Novel potentiometric copper (II) selective membrane sensors based on cyclic tetrapeptide derivatives as neutral ionophores

Two novel membrane sensors sensitive and reasonably selective for Cu²⁺ ions are described. These are based on the use of newly synthesized cyclic tetrapeptide derivatives as neutral ionophores and sodium tetraphenylborate (NaTPB) as an anionic excluder in plasticized PVC membranes. The sensors exhibit fast and stable near-Nernstian response over the concentration range 1.0 × 10⁻⁶ mol l⁻¹ to 1.0 × 10⁻² mol l⁻¹ Cu²⁺ with a cationic slope of 30.2-25.9 mV per decade at pH 4.5-7 with a lower detection limit of 0.05-0.13 μg ml⁻¹. Effects of plasticizers, lipophilic salts and various foreign common ions are tested. The sensors display long life-span, long term stability, high reproducibility, and short response time. Selectivity of both sensors is significantly high for Cu²⁺ over Fe³⁺, Al³⁺, Zn²⁺, Cd²⁺, Hg²⁺, Ni²⁺, Co²⁺, Mn²⁺, alkaline earth and alkali metal ions. The sensors are used for direct measurement of copper content in different rocks and industrial wastewater samples from electroplating factories. The results agree fairly well with data obtained using atomic absorption spectrometry.     

Synthesis and antioxidant screening of new 2-cyano-3-(1,3-diphenyl-1H-pyrazol-4-yl)acryloyl amide derivatives and some pyrazole-based heterocycles

Abstract

The high functionality compound namely 2-cyano-3-(1,3-diphenyl-1H-pyrazol-4-yl)acryloyl chloride (1) was utilized as a building block synthon via reactions with some nitrogen and sulfur nucleophilic reagents. The present work was planned to study the effect of 2-cyano group on the reactivity and stability of C₂–C₃ double bond toward different strong-to-weak nucleophiles, in addition to its facility of nucleophilic addition at C₂–C₃ double bond to construct new heterocyclic derivatives. The proclivity toward some mono-, 1,2-, 1,3-, 1,4-, and 1,5-binucleophiles was investigated. The reaction with 2-cyanoacetohydrazide was mainly dependent on the reaction conditions. Some new heterocycles integrated with pyrazole scaffold were successfully synthesized, such as benzoxazinone, indoline, isoindoline, pyrazolone, chromene, and pyrimidopyrimidine derivatives. Some of the newly synthesized compounds were screened for their antioxidant activity using ABTS method, and the results revealed that some compounds exhibited promising inhibitory antioxidant activity.     

Fuzzy job shop scheduling with lot-sizing

This paper deals with a problem of determining lot-sizes of jobs in a real-world job shop-scheduling in the presence of uncertainty. The main issue discussed in this paper is lot-sizing of jobs. A fuzzy rule-based system is developed which determines the size of lots using the following premise variables: size of the job, the static slack of the job, workload on the shop floor, and the priority of the job. Both premise and conclusion variables are modelled as linguistic variables represented by using fuzzy sets (apart from the priority of the job which is a crisp value). The determined lots’ sizes are input to a fuzzy multi-objective genetic algorithm for job shop scheduling. Imprecise jobs’ processing times and due dates are modelled by using fuzzy sets. The objectives that are used to measure the quality of the generated schedules are average weighted tardiness of jobs, the number of tardy jobs, the total setup time, the total idle time of machines and the total flow time of jobs. The developed algorithm is analysed on real-world data obtained from a printing company.     

Design,Synthesis and Anticancer Evaluation of Substituted Cinnamic Acid Bearing 2-Quinolone Hybrid Derivatives

A new series of hybrid molecules containing cinnamic acid and 2-quinolinone derivatives were designed and synthesized. Their structures were confirmed by ¹H-NMR, ¹³C-NMR and mass analyses. All the synthesized hybrid molecules were assessed for their in vitro antiproliferative activity against more than one cancer cell lines. Compound 3-(3,5-dibromo-7,8-dihydroxy-4-methyl-2-oxoquinolin-1(2H)-ylamino)-3-phenylacrylic acid (5a) with IC₅₀ = 1.89 μM against HCT-116 was proved to the most potent compound in this study, as compared to standard drug staurosporin. DNA flow cytometry assay of compound 5a revealed G2/M phase arrest and pre-G1 apoptosis. Annexin V-FITC showed that the percentage of early and late apoptosis was increased. The results of topoisomerase enzyme inhibition activity showed that the hybrid molecule 5a displays potent inhibitory activity compared with control.     

Molecular Docking Study of Newly Synthesized Thiopyrimidines as Antimicrobial Agents Targeting DNA Gyrase Enzyme

A new series of thiopyrimidine‐5‐carbonitrile derivatives were synthesized and the chemical identity of them was established on the basis of spectral methods. The antimicrobial properties of all derivatives were investigated against Gram‐positive and Gram‐negative bacteria as well as fungal strains. The results of the antimicrobial screening showed that compounds 4 , 11 , and 12 have a higher and broad spectrum efficacy against all the tested organisms in comparison with the reference drugs. Interestingly, the most active compounds 4 and 12 showed good binding assay results with Escherichia coli DNA gyrase comparable to that of the reference, methotrexate. Furthermore, a molecular docking study of these compounds was carried out to investigate their binding pattern with the target, DNA gyrase.     

Resolution of chiral phosphate, phosphonate, and phosphinate esters by an enantioselective enzyme library

An array of 16 enantiomeric pairs of chiral phosphate, phosphonate, and phosphinate esters was used to establish the breadth of the stereoselective discrimination inherent within the bacterial phosphotriesterase and 15 mutant enzymes. For each substrate, the leaving group was 4-hydroxyacetophenone while the other two groups attached to the phosphorus core consisted of an asymmetric mixture of methyl, methoxy, ethyl, ethoxy, isopropoxy, phenyl, phenoxy, cyclohexyl, and cyclohexoxy substituents. For the wild-type enzyme, the relative rates of hydrolysis for the two enantiomers ranged from 3 to 5.4 x 10(5). Various combinations of site-specific mutations within the active site were used to create modified enzymes with alterations in their enantioselective properties. For the single-site mutant enzyme, G60A, the stereoselectivity is enhanced relative to that of the wild-type enzyme by 1-3 orders of magnitude. Additional mutants were obtained where the stereoselectivity is inverted relative to the wild-type enzyme for 13 of the 16 pairs of enantiomers tested for this investigation. The most dramatic example was obtained for the hydrolysis of 4-acetylphenyl methyl phenyl phosphate. The G60A mutant preferentially hydrolyzes the SP-enantiomer by a factor of 3.7 x 10(5). The I106G/F132G/H257Y mutant preferentially hydrolyzes the RP-enantiomer by a factor of 9.7 x 10(2). This represents an enantioselective discrimination of 3.6 x 10(8) between these two mutants, with a total of only four amino acid changes. The rate differential between the two enantiomers for any given mutant enzyme is postulated to be governed by the degree of nonproductive binding within the enzyme active site and stabilization of the transition state. This hypothesis is supported by computational docking of the high-energy, pentavalent form of the substrates to modeled structures of the mutant enzyme; the energies of the docked transition-state analogues qualitatively capture the enantiomeric preferences of the various mutants for the different substrates. These results demonstrate that the catalytic properties of the wild-type phosphotriesterase can be exploited for the kinetic resolution of a wide range of phosphate, phosphonate, and phosphinate esters and that the active site of this enzyme is remarkably amenable to structural perturbations via amino acid substitution.     

Partially Mixing and Locally Rank 1 Smooth Transformations and Flows on the Torus Td, d >= 3

The paper gives the first examples of C measure preserving flowsand diffeomorphisms on the torus that are partially mixing andhave a simple spectrum.     

Poly(butyl methacrylate)-grafted alginate/Fe3O4 nanocomposite: Synthesis and its application for removal of dyes

This study involved the utilization of a free radical-graft copolymerization reaction for the development of a novel adsorbent, namely, poly(butyl methacrylate)-grafted alginate/Fe₃O₄ nanocomposite (PBMA-gft-Alg/Fe₃O₄). Transmission electron microscopy, scanning electron microscopy, energy-dispersive X-ray analysis, X-ray diffraction patterns analysis, and Fourier transform infrared spectroscopy (FT-IR) were carried out for the characterization of Fe₃O₄ NPs and PBMA-gft-Alg/Fe₃O₄ nanocomposites. The capability of nanocomposites and nanoparticles to adsorb dyes such as MG and MB, resulting in their removal from aqueous media, was evaluated under different conditions such as pH, temperature, contact time, and dose of adsorbent. Optimum parameters for adsorption of dyes were found to be pH of 10, 50°C, contact time of 180 min, and 0.2 g of adsorbent. Efficiency of the PBMA-gft-Alg/Fe₃O₄ nanocomposite was found to be significantly greater than that of Fe₃O₄ NPs for eliminating the desired dye. Langmuir, Freundlich, Sips, and Temkin models were used for testing the experimental data. Freundlich model was the one that best described the adsorption.     

Synthesis and in vitro evaluation of novel tetralin-pyrazolo[3,4-b]pyridine hybrids as potential anticancer agents

New hybrids of tetralin-pyrazolo[3,4-b]pyridine were synthesized in good yields. The structures of newly synthesized compounds were confirmed by IR, NMR, MS, and elemental analyses. Some of the new compounds were in vitro evaluated as antiproliferative candidates against two human cancer cell lines (HCT116 and MCF-7). Most of the examined derivatives showed promising anticancer activity.