the Main Chains under Vacuum.

Polyimide, which is widely used to insulate power equipment operating in a vacuum environment, is prone to insulation failure due to surface flashover. Using POSS to modify it is an effective solution. This paper focuses on the study of DC surface flashover characteristics in vacuum of POSS/polyimide composite film, by introducing 1%, 3%, 5% equivalent mole content of POSS into polyimide, and conducting a surface flashover characteristics test in vacuum together with pure polyimide. The physical and chemical properties of the composite films were tested utilizing Fourier transform infrared spectroscopy and ultraviolet–visible spectroscopy. Combined with resistivity, SEM, and other test techniques, the influence mechanism of POSS molecular modification on DC surface flashover characteristics of polyimide films in vacuum was initially revealed. The results showed that after the introduction of POSS, the overall functional group structure of polyimide remained unchanged, the intermolecular charge transfer complexation was inhibited, and the transmittance of the film increased. The thermal conductivity and thermogravimetric temperature of the film are improved to a certain extent, and the mechanical properties are slightly decreased. With the increase of the introduced POSS content, the dielectric strength of the composite film is also enhanced. The surface flashover voltage of the composite film with a POSS content of 5% is 17.5 kV in vacuum, which is 30.5% higher than that of the pure film. Further analysis shows that the introduction of POSS will reduce the resistivity of the composite film, accelerate the dissipation of surface charges, and increase the flashover voltage. In addition, POSS forms a uniformly distributed Si-O-Si cage-like structure through molecular modification. When the surface of the film is damaged, SiOx inorganic flocculent particles are generated, which can not only scatter electrons, but also shallow the depth of trap energy level and accelerate the dissipation rate of surface charge, thus increasing the flashover voltage.

Abstract 3094: Proteomic profiling of cholangiocarcinoma predicts response to a novel small molecule inhibitor in preclinical models

Abstract Background: Cholangiocarcinoma is an aggressive malignancy with limited systemic therapeutics. We have recently identified LCK, a non-receptor tyrosine kinase, as a potential therapeutic target in select subtypes of cholangiocarcinoma. Proteomic profiling in other cancer types has proven beneficial in predicting response to systemic therapies. Herein, we present proteomic profiling of cholangiocarcinoma can predict sensitivity to a novel LCK inhibitor in patient derived xenograft models. Methods: Proteins from 28 unique cholangiocarcinoma patient derived xenograft models (PDX) were isolated, labeled with tandem mass tags (TMT) and then analyzed by liquid chromatography and mass spectroscopy (LC/MS). Phosphopeptides were separately evaluated both by Immobilized Metal Affinity Chromatography and pY-enrichment techniques. Following normalization, the global proteome, serine/threonine phosphoproteome, and tyrosine phosphoproteome were analyzed and a proteomic signature was created for each tumor. These signatures were compared to PDX models with known response profiles to NTRC0652-0, an LCK inhibitor (1 resistant and 1 sensitive). The top 200 differentially abundant proteins (log2FC 2.6) were then utilized to develop a sensitive and a resistant signature. Correlation indices were then calculated across the 28 PDX model library. An additional predicted resistant and predicted sensitive model was expanded. Tumor bearing mice were randomized based on tumor volume to either treatment with NTRC (30mg/kg PO daily), n=5, or vehicle, n=4, (10% Kolliphor, 10% DMSO, 80% Water, 2 mol equivalents HCl). Tumors were measured weekly with calipers and then weighed at the end of the study. Results: In the top 200 differentially abundant proteins that represented the proteomic signature there was over representation of proteins with decreased abundance. There were only 12 proteins with higher abundance in the sensitive model as compared to the resistant. Utilizing the signature developed from the global proteomics data, nine tumors were predicted to be sensitive while 17 were predicted to be resistant to NTRC. PDX115 is a an intrahepatic CCA PDX known to contain an IDH1 mutation and was predicted to be resistant by modeling. The model was resistant to single agent NTRC with no demonstrable effect on tumor growth in vivo. PDX175 is a distal CCA PDX and was predicted to be sensitive by modeling. In vivo growth was inhibited by NTRC as compared to vehicle treated mice following two weeks of treatment (983% vs 435%, p=0.03). Additionally, final tumor weight was significantly lower in NTRC treated mice (0.651 g vs 0.317 g, p=0.04). Conclusion: Cholangiocarcinoma proteomic signatures can be used to predict therapeutic response to a novel LCK inhibitor in preclinical models. Whether or not this could be applied to other treatment modalities in cholangiocarcinoma remains to be determined. Citation Format: Ryan Watkins, Roberto Alva-Ruiz, Caitlin Conboy, Dong-Gi Mun, Erik Jessen, Diep Vu, Jos de Man, Rogier Buijsman, Akhilesh Pandey, Mitesh Borad, Gregory Gores, Rory Smoot. Proteomic profiling of cholangiocarcinoma predicts response to a novel small molecule inhibitor in preclinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3094.

Contributions of intestine and liver to the absorption and disposition of FZJ-003, a selective JAK1 inhibitor with structure modification of filgotinib

FZJ-003 is a selective Janus kinase 1 (JAK1) inhibitor with structural modification of filgotinib for rheumatoid arthritis (RA) treatment. In this study, a series of in vivo and in vitro experiments were conducted to investigate the specific contribution of the intestine and liver to the disposition of FZJ-003 compared with filgotinib. Results showed that FZJ-003 exhibited over 2-fold higher systemic exposure and lower clearance than those of filgotinib, after intravenous or intragastric administration at the equivalent mole dose level to conscious rats. In anesthetized rats treated with different dosing routes, FZJ-003 exhibited higher intestinal bioavailability (Fa·Fg, 98.47 vs 34.54%) but lower hepatic bioavailability (Fh, 61.45 vs 92.07%). Permeability test in Caco-2 cells indicated that FZJ-003 was probably transported by passive diffusion (efflux ratio 1.37 < 2, indicating the approximately equivalent Papp values in two directions) with a little higher permeability (Papp,AP-to-BL, 1.42 × 10−6vs 1.01 × 10−6 cm·s−1, FZJ-003 vs filgotinib). Metabolic studies in pre-systemic incubation systems showed that FZJ-003 experienced more NADPH-dependent metabolism, especially in hepatic microsomes fractions. Unlike filgotinib, there was no obvious amide-hydrolyzed metabolite of FZJ-003 detected throughout the pre-systemic metabolic sites. Collectively, these data suggest that the higher systemic exposure of FZJ-003 than filgotinib is mainly attributed to the higher intestinal bioavailability including bypassing the amide hydrolysis and possible efflux by intestinal epithelial cells, which strongly support the structural design purpose in terms of pharmacokinetics.

Nanoporous Vesicular Membranes of Amphiphilic Polymers Containing Trans / Cis Isomers

Nanoporous Vesicular Membranes of Amphiphilic Polymers Containing <i>Trans</i> / <i>Cis</i> Isomers

Comparative study of palladium(II) complexes bearing tridentate ONS and NNS Schiff base ligands: Synthesis, characterization, DFT calculation, DNA binding, bioactivities, catalytic activity, and molecular docking

Two palladium (II) Schiff base complexes were prepared by using equivalent molar of Schiff base ligand [L1= (E)-2-(((2-(benzylthio)phenyl)imino)methyl)naphthalen-1-ol and L2= (E)-N-(2-(benzylthio)phenyl)-1-phenyl-1-(pyridin-2-yl)methanimine] and sodium tetrachloropalladate. The structure of ligands and complexes were characterized by physicochemical and spectroscopic analyses. The results suggested that the Pd(II) complexes have a distorted square planar geometry when coordinated to the tridentate ONS from L1 and the NNS donor ligand from L2. Electronic absorption and spectrofluorometric measurements were employed to investigate the DNA binding of ligands and their associated complexes with CT-DNA. DFT calculations were used to optimize the geometric structures and calculate the electronic and structural properties of the synthesized compounds. NBO analysis was also performed in combination with the TD-DFT method. Moreover, to study the reactivity and bioactivity, the synthesized compounds were tested for in-vitro antioxidant activity by utilizing the DPPH method, in-vitro anti-inflammatory activity using protein denaturation method, and in-vitro anti-diabetic activity employing α-glucosidase and α-amylase enzymes. The results reflect that PdL1 is more biologically potent than PdL2 or other related palladium complexes, as discussed in the literature. The binding mechanism of the synthesized compounds with CT-DNA, α-glucosidase, and α-amylase, was investigated using molecular docking experiments. In addition to these, the catalytic activity of palladium metal complexes (PdL1 and PdL2) was evaluated for the Suzuki-Miyaura reaction for comparisons.

Synthesis, spectroscopic, anti-bacterial activity, molecular docking, ADMET, toxicity and DNA binding studies of divalent metal complexes of pyrazole-3-one azo ligand

Treatment equivalent molar of pyrazole-3-one azo (HPyoz) ligand with divalent metal ions {Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II)} afforded complexes of the chemical formula [MCl2(H2O)2(HPyoz)] {Co(II), Ni(II), and Cu(II)} or [MCl2(HPyoz)] {Zn(II), Cd(II) and Hg(II)}. The prepared complexes were characterized using IR, 1H, 13C NMR, Uv-visible spectra, xrd, SEM, conductance, and magnetic measurements. The results refer to that the HPyoz ligand behaves as bidentate via the nitrogen of azo group and oxygen of carbonyl group to afforded an octahedral complexes around transition metal ion {Co(II), Ni(II), and Cu(II)} or tetrahedral geometry around 12B group ions {Zn(II), Cd(II) and Hg(II)}. The results obtained from xrd and SEM images unequivocally declared the nano-sized of the prepared complexes. The lately studied compounds were examined for anti-bacterial activities towards four pathogenic species of bacteria. Molecular docking had been done based on screening against different targets, that show the good binding affinity of tested compounds with nucleoside diphosphate kinase (target site PDB ID: 3Q89), it's an important enzyme that generates nucleoside triphosphates (NTPs) or their deoxy derivatives by terminal phosphor-transfer from an NTP such as ATP or GTP to any nucleoside diphosphate or its deoxy derivative. As NTPs, particularly GTP, are important for cellular macromolecular synthesis and signaling mechanisms, Ndk plays an important role in bacterial growth, signal transduction and pathogenicity. In addition, The DNA binding properties of prepared complexes were evaluated. The intrinsic binding constant is calculated as 6.79 × 105, 4.72 × 105, 1.89 × 105 and 4.12 × 105M − 1 for the Ni-complex, Co-complex, Cu-complex and Zn-complex, and these results establish good binding characteristics of the prepared complexes with DNA

Molybdenum active sites implanted defective UiO-66(Zr) for cyclohexene epoxidation: Activity and kinetics investigation

Defect engineering is a versatile method to modulate structure and performance of crystalline materials yet remain sophisticated. Herein, Zr-based metal organic frameworks (i.e., UiO-66) featuring controlled structural defects and single Mo active sites, namely Mo@UiO-66-xy (x represented molar equivalents and y denoted the modulator, acetic acid or formic acid, with respect to the linker), were synthesized to systematically conduct activity and kinetics investigation on microscopic level. It was determined that the predominant defects, missing-cluster defects, could be tuned to a large extent via altering molar equivalents of formic acid not acetic acid. Further, it was established that intrinsic Lewis acid acidity was positively correlated with formic acid concentration. All Mo@UiO-66-xy exhibited catalytic activity in cyclohexene epoxidation and Mo@UiO-66-100for showed the highest catalytic performance due to its relative strong Lewis acid acidity and suitable specific surface area / porosity-derived attractive high Mo sites-dispersion and mass-transfer property. Additionally, for the first time, a kinetic measurement that considered two reaction pathways and all products was performed as a function of reaction temperature to evaluate activation barrier for cyclohexene epoxidation. That was, cyclohexene epoxidation to epoxide activation energies determined for direct and radical routes were 46.12 and 102.46 kJ mol−1, respectively, and Mo@UiO-66-100for was inclined to act along direct pathway to stimulate cyclohexene epoxidation.

Release of poly- and perfluoroalkyl substances from finished biosolids in soil mesocosms

Finished biosolids were collected and characterized from seven municipal water resource recovery facilities. Poly- and perfluoroalkyl substances (PFAS) for the 54 quantified in the biosolids ranged from 323 ± 14.1 to 1100 ± 43.8 µg/kg (dry weight basis). For all biosolids, greater than 75% of the PFAS fluorine mass was associated with precursors. Di-substituted polyfluorinated phosphate esters (diPAPs) were the most abundant PFAS identified in the biosolids. The total oxidizable precursor assay on biosolids extracts generally failed to quantify the amount of precursors present, in large part due to the fact that diPAPS were not fully transformed during the TOP assay. Outdoor biosolids column leaching experiments intended to simulate biosolids land application showed sustained PFAS leaching over the 6-month study duration. Perfluoroalkyl acid (PFAA) concentrations in leachate, when detected, typically ranged in the 10 s to 100 s of ng/L; no diPAPs were detected in the leachate. The PFAA leaching from the biosolids exceeded the PFAA mass initially present in the biosolids (typically by greater than an order of magnitude), but the cumulative PFAA mass leached did not exceed the molar equivalents that could be explained by transformation of quantified precursors. These results highlight the importance of PFAA precursors initially present in biosolids and their contribution to long term leaching of PFAAs from land-applied biosolids.