Coral: QSAR models for acute toxicity in fathead minnow (Pimephales promelas)

CORrelation And Logic (CORAL) is a software that generates quantitative structure activity relationships (QSAR) for different endpoints. This study is dedicated to the QSAR analysis of acute toxicity in Fathead minnow (Pimephales promelas). Statistical quality for the external test set is a complex function of the split (into training and test subsets), the number of epochs of the Monte Carlo optimization, and the threshold that is a criterion for dividing the correlation weights into two classes rare (blocked) and not rare (active). Computational experiments with three random splits (data on 568 compounds) indicated that this approach can satisfactorily predict the desired endpoint (the negative decimal logarithm of the 50% lethal concentration, in mmol/L, pLC₅₀). The average correlation coefficients (r²) are 0.675 ± 0.0053, 0.824 ± 0.0242, 0.787 ± 0.0101 for subtraining, calibration, and test set, respectively. The average standard errors of estimation (s) are 0.837 ± 0.021, 0.555 ± 0.047, 0.606 ± 0.049 for subtraining, calibration, and test set, respectively. The CORAL software together with three random splits into subtraining, calibration, and test sets can be downloaded on the Internet ( http://www.insilico.eu/coral/ ). © 2012 Wiley Periodicals, Inc.     

On some novel extended topochemical atom (ETA) parameters for effective encoding of chemical information and modelling of fundamental physicochemical properties

Extended topochemical atom (ETA) indices developed by our group have been extensively applied in our previous reports for toxicity and ecotoxicity modelling in the field of quantitative structure–activity relationships (QSARs). In the present study these indices have been further explored by defining additional novel parameters to model n-octanol–water partition coefficient (two data sets; n?=?168 and 139), water solubility (n?=?193), molar refractivity (n?=?166), and aromatic substituent constants π, MR, σ _m, and σ _p (n?=?99). All the models developed in the present study have undergone rigorous internal and external validation tests and the models have high statistical significance and prediction potential. In terms of Q ² and r ² values the models developed for the datasets of whole molecules are better than those previously reported, with topochemically arrived unique (TAU) indices on the same datasets of chemicals. An attempt has also been made to develop models using non-ETA topological and information indices. Interestingly, ETA and non-ETA models have been found to have similar predictive capacity.     

Determination of poly(dimethyl)siloxane-water partition coefficients for selected hydrophobic organic chemicals using 14C-labeled analogs

Aqueous solutions of (14)C-labeled analogs of seven hydrophobic organic chemicals (HOCs) were subject to solid-phase microextraction (SPME) under static conditions to assess their multi-compartment distribution and to compare poly(dimethyl)siloxane (PDMS)-water partition coefficients (K(f) values) with previously reported values. To accomplish this, a protocol for quantitative desorption of radiolabelled HOCs from SPME fibers using hexane was developed. Time series extractions indicated that loading of SPME fibers had reached steady-state by day 8 for PCBs 52, 77 and 153, phenanthrene, benzo[a]pyrene, p,p'-DDT and p,p'-DDE. The recovery of spiked radioactivity among the (residual) aqueous phase, the PDMS coating, and all remaining wetted experimental surfaces ranged between 80 and 120%. K(f) values based on (14)C-labeled analogs were in good agreement with previously published values that were determined at (or closely approaching) equilibrium conditions and without significant chemical depletion and/or uncorrected system losses. Because it allows for the direct determination of HOCs associated with the residual aqueous and experimental surface compartments, the use of radiolabelled HOC analogs is a powerful tool in discriminating among competing sorptive compartments encountered in most SPME fiber calibration methodologies employed to date.     

Conjugate phosphination of cyclic and acyclic acceptors using Rh(I)-phosphine or Rh(I)-carbene complexes. Probing the mechanism with chirality at the silicon atom or the phosphorus atom of the Si-P reagent

The Rh(I)-catalyzed conjugate phosphinyl transfer from an Si-P reagent to an electron-deficient acceptor requires individual protocols for cyclic and acyclic α,β-unsaturated carbonyls and carboxyls. While 1,4-addition to cyclic acceptors is catalyzed by a Rh(I)-phosphine complex, a Rh(I)-carbene complex is needed to promote conjugate phosphination of acyclic acceptors. General procedures for both systems are reported. Aside from monophosphine-derived Si-P reagents as phosphinide sources, dppe- as well as dppp-derived reagent having two Si-P units do also participate in this reaction. The mechanism of this Rh(I)-catalyzed activation of the Si-P reagent is still under debate. Control experiments with enantiopure silicon-stereogenic and racemic phosphorus-stereogenic Si-P reagents support a catalysis commencing with transmetalation rather than oxidative addition. Preparation and full characterization data of the Si-P compounds used in this investigation is included.     

Trace element determination of high-purity chemicals for the processing of semiconductors with high-resolution ICP-mass spectrometry using stable isotope dilution analysis (IDA)

The demand for trace element analysis in many fields of application has significantly increased in the last few years. Accuracy is fundamental to analysis and the importance of accurate measurements is widely accepted. Yet most instrumental analytical methods are relative methods and accuracy is established by using certified reference materials for method validation and calibration or by use of a definitive method as isotope dilution analysis (IDA). In this work a new high-resolution ICP mass spectrometer Finnigan MAT “ELEMENT”, which provides mass spectral resolution of 300 up to 7500 and thus eliminates most of the spectral interferences quadrupol mass analyzers are suffering from, is applied in combination with IDA to evaluate the capabilities of these techniques to the accurate determination of element traces in processing chemicals for semiconductor production.     

Molecular structure-activity relationships for the oxidation of organic compounds using mesoporous silica catalysts derivatised with bis(halogeno)dioxomolybdenum(VI) complexes

Mo K-edge XAFS spectra have been measured for ordered mesoporous silica MCM-41 grafted with the complexes [MoO2X2(thf)2] (X=Cl, Br). For grafting reactions in the absence of triethylamine, materials with 1 wt. % Mo are obtained; the Mo K-edge EXAFS results indicate the co-existence of isolated surface-fixed monomeric species [MoO2[(-O)3SiO]2(thf)(n)] and [MoO2[(-O)3SiO]X(thf)(n)]. When Et3N is used in the grafting reactions, materials with 4 wt. % Mo are obtained. The EXAFS data for the material prepared using [MoO2Cl2(thf)2] and Et3N indicate the presence of dinuclear species with two Mo(VI) centres, each with two Mo=O groups and each linked by one or two oxo bridges (Mo...Mo 3.27 A). The molybdenum centres in the material prepared using the dibromo complex comprise mainly isolated four-coordinate dioxomolybdenum(VI) and trioxomolybdenum(VI) monomeric species, with a small contribution from dimeric species. All materials were further characterised in the solid state by powder X-ray diffraction, N2 adsorption analysis, MAS NMR (13C, 29Si) and FTIR spectroscopy. The derivatised MCMs perform differently as catalysts in the liquid-phase oxidation of various olefins and alcohols with tert-butyl hydroperoxide. The highest alkene epoxidation activity was recorded for the catalysts with low metal loading, whereas the material containing oxo-bridged dimers had the highest activity for oxidation of alcohols. The recyclability of all the catalysts was tested: the catalytic activity of the derivatised materials tended to stabilize with ageing.     

Alkynyliodonium salts in organic synthesis. Development of a unified strategy for the syntheses of (-)-agelastatin A and (-)-agelastatin B

The total syntheses of natural agelastatin A and agelastatin B were accomplished via a strategy that utilized an alkynyliodonium salt --> alkylidenecarbene --> cyclopentene transformation to convert a relatively simple amino alcohol derivative to the functionalized core of the agelastatin system. Subsequent manipulations delivered debromoagelastatin, which served as a precursor to both agelastatin A and agelastatin B. Alkylidenecarbene insertion chemoselectivity issues were explored en route to the final targets.     

Development of an element-selective monitoring system for adsorbable organic halogens (AOX) with plasma emission spectrometric detection for quasi-continuous waste-water analysis

An automated quasi-continuously-operating monitor has been developed for element-selective analysis of adsorbable organic halogens (AOX) in water. After extensive optimization the automatic method was applied to the analysis of standard solutions and real waste water samples to prove its analytical applicability. The new instrument is based on the element-selective analysis of halogens by means of a spectroscopic detection system consisting of a microwave-induced helium plasma excitation source (TM010-type; developed in this laboratory) and the plasma emission detector (PED) which operates with oscillating narrow-band interference filters. After enriching the organic components on activated charcoal and pyrolysis in an oxygen stream at 950 degrees C, in accordance with DIN/EN 38409,H14/1485, interfering CO2 and H2O gas generated during combustion is removed from the analytes in the so-called ELSA-system (element-selective AOX-analyzer). For focused injection into the plasma excitation source the analytes (hydrogen halides) are trapped in a deactivated fused silica capillary at -180 degrees C; this is followed by identification and quantification on the basis of element-specific emission of radiation in the VIS and NIR-region (chlorine 837.6 nm, fluorine 685.6 nm). Bromine and iodine could not be detected with satisfactory inter-element selectivity, because of spectral interferences caused by matrix elements, and so results from the respective single-element investigations for determination of AOBr and AOI are not presented. The procedure has been validated and the analytical performance has been examined by calibration with p-chlorophenol and p-fluorophenol. The limit of detection was 1.1 microg (absolute) for chlorine and 6.6 microg (absolute) for fluorine.     

Biosynthesis of the verrucarins and roridins. Part 4. The mode of incorporation of (3R)-((5R)-5-3H)-mevalonate into verrucarol. Evidence for the identity of the C(11)-hydrogen atom of the trichothecane skeleton with the (5R)-hydrogen atom of (3R)-mevalonic acid.

Incorporation of (3R)-[(5R)-5-³H]-mevalonate into verrucarin followed by hydrolyses to verrucarol (2) and transformation of the latter to the spirolactol 5 and the spirolactone 6 successively, demonstrate the identity of the C(11)-hydrogen of the trichothecane skeleton with the 5-‘pro-R’ hydrogen atom of (3R)-mevalonate.