Many-point boundary-value problem for some differential-operational equations

The existence and uniqueness of strong solution of many-point boundary-value problems for some differential-operational equations and its continuous dependence on the coefficients are investigated. The tool employed in our analysis is the method of an energy inequality.     

Calorimetric determination of enthalpy changes for the proton ionization of glycine, N,N-bis(2-hyroxyethyl)glycine (“bicine”) and N-tris(hydroxymethyl)methylglycine (“tricine”) in water-methanol mixtures

Enthalpies for the two proton ionizations of glycine, N,N-bis(2-hyroxyethyl)glycine (“bicine”) and N-tris(hydroxymethyl)methylglycine (“tricine”) were obtained in water-methanol mixtures with methanol mole fraction (X_m) from 0 to 0.360. With increasing methanol the ionization enthalpy for the first proton (ΔH₁) of glycine increased from 4.4 to 9.4 kJ mol⁻¹ with a minimum of 4.1 kJ mol⁻¹ at X_m = 0.059. The ionization enthalpy of the second proton (ΔH₂) for glycine decreased from 46.3 to 38.1 kJ mol⁻¹. ΔH₁ of bicine increased from 3.5 to 7.6 kJ mol⁻¹ at X_m = 0.273 before dropping to 4.1 kJ mol⁻¹ at X_m = 0.360. ΔH₂ of bicine increased from 24.9 to 29.4 kJ mol⁻¹. For tricine, ΔH₁ increased from 6.7 to 9.8 kJ mol⁻¹ at X_m = 0.194 then dropped to 7.4 kJ mol⁻¹ at X_m = 0.360. ΔH₂ for tricine first dropped from 30.8 to 28.5 kJ mol⁻¹ at X_m = 0.059 before increasing to 33.3 kJ mol⁻¹ at X_m = 0.273. The solvent composition was selected so as to include the region of maximum structure enhancement of water by methanol. The results were interpreted in terms of solvent-solvent and solvent-solute interactions.     

Sequential extraction for the speciation of some heavy metals in soils

The five step sequential extraction for speciation of copper and nickel originally designed for sediments has been applied to soil samples. The extractant solutions were: 1 mol/l ammonium acetate, 1 mol/l hydroxylammonium chloride in 25% acetic acid (1∶1), 0.1 mol/l hydrochlorid acid, 0.5 mol/l sodium hydroxide and 8 mol/l nitric acid. The residue was decomposed by HF and HNO₃. Using this procedure the metal fraction bound to the organic matter can be distinguished. The concentrations of analytes were determined in the soil extracts by FAAS and ETAAS. Accuracy was assessed by comparing the sum of the contents of copper and nickel in soil extracts with the total certified values of CRMs of soils. The overall recovery values for nickel was 84–105% and for copper 105–114%.     

Seleninate in place of phosphate: irreversible inhibition of protein tyrosine phosphatases

A homotyrosine based seleninic acid irreversibly inhibits protein tyrosine phosphatases by forming a covalent selenosulfide linkage with the active site cysteine sulfhydryl specifically. The details of the event are revealed by model synthetic studies and by kinetic, mass spectrometric, and crystallographic characterization.     

Delivery systems for some biologically active 1,2,4‐triazine derivatives: synthesis and release

Triazine‐loaded polymer microparticles composed of cross‐linked polymethylmethacrylate (PMMA) have been prepared. A series of PMMA cross‐linked polymers were prepared from methylmethacrylate (MMA) and divinylbenzene (DVB) by suspension polymerization using different percentages of solvents and cross‐linkers. Biologically active compounds including 4‐amino‐6‐substituted‐3‐thioxo‐3,4‐dihydro‐2H‐5‐oxo (or thioxo)‐1,2,4‐triazines (I–IV) were prepared and reacted with PMMA. Since optimization of the polymer delivery system is required to improve clinical applications, the effect of surface area, cross‐linker percentage on the loading, and release of triazines were studied. Alkaline conditions seem to favorably affect triazine release. Triazine hydrochlorides were ion exchanged with sodium montmorillonite (Na‐MMT). X‐ray diffraction (XRD) analysis confirms the intercalation of triazines between the layers of MMT. The presence of mineral domains with an average size of 33 nm was observed by transmission electron microscopy (TEM). The release of triazine compounds is more controllable in intercalated layered silicates. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis and evaluation of novel 4H-pyrazole and thiophene derivatives derived from chalcone as potential anti-proliferative agents,Pim-1 kinase inhibitors,and PAINS

The chalcone derivatives 3a-d reacted with either malononitrile or ethyl cyanoacetate in ethanol in the presence of catalytic amount of ammonium acetate in an oil bath at 120°C to give the Knowevenagel condensation products 5a-h . The latter compounds reacted with hydrazine hydrate and afforded the 4H-pyrazole derivatives 7a-h , respectively. The reaction of compounds 7a-h with ethyl cyanoacetate in dimethylformamide under refluxing condition afforded the cyanoacetamido derivatives 8a-h , respectively. When compounds 8a-h reacted with elemental sulfur and either of malononitrile or ethyl cyanoacetate in ethanol containing triethylamine, the thiophene derivatives 9a-h and 10a-h , respectively, were obtained. The structure of the newly synthesized compounds was established by the analytical and spectral data. All the newly synthesized compounds were evaluated against the six cancer cell lines: A549, HT-29, MKN-45, U87MG, and SMMC-7721 and H460. Compounds 3c , 5h , 7g , 7h , 8f , 9e , 9g , and 10g were selected to examine their Pim-1 kinase inhibition activity as these compounds showed high inhibition toward the c-Met kinase and the tested cancer cell lines. Furthermore, compounds 3b , 3c , 5g , 5h , 7f , 7g , 7h , 8e , 8f , 8g , 8h , 9e , 9f , 9g , 9h , 10g and 10h were selected to be tested for pan-assay interference compounds analysis (PAINS). Almost all the tested compounds showed zero PAINS alert and can be used as drug compounds in the future.     

Synthesis and Antimicrobial Activities of Some 6-Methyl-3-Thioxo-2,3-Dihydro-1,2,4-Triazine Derivatives

Abstract

4-Arylidene-imidazole derivatives (4a,b) were readily prepared by reacting 4-am- ino-6-methyl-3–thioxo-2,3–dihydro[1,2,4]triazin-5(4H)-one (1) with 4-arylidene-2-phenyl- 4H-oxazol-5-one (2). Reaction of 1 with some aromatic aldehydes in presence of triethylphosphite exclusively afforded the corresponding aminophosphonates 5a-c. Reaction of 1 with 3-phenyl-1H-quinazoline-2,4-dione (6a) and/or 3-phenyl-2-thioxo-2,3-dihydro- 1H-quinazolin-4-one (6b) gave 2-(6-methyl-5-oxo-3-thioxo-2,5-dihydro-3H-[1,2,4]triazin-4-ylimino)-3-phenyl-2,3-dihydro-1H-quinazolin-4-one (7). Moreover, on treating 1 with 2-phenylbenzo[d][1,3]thiazine-4-thione (8), 6-methyl-4-(2-phenyl-4-thioxo-4H-quinazolin-3-yl)-3-thioxo-3,4-dihydro-2H-[1,2,4]triazine-5-one (9) was obtained in 65% yield. Reaction of 1 with 4-sulfonylaminoacetic acid derivatives (10a,b) afforded the corresponding sulfonamides (11a,b), respectively. Acid hydrolysis of 11a afforded 7-aminomethyl-3-methyl[1,3,4]thiadiazole[2,3-c][1,2,4]triazin-4-one (12). 4-Amino-6-methyl-3-(morpholine-4-ylsulfanyl)-4H-[1,2,4]triazin-5-one (14) was prepared by reacting compound 1 with morpholine in presence of KI/I₂, while 3,3′-bis(4-amino-6-methyl-5-oxo-triazinyl)disulfide (16) was obtained by oxidation of 1 with lead tetraacetate. The antimicrobial activity of the products was evaluated against Gram-positive and Gram-negative bacteria as well as the fungus Candida albicans.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures, and tables.]     

Signal amplification in NbN superconducting resonators via stochastic resonance

We exploit nonlinearity in NbN superconducting stripline resonators, which originates from local thermal instability, for studying stochastic resonance. As the resonators are driven into instability, small amplitude modulation (AM) signals are amplified with the aid of injected white noise. Simulation results based on the equations of motion for the system yield a good agreement with the experimental data both in the frequency and time domains.     

Design,synthesis and characterization of tin‐based cancer chemotherapy drug entity: In vitro DNA binding,cleavage, induction of cancer cell apoptosis by triggering DNA damage‐mediated p53 phosphorylation and molecular docking

A new organotin complex derived from propyl gallate and 1,10‐phenanthroline was designed, synthesized and characterized using spectroscopic and elemental analytical methods. The underlying mechanisms of the anticancer action of the tin complex were further elucidated by evaluating its in vitro DNA interaction and the regulating signaling pathways. Our results showed that the tin complex could effectively activate DNA strand breaks in MCF‐7 cells in a dose‐dependent manner after cellular internalization. Phosphorylation of a DNA damage marker, histone H2A.X (Ser139), was thus upregulated in treated cells. Additionally, our results indicate that p53 is phosphorylated in response to DNA damage, and that this phosphorylation may be involved in the subsequent induction and activation of p53. In vitro DNA binding of the complex in Tris–HCl buffer was studied using various biophysical methods, revealing that the tin complex binds to DNA non‐covalently via electrostatic interaction. The higher K_b value of the complex suggested greater DNA binding propensity. Further, to evaluate the mode of action at the molecular level, interaction studies of the tin complex with nucleotide (5′‐GMP) were carried out. The complex exhibits DNA cleavage activity with supercoiled pBR322 in the presence of different activators. The complex cleaves DNA efficiently via oxidative cleavage pathway. Molecular docking studies were performed to understand the binding mode of the tin complex with DNA (PDB ID: 1BNA).     

A selective and direct synthesis of 2-bromo-4-alkylthiophenes: Convenient and straightforward approaches for the synthesis of head-to-tail (HT) and tail-to-tail (TT) dihexyl-2,2′-bithiophenes

A straightforward method for the synthesis of 2-bromo-4-alkylthiophenes was developed, and the desired products were obtained in the highest chemical yields (>90%) reported to date. 2-Bromo-4-alkylthiophenes were synthesized by regioselective lithiating of 3-alkylthiophenes with n-BuLi and quenching with bromine at −78 °C. Moreover, a simple and efficient protocol for the synthesis of dihexyl-2,2′-bithiophenes was developed by employing 2-bromo-4-hexylthiophene instead of the commonly used monomer, 2-bromo-3-hexylthiophene. Kumada and Suzuki cross-coupling reactions were conducted to synthesize the desired products as head-to-tail (HT) and tail-to-tail (TT) regioisomers in high yields and excellent selectivity.