QSAR-based toxicity classification and prediction for single and mixed aromatic compounds

Quantitative structure-activity relationships (QSARs) based on the octanol/water partition coefficient were employed to predict acute toxicities of 36 substituted aromatic compounds and their mixtures. In this study, the model developed by Verhaar et al. was modified and used to calculate octano/water partition coefficients of chemical mixtures. To validate the model, acute toxicities of these chemicals were measured to Vibrio fischeri in terms of EC50. The results indicated that the obtained QSAR models could be used to predict toxicities of samples consi sting of these substituted aromatic compounds, individually or in combinations. The obtained equations were proved to be robust enough by using the leave-one-out test method. By classifying these chemicals into two groups, polar and non-polar, the toxicities of chemical mixtures within each group can be predicted accurately from their calculated partition coefficients.     

硝基芳烃对梨形四膜虫急性毒性的定量构效关系研究

硝基芳烃衍生物是炸药、染料、农药和有机合成的重要原料或中间体,应用极为广泛,但它们均为有毒物质,是我国松花江中主要有机污染物之一,其中有些化合物已被美国环保局列为优先监测污染物[1].     

Structure-Toxicity Relationships for Aliphatic Compounds Encompassing a Variety of Mechanisms of Toxic Action to Vibrio fischeri

Abstract

QSARs based upon the logarithm of the octanol-water partition coefficient, logP, and energy of the lowest unoccupied molecular orbital, E_LUMO were developed to model the toxicity of aliphatic compounds to the marine bacterium Vibrio fischeri. Statistically robust, hydrophobic-dependent QSARs were found for chloroalcohols and haloacetonitriles. Modelling of the toxicity of the haloesters and the diones required the use of terms to describe both hydrophobicity and electrophilicity. The differences in intercepts, slopes, and fit of these models suggest different electrophilic mechanisms occur between classes, as well as within the diones and haloesters. In order to model globally the toxicity of aliphatic compounds to V. fischeri, all the data determined in this study were combined with those determined previously for alkanones, alkanals, and alkenals. A highly predictive two-parameter QSAR [pT₁₅ = 0.760(log P) ?0.625(E _LUMO) ?0.466; n = 63, s = 0.462, r ² = 0.846, F = 171, Pr > F = 0.0001] was developed for the combined data that models across classes and is independent of mechanisms of action. The toxicity of these compounds to V. fischeri compares well to the toxicity (50% population growth inhibition) to the ciliate Tetrahymena pyriformis (r ² = 0.850).     

Mg-promoted reductive coupling of aromatic carbonyl compounds with trimethylsilyl chloride and bis(chlorodimethylsilyl) compounds

Mg-promoted reductive coupling of aromatic carbonyl compounds (1) with chlorosilanes, such as trimethylsilyl chloride (TMSCl:2), 1,2-bis(chlorodimethylsilyl)ethane (3) and 1,5-dichlorohexamethyltrisiloxane (4), in N,N-dimethylformamide (DMF) at room temperature brought about selective and facile reductive formation of both of carbon-silicon and oxygen-silicon bonds to give the corresponding α-trimethylsilylalkyl trimethylsilyl ethers (5) and cyclic siloxanes (6), (7) in moderate to good yields, respectively. The present facile and selective coupling may be initiated through electron transfer from Mg metal to aromatic carbonyl compounds (1).     

A metal-catalyst-free oxidative coupling of anilines to aromatic azo compounds in water using bleach

A simple route toward the synthesis of symmetrical and unsymmetrical aromatic azo compounds through oxidative coupling of anilines using widely available NaOCl is presented. This metal catalyst-free protocol is performed in water and affords the desired products in high yields.     

Fiber-packed needle for dynamic extraction of aromatic compounds

A fiber-packed needle was developed as a novel extraction device for gas-chromatographic analysis of trace organic compounds in aqueous samples. In the extraction device, a bundle of the polymer-coated filaments as the sorbent material was longitudinally packed into a specially designed needle. The extraction was made by pumping the aqueous sample solution into the needle extraction device, and the subsequent desorption process was carried out with a flow of desorption solvent through the needle in a heated gas chromatograph injector. The needle device showed an excellent thermal stability for repeated use without any deterioration of extraction performance, and no carryover effect was observed after the optimization of the desorption conditions. Additionally, the extraction efficiency of the fiber-packed needle could be enhanced by optimizing the number of packed filaments. The selectivity for various compounds could be also tuned using an appropriate combination of the fibrous medium and the coating polymer. The relative standard deviation for run to run was from 3.88 to 4.55% (n = 5), and that for needle to needle was 7.21% (n = 3), clearly suggesting a good repeatability of the needle extraction technique developed. Upon successful optimization of the extraction conditions, a rapid extraction of trace organic compounds from an aqueous sample matrix was successfully demonstrated, where each extraction process was completed within 10 min.     

An efficient and regioselective iodination of electron-rich aromatic compounds using N-chlorosuccinimide and sodium iodide

An efficient and regioselective method for iodination of electron-rich aromatic compounds was found using N-chlorosuccinimide and sodium iodide in AcOH with short reaction times. This method is also applicable to non-benzenoid aromatic or heteroaromatic compounds.     

Properties of subcritical water as an eluent for reversed-phase liquid chromatography—Disruption of the hydrogen-bond network at elevated temperature and its consequences

The use of subcritical water as an eluent for reversed-phase liquid chromatography is further explored. Shape selectivity as well as thermodynamic values for solute transfer were measured and compared to those seen with traditional ambient methanol/water and acetonitrile/water mobile phases. Linear solvation energy analysis was also used to analyze extrapolated values of the retention factor in pure water at ambient temperatures (k^′_w${k^{\prime }}_w$) for subcritical water and ambient hydroorganic mobile phases. Results indicate that it is likely that a large disruption in the hydrogen-bonding network of water at high temperatures causes unique chromatographic selectivity, as well as prohibits accurate extrapolation from high temperature to ambient conditions using pure water. Additionally, subcritical water was not found to be a suitable mobile phase for determining k^′_w${k^{\prime }}_w$ for use in estimating octanol/water partition coefficients.     

Comparative study of capillary zone electrophoresis and micellar electrokinetic chromatography for the separation of twelve aromatic sulphonate compounds

Summary Two modes of capillary electrophoresis (CE), capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography (MEKC), were investigated for the separation of 12 aromatic sulphonate compounds. In CZE, although the voltage applied, the buffer concentration and the pH were optimized for effective separation of the compounds studied, under the best conditions four of the five amino compounds coeluted, as did naphthalene-1-sulphonic acid and naphthalene-2-sulphonic acid. In MEKC, sodium dodecyl sulphate (SDS) and Brij 35 were chosen as the anionic and nonionic surfactants and the effect of the concentration of micelles was examined. The effect of adding methanol as the organic modifier was also investigated with each of these micellar systems. All the analytes, including the isomers, were completely separated by use of MEKC with Brij 35 but when SDS was used only 11 compounds were separated because two amino compounds coeluted.     

Validation and extension of a similarity-based approach for prediction of acute aquatic toxicity towards Daphnia magna

Quantitative structure–activity relationship (QSAR) models for predicting acute toxicity to Daphnia magna are often associated with poor performances, urging the need for improvement to meet REACH requirements. The aim of this study was to evaluate the accuracy, stability and reliability of a previously published QSAR model by means of further external validation and to optimize its performance by means of extension to new data as well as a consensus approach. The previously published model was validated with a large set of new molecules and then compared with ChemProp model, from which most of the validation data were taken. Results showed better performance of the proposed model in terms of accuracy and percentage of molecules outside the applicability domain. The model was re-calibrated on all the available data to confirm the efficacy of the similarity-based approach. The extended dataset was also used to develop a novel model based on the same similarity approach but using binary fingerprints to describe the chemical structures. The fingerprint-based model gave lower regression statistics, but also less unpredicted compounds. Eventually, consensus modelling was successfully used to enhance the accuracy of the predictions and to halve the percentage of molecules outside the applicability domain.     

Rapid and mild sulfonylation of aromatic compounds with sulfonic acids via mixed anhydrides using Tf2O

An efficient and direct sulfonylation of aromatic compounds with sulfonic acids is described via mixed anhydrides in short reaction times using Tf₂O in nitromethane at room temperature.     

β-Cyclodextrin epichlorohydrin copolymer as a solid-phase extraction adsorbent for aromatic compounds in water samples

A novel solid-phase extraction (SPE) procedure for trace aromatic compounds in water samples has been developed using 12 aromatic compounds as model compounds and GC-MS and UV spectrophotometry for detection. The method is based on the fact that β-cyclodextrin (β-CD) epichlorohydrin (ECH) copolymer (β-CDEP) can extract non-ionized aromatic compounds quantitatively from aqueous samples. The polymer used is a colorless, transparent and insoluble solid with a maximum capacity of 0.82 μmol aromatic compounds per gram. It was synthesized by co-polymerization of β-CD and ECH and characterized by FT-IR and UV. β-CDEP does not contain double bonds, and therefore it does not have appreciable absorbance in the UV region. The optimum pH range for the extraction of aromatic compounds is 2.5-5.0. The method has high extraction efficiency with the recoveries between 90 and 101% for aromatic compounds at 0.02-1.67 ppm levels, and the analytes can be easily eluted by methanol washing after preconcentration.     

Prediction of pesticide acute toxicity using two-dimensional chemical descriptors and target species classification

Previous modelling of the median lethal dose (oral rat LD₅₀) has indicated that local class-based models yield better correlations than global models. We evaluated the hypothesis that dividing the dataset by pesticidal mechanisms would improve prediction accuracy. A linear discriminant analysis (LDA) based-approach was utilized to assign indicators such as the pesticide target species, mode of action, or target species - mode of action combination. LDA models were able to predict these indicators with about 87% accuracy. Toxicity is predicted utilizing the QSAR model fit to chemicals with that indicator. Toxicity was also predicted using a global hierarchical clustering (HC) approach which divides data set into clusters based on molecular similarity. At a comparable prediction coverage (~94%), the global HC method yielded slightly higher prediction accuracy (r² = 0.50) than the LDA method (r² ~ 0.47). A single model fit to the entire training set yielded the poorest results (r² = 0.38), indicating that there is an advantage to clustering the dataset to predict acute toxicity. Finally, this study shows that whilst dividing the training set into subsets (i.e. clusters) improves prediction accuracy, it may not matter which method (expert based or purely machine learning) is used to divide the dataset into subsets.     

Palladium(II)-catalyzed carboxylation of benzene and other aromatic compounds with carbon monoxide under very mild conditions

Aromatic compounds such as benzene, toluene, chlorobenzene, anisole, and naphthalene were carboxylated by palladium(II) acetate catalyst with carbon monoxide in the presence of potassium peroxodisulfate in trifluoroacetic acid (TFA) at room temperature under atmospheric pressure. The aromatic carboxylic acids were formed in good yields; for example, the carboxylation of benzene with carbon monoxide proceeds quantitatively under the optimal conditions.     

Evaluation of coelectroosmotic capillary zone electrophoresis for the rapid analysis of twelve aromatic sulphonate compounds

Summary Coelectroosmotic capillary zone electrophoresis (CZE) has been investigated as a means of rapid analysis of twelve aromatic sulphonate compounds. The main factors affecting reversal of electroosmotic flow (EOF)—type of osmotic modifier and concentration-were studied. Two types of osmotic modifier, an alkylammonium salt (cetyltrimethylammonium bromide, CTAB) and a cationic polyelectrolyte (hexadimentrine bromide, HDB) were investigated. The composition of the running buffers was optimized according to the characteristics of each osmotic modifier. A concentration of HDB as low as 0.0001% (w/v) was used successfully to provide a stable and reversed EOF.