Synthesis of some azeto[2,1-a]isoquinolin-2-ones

Some azeto[2,1-a]isoquinolin-2-ones were synthesized from 2-(3,4-dimethoxyphenyl)ethylamine in three steps in good yield.     

Ionizing radiation induces blockade of c-Jun N-terminal kinase-dependent cell death pathway in a manner correlated with p21(Cip/WAF1) induction in primary cultured normal human fibroblasts

During radiotherapy of cancer, neighboring normal cells may receive sub-lethal doses of radiation. To investigate whether such low levels of radiation modulate normal cell responses to death stimuli, primary cultured human fibroblasts were exposed to various doses of gamma-rays. Analysis of cell viability using an exclusion dye propidium iodide revealed that the irradiation up to 10 Gy killed the fibroblasts only to a minimal extent. In contrast, the cells efficiently lost their viability when exposed to 0.5-0.65 mM H(2)O(2). This type of cell death was accompanied by JNK activation, and was reversed by the use of a JNK-specific inhibitor SP600125. Interestingly, H(2)O(2) failed to kill the fibroblasts when these cells were pre-irradiated, 24 h before H(2)O(2) treatment, with 0.25-0.5 Gy of gamma-rays. These cytoprotective doses of gamma-rays did not enhance cellular capacity to degrade H(2)O(2), but elevated cellular levels of p21(Cip/WAF1), a p53 target that can suppress H(2)O(2)-induced cell death by blocking JNK activation. Consistently, H(2)O(2)-induced JNK activation was dramatically suppressed in the pre-irradiated cells. The overall data suggests that ionizing radiation can impart normal fibroblasts with a survival advantage against oxidative stress by blocking the process leading to JNK activation.     

Pt‐Nanoparticle Incorporated Carbon Paste Electrode for the Determination of Cu(II) Ion by Anodic Stripping Voltammetry

Pt‐nanoparticles were synthesized and introduced into a carbon paste electrode (CPE), and the resulting modified electrode was applied to the anodic stripping voltammetry of copper(II) ions. The synthesized Pt‐nanoparticles were characterized by cyclic voltammetry, scanning electron microscopy and X‐ray photoelectron spectroscopy techniques to confirm the purity and the size of the prepared Pt‐nanoparticles (ca. 20 nm). This incorporated material seems to act as catalysts with preconcentration sites for copper(II) species that enhances the sensitivity of Cu(II) ions to Cu(I) species at a deposition potential of ?0.6 V in an aqueous solution. The experimental conditions, such as, the electrode composition, pH of the solution, pre‐concentration time, were optimized for the determination of Cu(II) ion using as‐prepared electrode. The sensitivity changes on the different binder materials and the presence of surfactants in the test solution. The interference effect of the coexisted metals were also investigated. In the presence of surfactants, especially TritonX‐100, the Cu(II) detection limit was lowered to 3.9×10^?9 M. However, the Pt‐nanoparticle modified CPE begins to degrade when the period of deposition exceeds to 10 min. Linear response for copper(II) was found in the concentration range between 3.9×10^?8 M and 1.6×10^?6 M, with an estimated detection limit of 1.6×10^?8 M (1.0 ppb) and relative standard deviation was 4.2% (n=5).     

High-Throughput Analysis of Sofalcone in Human Plasma by Use of Automated 96-Well Protein Precipitation and LC-MS-MS

A sensitive and selective method for the determination of sofalcone in human plasma was established by use of protein precipitation and liquid chromatography-tandem mass spectrometry. Plasma samples were transferred into 96-well plate using an automated sample handling system and spiked with 10 L of 2 g mL^–1 internal standard solution (d₃-sofalcone). 0.5 mL of acetonitrile was added to the 96-well plate and the plasma samples were then vortexed for 30 sec. After centrifugation, the supernatant was transferred into another 96-well plate and completely evaporated at 40 °C under a stream of nitrogen. The dry residue was reconstituted with mobile phase. All sample transfer and protein precipitation was automated through the application of both the PerkinElmer MultiPROBE II HT and TOMTEC Quadra 96 workstation. The limit of quantitation of sofalcone was 2 ng mL^–1 using a sample volume of 0.2 mL for the analysis. The reproducibility of the method was evaluated by analyzing five samples at nine quality control (QC) levels over the nominal concentration range from 2 ng mL^–1 to 1000 ng mL^–1. Validation of the method showed that the assay has good precision and accuracy. Sofalcone and internal standard produced a protonated precursor ion ([M+H]⁺) at m/z 451 and 454, and both gave a corresponding product ion at m/z 315. The high sample throughput of the method has been successfully applied to a pharmacokinetic study of sofalcone in human plasma.     

High levels of soluble herpes virus entry mediator in sera of patients with allergic and autoimmune diseases

Herpes virus entry mediator (HVEM) is a newly discovered member of the tumor necrosis factor receptor (TNFR) superfamily that has a role in herpes simplex virus entry, in T cell activation and in tumor immunity. We generated mAb against HVEM and detected soluble HVEM (SHVEM) in the sera of patients with various autoimmune diseases. HVEM was constitutively expressed on CD4(+) and CD8(+) T cells, CD19(+) B cells, CD14(+) monocytes, neutrophils and dendritic cells. In three-way MLR, mAb 122 and 139 were agonists and mAb 108 had blocking activity. An ELISA was developed to detect sHVEM in patient sera. sHVEM levels were elevated in sera of patients with allergic asthma, atopic dermatitis and rheumatoid arthritis. The mAbs discussed here may be useful for studies of the role of HVEM in immune responses. Detection of soluble HVEM might have diagnostic and prognostic value in certain immunological disorders.     

Synthesis, characterization, and dioxygen reactivity of tetracarboxylate-bridged Diiron(II) complexes with coordinated substrates

The synthesis and characterization of [Fe(2)(micro-O(2)CAr(Tol))(4)L(2)] complexes, where L is benzylamine or 4-methoxybenzylamine (BA(p)()(-)(OMe)), are described. The reaction of the latter diiron(II) complex with dioxygen at -78 degrees C affords a metastable mixed-valent Fe(II)Fe(III) green intermediate. When O(2) is introduced at ambient temperature, N-dealkyation occurs to yield anisaldehyde, eliminating N-oxidation as a viable pathway for the reaction. Use of [Fe(2)(micro-O(2)CAr(T)(omicron)(l))(4)(alpha-d(1)-BA(p)()(-)(OMe))(2)] allowed a deuterium kinetic isotope of approximately 3 to be determined.     

Selective extraction of benzoic acid from landfill leachate by solid-phase extraction and ion-exchange chromatography

In this work a simple method was described for selective extraction of benzoic acid from landfill leachate samples. The samples were submitted to solid-phase extraction (SPE) with XAD-4 resin as the stationary phase and ion-exchange chromatography (IEC) using the ion-exchange resin Amberlyst A-27. The instrumental analysis was performed by gas chromatography with mass spectrometric detection (GC-MSD). Benzoic acid was isolated, identified and quantified. The extraction process is rapid, simple and of low cost. It was also environmental friendly, that is, it was used a minimum amounts of hazardous organic solvents and produced also minimum quantities of residues.     

Kinetics and mechanism of benzylamine additions to ethyl alpha-acetyl-beta-phenylacrylates in acetonitrile

Kinetic studies of the addition of benzylamines to a noncyclic dicarbonyl group activated olefin, ethyl alpha-acetyl-beta-phenylacrylate (EAP), in acetonitrile at 25.0 degrees C are reported. The rates are lower than those for the cyclic dicarbonyl group activated olefins. The addition occurs in a single step with concurrent formation of the Calpha-N and Cbeta-H bonds through a four-center hydrogen bonded transition state.The kinetic isotope effects (kH/kD > 1.0) measured with deuterated benzylamines (XC6H4CH2ND2) increase with a stronger electron acceptor substituent (deltasigmaX > 0) which is the same trend as those found for other dicarbonyl group activated series (1-4), but is in contrast to those for other (noncarbonyl) group activated series (5-9). For the dicarbonyl series, the reactivity-selectivity principle (RSP) holds, but for others the anti-RSP applies. These are interpreted to indicate an insignificant imbalance for the former, but substantial lag in the resonance delocalization in the transition state for the latter series.     

Stereodivergent and regioselective synthesis of 3,4-cis- and 3,4-trans-pyrrolidinediols from alpha-amino acids

[reaction: see text] Highly stereodivergent Woodward-Prevost reaction applied to iodoacetates derived from homochiral alpha-amino acids afforded enantiopure 3,4-cis- and 3,4-trans-pyrrolidinediol derivatives, with control over the protecting group, allowing for differential protection.     

Self-assemblies of new rigid angular ligands and metal centers toward the rational construction and modification of novel coordination polymer networks

Self-assemblies of rigid angular ligands with 120 degrees molecular angle and metal centers have been investigated with the aim of achieving the rational construction and modification of coordination polymer structures. The reactions of Co(NCS)(2) with 1,3-bis(trans-4-styrylpyridyl)benzene (L(1)()), 2,6-bis(trans-4-styrylpyridyl)pyridine (L(2)()), 1,3-bis(trans-4-styrylpyrimidyl)benzene (L(3)()), and 1,3-bis(trans-4-styrylquinoly)benzene (L(4)()) afford complexes [Co(L(1)())(2)(NCS)(2)]( infinity ) (1), [Co(L(2)())(2)(NCS)(2)]( infinity ) (2), Co(L(3)())(2)(NCS)(2)(CH(3)OH)(2) (3), and [Co(L(4)())(NCS)(2)]( infinity ) (4), respectively. The resulting complexes exhibit open framework, stairlike hydrogen-bonded chain and single-stranded helical coil structures, which are controlled by the variation of the geometry around the coordination site in ligands. Moreover, the coordination of L(1)() and L(2)() to Mn(hfac)(2) (hfac = 1,1,1,5,5,5-hexafluoroacetylacetonate) yields single-stranded helical coordination polymers of [Mn(L(1)())(hfac)(2)]( infinity ) (5) and [Mn(L(2)())(hfac)(2)]( infinity ) (6), respectively.