Reactions of 2,3-bishydroxyimino-1,2,3,4-tetrahydro-quinoxalines and 2,3-bishydroxyimino-2,3-dihydro-4H-1,4-benzoxazines with ethyl chloroformate

Bishydroxyiminoquinoxalines 3a-b react with ethyl chloroformate 4 to afford the furazano[3,4-b]quinoxalines 5a-b . Bishydroxyiminobenzoxazines 6a-c on treatment with 4 are converted into the fused oxadiazolones 7a-c and 8a-c along with the bisethoxycarbonyloxyimino-derivatives 9a-c . From the reactions of 4 with the oxanilide dioximes 12a-c compounds 13a-c and 14a-b are obtained.     

Synthesis,Bioactivity, Pharmacokinetic and Biomimetic Properties of Multi-Substituted Coumarin Derivatives

A series of novel multi-substituted coumarin derivatives were synthesized, spectroscopically characterized, and evaluated for their antioxidant activity, soybean lipoxygenase (LOX) inhibitory ability, their influence on cell viability in immortalized human keratinocytes (HaCaT), and cytotoxicity in adenocarcinomic human alveolar basal epithelial cells (A549) and human melanoma (A375) cells, in vitro. Coumarin analogues 4a–4f, bearing a hydroxyl group at position 5 of the coumarin scaffold and halogen substituents at the 3-phenyl ring, were the most promising ABTS^•+ scavengers. 6,8-Dibromo-3-(4-hydroxyphenyl)-4-methyl-chromen-2-one (4k) and 6-bromo-3-(4,5-diacetyloxyphenyl)-4-methyl-chromen-2-one (3m) exhibited significant lipid peroxidation inhibitory activity (IC₅₀ 36.9 and 37.1 μM). In the DCF-DA assay, the 4′-fluoro-substituted compound 3f (100%), and the 6-bromo substituted compounds 3i (80.9%) and 4i (100%) presented the highest activity. The 3′-fluoro-substituted coumarins 3e and 4e, along with 3-(4-acetyloxyphenyl)-6,8-dibromo-4-methyl-chromen-2-one (3k), were the most potent lipoxygenase (LOX) inhibitors (IC₅₀ 11.4, 4.1, and 8.7 μM, respectively) while displaying remarkable hydroxyl radical scavenging ability, 85.2%, 100%, and 92.9%, respectively. In silico docking studies of compounds 4e and 3k, revealed that they present allosteric interactions with the enzyme. The majority of the analogues (100 μΜ) did not affect the cell viability of HaCaT cells, though several compounds presented over 60% cytotoxicity in A549 or A375 cells. Finally, the human oral absorption (%HOA) and plasma protein binding (%PPB) properties of the synthesized coumarins were also estimated using biomimetic chromatography, and all compounds presented high %HOA (>99%) and %PPB (60–97%) values.     

Third-order nonlinear optical properties of thin sputtered gold films

Au films of thickness ranging between 5 and 52 nm were prepared by sputtering on quartz substrates and their third-order nonlinear optical response was investigated by Optical Kerr effect (OKE) and Z-scan techniques using 532 nm, 35 ps laser pulses. All prepared films were characterized by XRD, AFM and UV-VIS-NIR spectrophotometry while their third-order susceptibility χ⁽³⁾ was measured and found to be of the order of 10⁻⁹ esu. The real and imaginary parts of the third-order susceptibility were found in very good agreement with experimental results and theoretical predictions reported by Smith et al. [D.D. Smith, Y. Yoon, R.W. Boyd, Y.K. Cambell, L.A. Baker, R.M. Crooks, M. George, J. Appl. Phys. 86 (1999) 6200].     

Homogeneous Spaces with Sections

We study homogeneous Riemannian manifolds all of whose geodesics can be mapped by some isometry into a fixed homogeneous, connected, totally geodesic submanifold, called section. We show that these spaces are locally symmetric if the section is two-dimensional and give non-symmetric counterexamples with higher-dimensional sections.Mathematics Subject Classification (2000): 53C35, 53C30, 53C22, 57S15     

Development of a colourimetric pH assay for the quantification of pyrethroids based on glutathione-S-transferase

Recombinant glutathione-S-transferases (GSTs) can be used as analytical tools for the development of simple insecticide quantification assays. This assay explores the ability of pyrethroids to promote inhibition of the GST-catalysing 1-chloro-2,4-dinitrobenzene (CDNB)/glutathione (GSH) conjugation reaction. The sensing scheme is based on the pH change occurring in a weak buffer system by the GST reaction, which is measured using a spectrophotometer and the dye indicator bromothymol blue (616 nm). Practical use depends on the recognition affinity of the GST for insecticides, inhibition kinetics, enzyme stability and compatibility with the detection assay. In this study we compared the recombinant GSTs AgGSTD1-6 and AdGSTD1-1 from the mosquito vectors Anopheles gambiae and Anopheles dirus, respectively, with high affinity for pyrethroids, for their suitability for detecting pyrethroids in vector disease control programmes. The results showed that AgGSTD1-6 was the most suitable enzyme with the best structural stability at higher temperatures (T _m = 57°C) and pH optima in the alkaline range (pH 7.7). Using the AgGSTD1-6, we subsequently developed a pH - change colourimetric assay for detecting pyrethroids. Linear calibration curves were obtained for deltamethrin (R ² = 0.99) with useful concentration ranges of 0–50 µg mL^?1. The effect of temperature in the range 25–40°C on the pyrethroid quantification assay was negligible. The assay was validated with extracts from insecticide sprayed surfaces and found to be reproducible and reliable compared with the standard reverse-phase high performance liquid chromatography (Rp-HPLC) method. The potential of the assay for monitoring insecticide residues in the frame of insecticide based malaria control interventions is discussed.     

Efficient Atropodiastereoselective Access to 5,5′‐Bis‐1,2,3‐triazoles: Studies on 1‐Glucosylated 5‐Halogeno 1,2,3‐Triazoles and Their 5‐Substituted Derivatives as Glycogen Phosphorylase Inhibitors

Whereas copper‐catalyzed azide–alkyne cycloaddition (CuAAC) between acetylated β‐D ‐glucosyl azide and alkyl or phenyl acetylenes led to the corresponding 4‐substituted 1‐glucosyl‐1,2,3‐triazoles in good yields, use of similar conditions but with 2 equiv CuI or CuBr led to the 5‐halogeno analogues (>71 %). In contrast, with 2 equiv CuCl and either propargyl acetate or phenyl acetylene, the major products (>56 %) displayed two 5,5′‐linked triazole rings resulting from homocoupling of the 1‐glucosyl‐4‐substituted 1,2,3‐triazoles. The 4‐phenyl substituted compounds (acetylated, O‐unprotected) and the acetylated 4‐acetoxymethyl derivative existed in solution as a single form (d.r.>95:5), as shown by NMR spectroscopic analysis. The two 4‐phenyl substituted structures were unambiguously identified for the first time by X‐ray diffraction analysis, as atropisomers with aR stereochemistry. This represents one of the first efficient and highly atropodiastereoselective approaches to glucose‐based bis‐triazoles as single atropisomers. The products were purified by standard silica gel chromatography. Through Sonogashira or Suzuki cross‐couplings, the 1‐glucosyl‐5‐halogeno‐1,2,3‐triazoles were efficiently converted into a library of 1,2,3‐triazoles of the 1‐glucosyl‐5‐substituted (alkynyl, aryl) type. Attempts to achieve Heck coupling to methyl acrylate failed, but a stable palladium‐associated triazole was isolated and analyzed by ¹H NMR and MS. O‐Unprotected derivatives were tested as inhibitors of glycogen phosphorylase. The modest inhibition activities measured showed that 4,5‐disubstituted 1‐glucosyl‐1,2,3‐triazoles bind weakly to the enzyme. This suggests that such ligands do not fit the catalytic site or any other binding site of the enzyme.     

1,4-Benzoxazin-2-ones,benzo[d]oxazoles and 2H-1,4-benzoxazines from the reaction of 2-(methoxyimino)benzen-1-ones with arylacetates,arylacetic acids and trans- stilbene

10-(Methoxyimino)phenanthrene-9-one 1 reacts thermally with the arylacetic derivatives 2(a-j ) to yield the corresponding 1,4-benzoxazin-2-ones 4(a-d,f ) and benzo[d]oxazoles 5(a-e,g ). Similarly, reaction of the monoximes 7a, 7b with compounds 2a, 2d respectively affords 8a, 8b , while action of trans-stilbene on the monoximes 1, 7a, 7b leads to the 1,4-benzoxazines 10, 11, 13 , obtained along with the corresponding 2-phenyloxazoles 5a, 8a, 8c and compound 12 .     

Plastic pellets sorptive extraction: Low-cost,rapid and efficient extraction of polycyclic aromatic hydrocarbons from environmental waters

For the first time, plastic pellets, a low-cost and easy to reach industrial raw material, are reported as an efficient sorbent material for the laboratory extraction of polycyclic aromatic hydrocarbons (PAHs) from environmental waters. The proposed methodology, termed plastic pellets sorptive extraction (P2SE), consisted of a two-step procedure whereby target analytes were initially adsorbed onto the surface of three low-density polyethylene (LDPE) pellets and then desorbed using microliters of an organic solvent. Interphase mass transfer was greatly accelerated by means of vortex agitation. Organic extracts were analyzed by means of liquid chromatography-fluorescence detection. Different experimental parameters were controlled and the optimum conditions found were: three LDPE pellets (∼80 mg) added to 20 mL aqueous sample (20% w:v NaCl) followed by vortex agitation at 3000 rpm; for desorption, the three LDPE pellets were immersed in 100 μL of acetonitrile and the mixture was shaken at 3000 rpm for 5 min using the vortex agitator. The calculated calibration curves gave high levels of linearity yielding coefficients of determination (r²) greater than 0.9913. The precision of the proposed method was found to be good and the limits of the detection were calculated in the low ng L⁻¹ level. Matrix effects were determined by applying the proposed method to spiked river water, treated municipal wastewater and seawater samples. To compensate for the low recoveries of the more hydrophobic PAHs in spiked effluent wastewater and seawater samples the standard addition methodology was applied. The proposed method was applied to the determination of target pollutants in real seawater samples using the standard addition method. Overall, the performance of the proposed P2SE method suggests that the use of inexpensive and easy to reach sorbent materials for extracting analytes in the laboratory merits more intensive investigation.