Synthesis and evaluation of stereopure α-trifluoromethyl-malic hydroxamates as inhibitors of matrix metalloproteinases

The total synthesis of trifluoromethyl (Tfm) analogs of known nanomolar matrix metalloproteinases (MMPs) inhibitors has been performed. The synthetic protocol is based on a moderately stereoselective aldol reaction of trifluoropyruvate with an N-acyl-oxazolidin-2-thione for the construction of the core α-Tfm-malic unit. Both the diastereomeric forms of the target α-Tfm-malic hydroxamates showed micromolar inhibitory potency toward MMP-2 and 9, with a substantial drop with respect to the parent unfluorinated compounds.     

Development of a new fluorimetric bulk optode membrane based on 2,5-thiophenylbis(5-tert-butyl-1,3-benzexazole) for nickel(II) ions

A highly sensitive and selective fluorimetric optode membrane for the determination of ultra trace amounts of Ni²⁺ ions was prepared. The plasticized PVC-membrane incorporating potassium tetrakis(p-chlorophenyl)borate (KTpClPB) and 2,5-thiophenylbis(5-tert-butyl-1,3-benzexazole) (TTBB), as a highly fluorescent chromoionophore, displays a calibration response for Ni²⁺ ions over a wide concentration range of 1.0×10⁻³ to 1.0×10⁻⁸ M. It has a relatively fast response of <40 s. In addition to high stability and reproducibility, and relatively long working lifetime, the sensor possesses good selectivity for nickel ions over several common diverse ions. The fluorescence signal of the optode membrane can be easily recovered by immersion in EDTA solution. The optode was applied successfully to the determination of traces of Ni²⁺ ion in edible oil and a wastewater sample from nickel electroplating industries.     

Potential Mechanisms of Photodynamic Inactivation of Virus by Methylene BlueI. RNA–Protein Crosslinks and Other Oxidative Lesions in Qβ Bacteriophage

A spectrum of oxidative lesions was observed in a bacteriophage-based model system that is very sensitive to the photodynamic activity of selected dyes. When suspensions of the intact bacteriophage Qβ were exposed to methylene blue plus light (MB+L), inactivating events, or "hits" occurred that were oxygen-dependent and that were associated with the formation of several specific lesions: (1) carbonyl moieties on proteins, (2) 8-oxo-7,8-dihydroguanine (8-oxoGua), and (3) single-strand breaks (ssb) in the RNA genome and (4) RNA-protein crosslinks. Formation of carbonyl groups associated with protein in the Qβ phage preparation correlated positively with photoinactivation of the phage with increasing doses of either of the sensitizers MB or rose bengal. Strand breaks in the Qβ genomic RNA were observable at high MB concentrations but appeared not to be significant at the lower concentrations of MB, as full-length Qβ RNA was observable well beyond the 99% inactivation point in MB dosage. It was shown that the number of 8-oxoGua lesions were unlikely to be sufficient to account for the number of lethal events. Following exposure to MB+L, crosslink formation between Qβ RNA and protein was observed by virtue of the location of RNA at the interface of phenol-aqueous extractions of phage suspensions. A significant increase over background of RNA-protein complexes (including full-length Qβ RNA) was observed at the lowest concentration of MB tested (0.5 μ M ), which corresponded roughly to an average of 2 lethal hits per phage or approximately 13% survival compared to the zero MB control (100% survival). Due to its close correlation with Qβ inactivation and its expected lethality, RNA-protein crosslink formation may be important as an inactivating lesion in bacteriophage Qβ following MB+L exposure.     

A Facile Room Temperature Synthesis of Zinc Oxide Nanostructure and Its Influence on the Flame Retardancy of Poly Vinyl Alcohol

In this work, poly vinyl alcohol–ZnO nanocomposites were synthesized via two different in situ and ex-situ methods. In ex-situ, at first zinc oxide nanostructures were synthesized by one-step precipitation reaction between zinc acetate and sodium hydroxide. The effect of different surfactants such as poly vinyl pyrrolidone, poly vinyl alcohol and poly ethylene glycol on the morphology of ZnO nanostructures was investigated. Nanostructures were characterized by X-ray diffraction, scanning electron microscopy. The influence of ZnO nanostructures on the flame retardancy of the poly vinyl alcohol matrix was studied using underwriter laboratories UL-94 analysis.     

Synthesis and cytotoxicity evaluation of diastereoisomers and N-terminal analogues of tubulysin-U

Tubulysins are potent anti-mitotic natural compounds and a scalable and efficient synthetic route for generation of its analogues has been developed and extended to the synthesis of diastereoisomers and N-terminal analogues of tubulysin-U. Structure–activity-relationship studies on these synthetic analogues reaffirmed the significance of native stereochemistry of tubulysins for optimal biological activity and cytotoxicity. However, while modification of Tup stereochemistry has only minor effect on the tubulysins cytotoxicity, Tuv stereochemistry is critically important and modification of either Tuv stereocentre produced a dramatic drop in cytotoxicity.     

Analysis of tamoxifen and its main metabolites in plasma samples of breast cancer survivor female athletes: Multivariate and chemometric optimization

A sensitive method based on liquid chromatography combined with a diode array detector was developed and validated to simultaneously determine tamoxifen, and its active metabolites N-desmethyltamoxifen, 4-hydroxytamoxifen, and endoxifen in human plasma samples. The green and sustainable vortex-assisted dispersive liquid-phase microextraction technique based on the natural hydrophobic deep eutectic solvent was used for the extraction and preconcentration of the analytes. Chemometrics and multivariate analysis were used to optimize the independent variables including the type and volume of deep eutectic solvent, extraction time, and ionic strength. Under optimal conditions, calibration curves were linear in a suitable range with the lower limits of quantification (0.8–10.0 μg/L), which covered the relevant concentrations of the analytes in plasma samples for a clinical study. Intra- and interday precision evaluated at three concentrations for the analytes were lower than 8.2 and 12.1%, respectively. Accuracy was in the range of 94.9–104.7%. The applicability of the developed method on human plasma samples illustrated the range 45.1–72.8, 98.4–128.3, 0.9–1.2, and 2.7–6.1 μg/L for tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen, and endoxifen, respectively. The validated method can be effective for the pharmacokinetics, pharmacodynamics, and therapeutic drug monitoring studies of tamoxifen and its main metabolites in biological fluids.     

Highly functionalized pyrazolines from symmetric and asymmetric 1,2-disulfonylhydrazines: a combination of experimental and DFT perspectives

Chemistry of Heterocyclic Compounds - In this work, new pyrazole derivatives were prepared by one-pot three-component reaction emloying symmetric and asymmetric 1,2-disulfonyl-hydrazines,...     

Artificial intelligence–based models for the qualitative and quantitative prediction of a phytochemical compound using HPLC method

Isoquercitrin is a flavonoid chemical compound that can be extracted from different plant species such as Mangifera indica (mango), Rheum nobile , Annona squamosal , Camellia sinensis (tea), and coriander ( Coriandrum sativum L.). It possesses various biological activities such as the prevention of thromboembolism and has anticancer, antiinflammatory, and antifatigue activities. Therefore, there is a critical need to elucidate and predict the qualitative and quantitative properties of this phytochemical compound using the high performance liquid chromatography (HPLC) technique. In this paper, three different nonlinear models including artificial neural network (ANN), adaptive neuro-fuzzy inference system (ANFIS), and support vector machine (SVM),in addition to a classical linear model [multilinear regression analysis (MLR)], were used for the prediction of the retention time (tR) and peak area (PA) for isoquercitrin using HPLC. The simulation uses concentration of the standard, composition of the mobile phases (MP-A and MP-B), and pH as the corresponding input variables. The performance efficiency of the models was evaluated using relative mean square error (RMSE), mean square error (MSE), determination coefficient (DC), and correlation coefficient (CC). The obtained results demonstrated that all four models are capable of predicting the qualitative and quantitative properties of the bioactive compound. A predictive comparison of the models showed that M3 had the highest prediction accuracy among the three models. Further evaluation of the results showed that ANFIS–M3 outperformed the other models and serves as the best model for the prediction of PA. On the other hand, ANN–M3proved its merit and emerged as the best model for tR simulation. The overall predictive accuracy of the best models showed them to be reliable tools for both qualitative and quantitative determination.     

A comparison on efficiency of virgin and sulfurized agro-based adsorbents for mercury removal from aqueous systems

Mercury adsorption by sulfur impregnated adsorbents seems to be one of the most efficient ways for removal of this toxic metal ion from wastewater and atmosphere. The aim of this work was to develop a method for preparation of low-cost sulfurized adsorbent from agricultural wastes; this approach combines two stages of (i) chemical activation with phosphoric acid and (ii) impregnation with powdered sulfur, in one step only. The physico-chemical properties of sulfurized adsorbent (AC-S) were determined with BET, FT-IR, Eschka method and pH_PZC measurements, and compared with those of the virgin sample (AC). It was found that sulfurization according to this method can introduce about 8 wt.% sulfur into the structure of adsorbent, in the forms of C–S, S–H, S–S and S=O functional groups. Although during the sulfur introduction processes, a decrease in surface area and micropore volume of the sulfurized adsorbent is to be expected, not only such decrease did not occur in this work, but a large increase in microporosity was seen. Thereupon, both the sulfur functionalities and extended microporosity of AC-S lead to higher capability of this sample for mercury adsorption rather than AC. Finally, the kinetics and equilibrium of mercury adsorption from aqueous solutions were studied for AC and AC-S.     

Two‐dimensional modeling for stability analysis of two‐phase stratified flow

The effect of wavelength and relative velocity on the disturbed interface of two‐phase stratified regime is modeled and discussed. To analyze the stability, a small perturbation is imposed on the interface. Growth or decline of the disturbed wave, relative velocity, and surface tension with respect to time will be discussed numerically. Newly developed scheme applied to a two‐dimensional flow field and the governing Navier–Stokes equations in laminar regime are solved. Finite volume method together with non‐staggered curvilinear grid is a very effective approach to capture interface shape with time. Because of the interface shape, for any time advancement, a new grid is performed separately on each stratified field, liquid, and gas regime. The results are compared with the analytical characteristics method and one‐dimensional modeling. This comparison shows that solving the momentum equation including viscosity term leads to physically more realistic results. In addition, the newly developed method is capable of predicting two‐phase stratified flow behavior more precisely than one‐dimensional modeling. It was perceived that the surface tension has an inevitable role in dissipation of interface instability and convergence of the two‐phase flow model. Copyright © 2009 John Wiley & Sons, Ltd.