From knowledge generation to knowledge archive. A general strategy using TOPS-MODE with DEREK to formulate new alerts for skin sensitization

A general strategy for knowledge flow concerning skin sensitization based on the combined use of TOPS-MODE and DEREK expert system is proposed. TOPS-MODE is used as a knowledge generator, while DEREK represents the knowledge archive. A TOPS-MODE classification model allows the identification of structural fragments and groups responsible for strong/moderate skin sensitization. These structural contributions are sorted, analyzed, and graphically displayed in an appropriate way allowing the identification of several structural alerts for skin sensitization. Nine structural alerts already implemented in DEREK are identified using this strategy. They comprise, among others, alkyl halides, aldehydes, alpha,beta-unsaturated compounds, aromatic amines, phenols, hydroquinone, isothiazolinone, and alkyl sulfonates. Four new hypotheses are generated using TOPS-MODE structural contributions to skin sensitization, which are not recognized as structural alerts by DEREK. They include the reduction of aromatic nitro groups and epoxidation reaction of double bonds as metabolic activation steps that can lead to reactive haptens which can trigger the skin sensitization mechanism. Another new alert is based on 1,2,5-thiadiazole-1,1-dioxide for which we have identified a possible mechanism explaining its strong skin sensitization profile. It is based on the existence of a tautomeric equilibrium and further reaction with nucleophiles, which are both supported by experimental evidence. Finally, we have identified a possible new mechanism for the skin sensitization of nonreactive compounds, which involves the formation of noncovalent complexes with proteins in a processing- and metabolism-independent way.     

Theoretical study of the interaction of molecular oxygen with copper clusters

A new method based on frontier orbital theory has been used to investigate the binding site of molecular oxygen to neutral and anion copper clusters. It has been shown that one can make useful predictions of the binding sites based on the knowledge of the donor local reactivity of the cluster using the condensed Fukui function, f(-)(Ff). In this way, it was found that Cu(3), Cu(5), and Cu(5)(-) have the highest reactivity toward molecular oxygen.     

Characterization of n-butyl acrylate centered triads in poly(n-butyl acrylate-co-carbon monoxide-co-ethylene) by isotopic labeling and two dimensional NMR

Poly(n-butylacrylate-co-carbon monoxide-co-ethylene) (polyEBC) samples prepared from 13C-labeled monomer, n-butyl acrylate, were characterized using two dimensional (2D) pulsed field gradient (PFG) 750 MHz NMR spectroscopy. To elucidate the complex structure of the terpolymer, 2D-1H/13C-heteronuclear single quantum coherence (HSQC) and heteronuclear multiple bond correlation (HMBC) experiments were conducted by selectively exciting the enhanced resonances in the spectra of two polymer samples, one polymer resulting from synthesis with 1-13C-n-butylacrylate monomer and a second polymer obtained from a synthesis with 2-13C-n-butylacrylate monomer. High-resolution 2D-NMR combined with 13C-labeling of the polymer greatly simplifies the 2D-NMR spectra, selectively enhances the weak peaks from low occurrence B-centered triad structures, and aids in their resonance assignments. In all experiments, the sample temperature was 120 degrees C, to ensure a homogeneous solution and sufficient molecular mobility. Electronic Supplementary Material: Supplementary material (1D 13C NMR spectra of the 13C-labeled and unlabeled polymers) is available in the online version of this article at http://dx.doi.org/100.1007/s00216-003-2402-3.     

Novel bifunctional acridine-acridinium conjugates: synthesis and study of their chromophore-selective electron-transfer and DNA-binding properties

Novel bifunctional conjugates 1-3, with varying polymethylene spacer groups, were synthesized, and their DNA interactions have been investigated by various biophysical techniques. The absorption spectra of these systems showed bands in the regions of 300-375 and 375-475 nm, corresponding to acridine and acridinium chromophores, respectively. When compared to 1 (Phi(f) = 0.25), bifunctional derivatives 2 and 3 exhibited quantitative fluorescence yields (Phi(f) = 0.91 and 0.98) and long lifetimes (tau = 38.9 and 33.2 ns). The significant quenching of fluorescence and lifetimes observed in the case of 1 is attributed to intramolecular electron transfer from the excited state of the acridine chromophore to the acridinium moiety. DNA-binding studies through spectroscopic investigations, viscosity, and thermal denaturation temperature measurements indicate that these systems interact with DNA preferentially through intercalation of the acridinium chromophore and exhibit significant DNA association constants (K(DNA) = 10(5)-10(7) M(-1)). Compound 1 exhibits chromophore-selective electron-transfer reactions and DNA binding, wherein only the acridinium moiety of 1 interacts with DNA, whereas optical properties of the acridine chromophore remain unperturbed. Among bifunctional derivatives 2 and 3, the former undergoes DNA mono-intercalation, whereas the latter exhibits bis-intercalation; however both of them interact through mono-intercalation at higher ionic strength. Results of these investigations demonstrate that these novel water-soluble systems, which exhibit quantitative fluorescence yields, chromophore-selective electron transfer, and DNA intercalation, can have potential use as probes in biological applications.     

Ullmann diaryl ether synthesis: rate acceleration by 2,2,6,6-tetramethylheptane-3,5-dione

[reaction: see text]. In the copper salt catalyzed ether formation from aryl bromides or iodides and phenols, 2,2,6,6-tetramethylheptane-3,5-dione (TMHD) was found to greatly accelerate the ordinarily difficult reaction, making it occur under more moderate temperatures and reaction times. A series of aryl halides and phenols were shown to form ethers in NMP as the solvent, cesium carbonate as the base, and CuCl and TMHD as the catalysts. The reaction was shown to tolerate electron-rich aryl bromides and electron-neutral phenols.     

Recent highlights in stationary phase design for open-tubular capillary electrochromatography

This review examines the most recent innovations made to achieve high performance in open-tubular capillary electrochromatography (OT-CEC) separations, focusing on the ingenious chemical and physical solutions made to increase the surface area and equip the stationary phase with exploitable selectivity. Among the approaches taken are chemically bonded ligands, etching with chemical bonding, sol-gels, molecularly imprinted polymers, porous layers, physically attached or adsorbed phases, and nanoparticle coatings. Particularly noteworthy are modern developments with macrocyclic receptor ligands, nanoparticles and open channel electrochromatography on-chip.     

Morphological characterization of elastin-mimetic block copolymers utilizing cryo- and cryoetch-HRSEM.

Elastin-mimetic block copolymers were produced by genetic engineering. Genetically driven synthesis permitted control of the final physiochemical characteristics of the block copolymers. We designed BB and BAB block copolymers in which the A-block was hydrophilic and the B-block was hydrophobic. By designing the copolymers in this manner, it was proposed that they would self-assemble into micellar aggregates that, at high concentration, would form thermoreversible hydrogels. To analyze the three-dimensional fine surface morphology of the copolymers, to the resolution level of a few nanometers, we employed cryo-HRSEM. This method provided vast expanses of the specimen in its frozen hydrated state for survey. In our initial cryo-HRSEM studies, we observed the protein filaments and micelles surrounded by lakes of vitreous ice. Upon examination at low and intermediate magnifications, there was an extensive honeycomb-like filamentous network. To delineate the fine morphology of the hydrogel network at high magnification and to greater depths, we cryoetched away unbound water from the sample surface, in high vacuum, prior to chromium deposition. By using this technique, we were able to visualize for characterization purposes the fine fibril networks formed from the micellar aggregates over the surface of the hydrogel.     

Studies on the reactivity of phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone: reactions with indole derivatives and other C-nucleophiles

[reaction: see text] Thermal decomposition of phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone (lawsone) in the presence of indole derivatives affords 3-acylated indoles existing in their enol forms, through a ring contraction and alpha,alpha'-dioxoketene formation reaction. The same reactants afford 3-(3-indolyl)-2-hydroxy-1,4-naphthoquinones in a copper-catalyzed reaction. Enamines, among other C-nucleophiles tested, give analogous results.     

Parallelization of three-center electron repulsion integrals

The parallelization of the three-center electron repulsion integrals arising from the variational fitting of the Coulomb potential is presented. A scheme for dynamical load balancing of the corresponding loop structure is discussed. The implementation in the density functional theory program deMon using the message passing interface is described. The efficiency of the parallelization is analyzed by selected benchmark calculations     

Analysis and toxicity of methomyl and ametryn after biodegradation

The controlled biodegradation of ametryn and methomyl has been performed, in accordance with the OECD Zahn-Wellens/EMPA procedure, by use of an enriched mixture of activated sludge collected from three domestic waste-water-treatment plants (WWTP). During the process concentrations of ametryn and methomyl in the water samples were isolated by solid-phase extraction (SPE); recovery rates were 98.9 and 93.2 for methomyl and ametryn, respectively. Liquid chromatography-mass spectrometry (LC-MS) was used to determine final pesticide concentrations and for metabolite identification.The efficiency of aerobic biodegradation of ametryn and methomyl was evaluated by measuring both the decrease in the concentration of the pesticides and global properties such as the chemical oxygen demand (COD). The acute toxicity of ametryn and methomyl was evaluated by use of the ToxAlert100 biological test, which is based on inhibition of the bioluminescence of Vibrio fischeri. There was significant correlation between results from primary and ultimate biodegradation and those from determination of toxicity. Pesticide concentrations were always reduced to below the limit of detection in less than 17 days. High COD removal (90-96%) was achieved in 28 and 18 days for methomyl and ametryn, respectively.