Selective Hydrolysis of Ovalbumin by Zr-Based Lacunary Polyoxotungstate in Surfactant Solutions.

This study aims to design an artificial metalloprotease based on a Zr-containing polyoxometalate Na8[Zr(W5O18)2] [Zr(W5)2] for the hydrolysis of ovalbumin (OVA) in the presence of different surfactants, which can be used in many areas of the biological and medical sciences, particularly for targeted proteolytic drug design. For this reason, parameters, including the free energy of binding, the chemical nature of amino acid residues, secondary structures, and electrostatic potentials, of Zr(W5)2-OVA and Zr(W5)2-OVA-surfactant were analyzed by molecular docking simulations. The investigations showed that the presence of surfactants decreases the binding affinity of Zr(W5)2 for OVA amino acids, and hydrogen bonds and van der Waals interactions are formed between Zr(W5)2 and OVA amino acids. Additionally, GROMACS further illustrated the significance of SDS and CTAB surfactants in influencing the conformational changes of the OVA that lead to selective protein hydrolysis. In agreement with molecular dynamics simulation results, the experimental analysis showed more protein hydrolysis for the Zr(W5)2-OVA-surfactant systems. For instance, circular dichroism spectroscopy indicated that Zr(W5)2-OVA-CTAB and Zr(W5)2-OVA-TX-100 were more hydrolytically efficient due to the increased level of ß-structures rather than α-chains, which showed that surfactants can facilitate the accessibility of Zr(W5)2 to the cleavage sites by inducing partial unfolding of the OVA structure.

Opioid Drug Detection in Hair Samples Using Polyoxometalate-Based Frameworks.

A series of two-dimensional (2D) polyoxometalate-based frameworks, [Ln3(PDA)3(H2O)6(PMo12O40)]·xH2O (Ln = La (1); Ce (2); Pr (3); Nd (4); PDA = 1,10-phenanthroline-2,9-dicarboxylate), have been synthesized and structurally characterized by various analytical techniques. Single-crystal X-ray diffraction reveals that 1-4 have a unique 2D layer structure in which Keggin anions have coordinated upward and downward the plane, and this feature makes them suitable candidates for surface binding of common drugs via supramolecular and electrostatic interactions. Also, the ability of 1-4 (as the first polyoxomolybdate-containing frameworks) as sorbents for the extraction and quantitative determination of opioid drugs (morphine, methadone, and pethidine) was investigated by using dispersive micro-solid-phase extraction (D-µSPE) and high-performance liquid chromatography (HPLC). The method showed wide linear ranges in the range of 0.3 to 300 ng mg-1 and low limits of detection (LODs) ranged from 0.1 to 0.2 ng mg-1 of hair.

A critical review of covalent organic frameworks-based sorbents in extraction methods.

Recently, covalent organic frameworks (COFs) as an important class of porous frameworks have been employed in analytical applications owing to their significant inherent properties such as a high specific surface area with modifiable pore size and a robust nature that leads to great stabilities. Also, COFs are flexible in design to deliberate changes in their physical or chemical properties by generating functionalized COFs or COF-based composites. Here, we summarize some important categories of COFs from the point of view of their design and synthetic strategies. Subsequently, the synergistic combination aspects of COFs with other materials such as different types of magnetic, metal/metal oxide nanoparticles, silica, carbon nanomaterials, polymers, polyoxometalates (POMs), metal-organic frameworks (MOFs), and COFs are reviewed. Finally, the recent applications of COFs as efficient sorbents in analytical sample preparation methods including solid-phase extraction (SPE), dispersive solid-phase extraction (dSPE), magnetic solid-phase extraction (MSPE), and solid-phase microextraction (SPME) will be surveyed with emphasis on important factors that lead to increase extraction efficiency. In addition, challenges and obstacles in these approaches are discussed with perspective highlights.

Lanthanoid-containing polyoxometalate nanocatalysts in the synthesis of bioactive isatin-based compounds.

Lanthanoid-containing polyoxometalates (Ln-POMs) have been developed as effective and robust catalysts due to their Lewis acid-base active sites including the oxygen-enriched surfaces of POM and the unique 4f. electron configuration of Ln. As an extension of our interest in Ln-POMs, a series of as-synthesized nanocatalysts K15[Ln(BW11O39)2] (Ln-B2W22, Ln = La, Ce, Nd, Sm, Gd, and Er) synthesized and fully characterized using different techniques. The Ln3+ ion with a big ionic radius was chosen as the Lewis acid center which is sandwiched by two mono-lacunary Keggin [BW11O39]9- units to form Ln-containing sandwiched type cluster. Consequently, the catalytic activity of nanocatalysts with different Ln was examined in the synthesis of bioactive isatin derivatives and compared under the same optimized reaction conditions in terms of yields of obtained products, indicating the superiority of the nano-Gd-B2W22 in the aforementioned simple one-pot reaction. The effects of different dosages of nanocatalyst, type of solvent, reaction time, and reaction temperature in this catalytic system were investigated and the best results were obtained in the presence of 10 mol% of nano-Gd-B2W22 in water for 12 min at the reflux condition.

Single-molecule magnets within polyoxometalate-based frameworks.

As an extension of our interest in polyoxometalates (POMs) and lanthanoids, we report the design and synthesis of two polyoxometalate-based frameworks under hydrothermal conditions; [Ho4(PDA)4(H2O)11][(SiO4)@W12O36]·8H2O (1) and [Tb4(PDA)4(H2O)12][(SiO4)@W12O36]·4H2O (2) (H2PDA = 1,10-phenanthroline-2,9-dicarboxylic acid). Both hybrids have been characterized by elemental analysis, Fourier transform infrared spectroscopy, thermogravimetric analysis, and powder/single-crystal X-ray diffraction. According to the structural analysis, 1 and 2 consist of 2D-cationic coordination polymers based on the respective lanthanoids and PDA2- as well as Keggin anions that reside in the interspaces between two adjacent layers as discrete counterions connected by extensive hydrogen bonding. Although the overall structures of 1 and 2 are composed of cationic and anionic layers, there are many differences in the cationic layers such as various coordination modes of PDA2-, different void shapes, and the existence of dinuclear Tb(III) units only in 2. Frameworks 1 and 2 were further characterized by dc and ac magnetic measurements and both exhibit slow relaxation of magnetization at low temperatures under an applied dc field. Their single-molecule magnet (SMM) properties are investigated, where weak field-induced SMM behaviour is observed at low temperatures in dynamic magnetic studies.

A redetermination of the structure and Hirshfeld surface analysis of poly[di-aquadi-µ-hydroxido-tetra-kis-(µ-nicotinato N-oxide)tricopper(II)].

The product obtained from the reaction of pyridine-2,3-di-carb-oxy-lic acid and hydrated copper(II) chloride in hot aqueous NaOH solution was determined by low temperature X-ray diffraction to be [Cu3(C6H4NO3)4(OH)2(H2O)2] n or [Cu3(µ-OH)2(µ-nicNO)4(H2O)2] n (nicNO is pyridine-3-carboxyl-ate N-oxide), a structure obtained from room temperature data and reported previously. The present determination is improved in quality and treatment of the H atoms. A Hirshfeld surface analysis of the inter-molecular inter-actions is presented.

Efficient dispersive micro solid-phase extraction of antidepressant drugs by a robust molybdenum-based coordination polymer.

A molybdenum-based coordination polymer {[Mo(PDA)(NO)(µ-O)MoO3]·1.42H2O·0.58C2H5OH}n (1) (PDA is 1,10-phenanthroline-2,9-dicarboxylate) was synthesized using solvothermal reaction conditions and characterized using a suite of analytical techniques. Single-crystal X-ray diffraction studies reveal a 1D chain structure, with close contacts expanding the structure into 3D including π-interactions and hydrogen bonding. The utility of 1 as a sorbent for dispersive micro solid-phase extraction (D-µSPE) of basic organic compounds such as antidepressants is supported by the presence of many functional groups on the surface of 1 (such as pendant carboxylates, Mo=O, Mo-NO, and CH groups) as well as extensive electrostatic interactions. Therefore, 1 can be a suitable choice as sorbent in the D-µSPE of antidepressant drugs from human plasma samples via appreciable adsorbate-adsorbent interactions. Determination of the extracted antidepressant drugs was conducted using high-performance liquid chromatography-ultraviolet (HPLC-UV), with calibration plots being linear in the concentration range 0.1-500 ng mL-1 for amitriptyline and nortriptyline, 0.2-500 ng mL-1 for imipramine, and 0.5-300 ng mL-1 for sertraline. The relative standard deviation (RSD) values were calculated for both intra-day and inter-day precision, and the RSD% values were in the range 3.9 to 5.2% and 4.6-5.4%, respectively. The limits of detection (LODs) was determined as 0.03-0.2 ng mL-1. Due to the good stability and reusability of the sorbent, the adsorption capacity had no obvious decrease after being used 20 times. Finally, the D-µSPE-HPLC-UV method was applied for the determination of antidepressant drugs in human plasma samples with recoveries of the analytes in the range 94.9 to 102%. The article describes the synthesis of a robust molybdenum-based coordination polymer, and its application as sorbent for dispersive micro solid-phase extraction of antidepressant drugs from human plasma samples.

Relationship between perceived social support and psychological hardiness with family communication patterns and quality of life of oncology patients.

AIM: The purpose of this study was to determine the relationship between PSS, PH, FCP and QoL of oncology patients. METHODS: In this descriptive-correlational study, 340 oncology patients were selected with convenience sampling method from the hospitals in Tehran 2018-2019. Data were collected using, "PSS," "PH," "FCP" and "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, EORTC QLQ-C30." Data were analysed using descriptive and inferential statistics using SPSS21 and Amos. RESULTS: The direct effect and the total effect of PSS and FCP on QoL were significant (p < .001), but their indirect effect was not significant (p > .05) and the effect of PH on QoL was not significant (p = .96). The Root Mean Squares of Error Approximations (RMSEA), Non-Normed Fit Index (NNFI), Comparative Fit Index (CFI) and Goodness of Fit Index (GFI) were estimated 0.07, 0.97, 0.98 and 0.91, respectively.

Coordination complexes of zinc and manganese based on pyridine-2,5-dicarboxylic acid N-oxide: DFT studies and antiproliferative activities consideration.

We report here the design, synthesis, and antiproliferative activity of three coordination complexes [Mn2(pydco)2(bpy)2(H2O)2]·2H2O (1), [Zn(bpy)(Hpydco)2] (2), and [Zn(bpy)Cl(Hpydco)]·2H2O (3) (H2pydco = pyridine-2,5-dicarboxylic acid N-oxide, bpy = 2,2'-bipyridine). Molecular structures of these complexes have been characterized by elemental analysis, Fourier transform infrared spectroscopy, thermogravimetric analysis, and powder and single-crystal X-ray diffraction. According to the structural analysis, 1-3 are discrete complexes containing N- and O-donor ligands (bpy and pydco2-) in which pydco2- can be coordinated to the metal centres via the N-oxide oxygen and one carboxylate oxygen to generate a six-membered chelate ring. Also, these structures benefit from extensive intermolecular interactions such as hydrogen bonds and π-interactions which are the major forces to make them more stable in the solid state. The energetic features of the π-stacking interactions observed in compounds 1-3 have been computed and compared to the H-bonds. The interactions in the solid state have been also studied using the independent gradient model approach (IGM plot). The IGM-δg approach uses a new descriptor (δg) that locally represents the difference between a virtual upper limit of the electron density gradient and the true electron density gradient. This newly developed IGM methodology automatically extracts the signature of interactions between two given fragments. Finally, the antiproliferative properties of these complexes were tested on several cancer cell lines by MTT assay and flow cytometry. Also, to compare the antiproliferative activities of these complexes with common chemotherapy drugs, the antiproliferative property of cisplatin was evaluated as a reference and positive control.

On the preferences of five-membered chelate rings in coordination chemistry: insights from the Cambridge Structural Database and theoretical calculations.

The purpose of this review is to give an overview of three important N-bidentate ligands: 1,10-phenanthroline (phen), 2,2'-bipyridine (bpy), and ethylenediamine (en). We have not attempted to be comprehensive because of the huge amount of activity being done in coordination chemistry using these ligands. Instead we present a full structural and geometrical study by using the Cambridge Structural Database (CSD) combined with theoretical calculations that allow us to parameterize their coordinating properties and ability to coordinate to transition and non-transition metals. More importantly, we illustrate that upon coordination and formation of the five-membered chelate ring, these ligands are able to adapt themselves to the requirements of the different metals by changing the MN distances and NMN angles. Therefore, a redefinition of the preferences of these ligands to metals with large ionic radii is needed. Finally, we will present some facts about the participation of these ligands in inorganic-organic hybrids (IOHs) based on Keggin polyoxometalates (POMs).

Validation of the Australian Midwifery Standards Assessment Tool (AMSAT): A tool to assess midwifery competence.

BACKGROUND: There is no current validated clinical assessment tool to measure the attainment of midwifery student competence in the midwifery practice setting. The lack of a valid assessment tool has led to a proliferation of tools and inconsistency in assessment of, and feedback on student learning. OBJECTIVE: This research aimed to develop and validate a tool to assess competence of midwifery students in practice-based settings. DESIGN: A mixed-methods approach was used and the study implemented in two phases. Phase one involved the development of the AMSAT tool with qualitative feedback from midwifery academics, midwife assessors of students, and midwifery students. In phase two the newly developed AMSAT tool was piloted across a range of midwifery practice settings and ANOVA was used to compare scores across year levels, with feedback being obtained from assessors. FINDINGS: Analysis of 150 AMSAT forms indicate the AMSAT as: reliable (Cronbach alpha greater than 0.9); valid-data extraction loaded predominantly onto one factor; and sensitivity scores indicating level of proficiency increased across the three years. Feedback evaluation forms (n=83) suggest acceptance of this tool for the purpose of both assessing and providing feedback on midwifery student's practice performance and competence. CONCLUSION: The AMSAT is a valid, reliable and acceptable midwifery assessment tool enables consistent assessment of midwifery student competence. This assists benchmarking across midwifery education programs.

Rosiglitazone Metabolism in Human Liver Microsomes Using a Substrate Depletion Method.

BACKGROUND: Elimination of rosiglitazone in humans is via hepatic metabolism. The existing studies suggest that CYP2C8 is the major enzyme responsible, with a minor contribution from CYP2C9; however, other studies suggest the involvement of additional cytochrome P450 enzymes and metabolic pathways. Thus a full picture of rosiglitazone metabolism is unclear. OBJECTIVE: This study aimed to improve the current understanding of potential drug-drug interactions and implications for therapy by evaluating the kinetics of rosiglitazone metabolism and examining the impact of specific inhibitors on its metabolism using the substrate depletion method. METHODS: In vitro oxidative metabolism of rosiglitazone in human liver microsomes obtained from five donors was determined over a 0.5-500 µM substrate range including the contribution of CYP2C8, CYP2C9, CYP3A4, CYP2E1, and CYP2D6. RESULTS: The maximum reaction velocity was 1.64 ± 0.98 nmol·mg-1·min-1. The CYP2C8 (69 ± 20%), CYP2C9 (42 ± 10%), CYP3A4 (52 ± 23%), and CEP2E1 (41 ± 13%) inhibitors all significantly inhibited rosiglitazone metabolism. CONCLUSION: The results suggest that other cytochrome P450 enzymes, including CYP2C9, CYP3A4, and CEP2E1, in addition to CYP28, also play an important role in the metabolism of rosiglitazone. This example demonstrates that understanding the complete metabolism of a drug is important when evaluating the potential for drug-drug interactions and will assist to improve the current therapeutic strategies.

Limited fetal metabolism of rosiglitazone: Elimination via the maternal compartment in the pregnant ewe.

Despite the fact that fetal drug exposure is common, the disposition of drugs in the fetus is poorly understood. This study aimed to investigate fetal placental and non-placental disposition of rosiglitazone in the pregnant ewe. Steady state was reached after day 5 of fetal infusion, and were ∼1.8 fold higher than maternal concentrations (P<0.001). The AUC for fetal rosiglitazone concentration throughout the infusion was inversely correlated with placental and fetal weight. Metabolic activity of the fetal liver microsomes were ∼25 fold lower than maternal microsomes (P<0.001). The findings suggest that trans-placental transfer is the major route through which rosiglitazone is cleared from the fetal compartment, while non-placental hepatic elimination makes only a minor contribution. This supports a limited capacity of the fetus for eliminating this class of drugs, and highlights the potential for drug toxicity when administering pharmacotherapy to the mother/fetus in human pregnancy.

Hepatoprotective activity of cinnamon ethanolic extract against CCI4-induced liver injury in rats.

The inner bark of cinnamon (Cinnamomum zeylanicum L.) is commonly used as a spice and has also been widely employed in the treatment and prevention of disease. The aim of the present study is to evaluate the protective effect of cinnamon bark extract against carbon tetrachloride (CCl4)-induced liver damage in male Wistar rats. Administration with cinnamon extracts (0.01, 0.05 and 0.1 g/kg) for 28 days significantly reduced the impact of CCl4 toxicity on the serum markers of liver damage, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase. In addition, treatment of cinnamon extract resulted in markedly increased the levels of superoxide dismutase and catalase enzymes in rats. The histopathological studies in the liver of rats also supported that cinnamon extract markedly reduced the toxicity of CCl4 and preserved the histoarchitecture of the liver tissue to near normal. Thus, the results suggest that cinnamon extract acts as a potent hepatoprotective agent against CCl4 induced hepatotoxicity in rats.

Simple HPLC method for determination of rosiglitazone in sheep plasma and amniotic fluid and its application in a pregnant sheep model.

This paper describes the development of a sensitive high performance liquid chromatography (HPLC) method for quantification of rosiglitazone in sheep plasma and amniotic fluid. Samples were prepared by liquid-liquid extraction using tert-butyl methyl ether, and rosiglitazone was quantitated by HPLC using a C18 column and fluorescence detector with an excitation wavelength of 247 nm and emission wavelength of 367 nm. The mobile phase consisted of ammonium acetate (10 mM, pH 5.2) and acetonitrile (56.5:43.5, v/v) with a flow rate of 1 ml/min. Ketoconazole was used as the internal standard (IS). The plasma calibration curve was linear over the range of 2.5-250 ng/ml (mean r2=0.9940±0.0024; n=6) with accuracy of 99.4-102.8% over the calibration range. The intra-day and inter-day coefficient of variation (%CV, percent coefficient of variation) were in the range of 0.01-8.68% in sheep plasma. Similar performance was achieved for amniotic fluid. The described method was successfully applied to quantitate rosiglitazone concentrations in the pregnant ewe and her fetus.

Preconditioning with acute and chronic lithium administration reduces ischemia/reperfusion injury mediated by cyclooxygenase not nitric oxide synthase pathway in isolated rat heart.

Lithium is widely used for the management of neuropsychiatric symptoms in bipolar disorders. A variety of hypotheses have been invoked to explain the mechanism of action of lithium. To determine if lithium exerts direct cardiac protection, in the present study perfused rat heart model was used. The mechanism of lithium-mediated cardioprotection was explored by combined use of lithium and nitro-L-arginine methyl ester (L-NAME, a non-selective nitric oxide synthase inhibitor) or indomethacin (a non-selective cyclooxygenase pathway inhibitor). Rat isolated hearts were used for Langendorff perfusion. Hearts were either non-preconditioned or preconditioned with acute lithium (3 mM) or chronic lithium (600 mg/l in tap water for 4 weeks, 0.265 +/- 0.023 mM in serum) before 30 min global ischemia followed by 90 min reperfusion. Within each of these protocols, hearts were divided into two groups; one group was exposed to L-NAME (0.1 mM) and another group was exposed to indomethacin (10 microM). Infarct size was measured by the triphenyltetrazolium chloride method. Left ventricular function was assessed by left ventricular developed pressure (LVDP), heart rate and coronary flow (CF). In our experiment acute and/or chronic administration of lithium before prolonged ischemia offered significant myoprotective effects in terms of infarct size reduction and improved cardiac function against ischemia/reperfusion injury. The effects of lithium pretreatment were prevented by the administration of indomethacin but not L-NAME. In conclusion, our results demonstrate that preconditioning with acute and/or chronic lithium administration improves recovery of the ventricular function and reduces infarct size via cyclooxygenase (COX) pathway in isolated rat heart.