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.     

Measurement and estimation of rate constants for the reactions of hydroxyl radical with several alkanes and cycloalkanes

Relative rate experiments were used to measure ratios of chemical kinetics rate constants as a function of temperature for the reactions of OH with isobutane, isopentane, 2-methylpentane, 3-methylpentane, 2,3-dimethylbutane, 2,3-dimethylpentane, 2,4-dimethylpentane, 2,3,4-trimethylpentane, n-heptane, n-octane, cyclopentane, cyclohexane, and cycloheptane. The results have been used to calibrate a structure-reactivity rate constant estimation method for k(298 K) which, when combined with previously determined relationships between k(298 K) and the Arrhenius parameters, is capable of determining the temperature dependence accurately. The estimation method reproduces most of the observed rate data within experimental accuracy but appears to fail for 2,3-dimethylbutane, which has an anomalously high rate constant. Curvature in the Arrhenius plots at low temperatures is not present for compounds with a single type of C-H bond and, for compounds with different C-H bonds, is shown to be consistent with effects due to different group sites on the molecule.     

Temperature dependence of the rate constants for reactions of the carbonate radical with organic and inorganic reductants

Rate constants have been measured by pulse radiolysis for the reactions of the carbonate radical, CO₃^·?, with a number of organic and inorganic reactants as a function of temperature, generally over the range 5 to 80°C. The reactants include the substitution-inert cyano complexes of Fe^II, Mo^IV, and W^IV, the simple inorganic anions SO₃^2?, ClO₂^?, NO₂^?, I^?, and SCN^?, several phenolates, ascorbate, tryptophan, cysteine, cystine, methionine, triethylamine, and allyl alcohol. The measured rate constants ranged from less than 10⁵ to 3 × 10⁹ M^?1 s^?1, the activation energies ranged from ?11.4 to 18.8 kJ mol^?1, and the pre-exponential factors ranged from log A = 6.4 to 10.7. The activation energies for the metal complexes and inorganic anions generally decrease with increasing driving force for the reaction, as expected for an outer sphere electron transfer. For highly exothermic reactions, however, the activation energy appears to increase, probably reflecting the temperature dependence of diffusion. For many of the organic reactants, the activation energies were low and independent of driving force, suggesting that the oxidation is via an inner sphere mechanism.     

QSPR checking and validation: a case study with hydroxy radical reaction rate constant

Traditionally, QSAR and QSPR models have been fitted by splitting the available compounds into separate learning and validation sets. The model is then fitted to the learning set and assessed using the validation set. Cross-validation (CV) uses all available compounds for both purposes, so that the full body of available information is brought to bear on both the learning and the validation portions of the study. The price paid for this additional information is a substantially greater computational load. A common mistake in using CV is to omit some of the repetitive computations. This mistake leads to substantial bias in the assessment. A hydroxyl radical reaction rate dataset is used to illustrate the superiority of CV and the pitfalls from its improper execution when modeling using nearest neighbors, paralleling behavior in the well-studied linear model setting.     

Relationship between the properties of radical cations and the rate constants and the substitution patterns in electrophilic aromatic substitution

By a charge transfer mechanism for electrophilic aromatic substitution the logarithmic plot of overall rate constants for substitution against ionization potentials is correctly predicted. Also, orientation of substitution is found to be correlated with the hyperfine coupling constants of the aromatic radical cation. The presence of radical cations under the conditions of electrophilic substitution is discussed.     

Direct determination of rate constants for coupling between aromatic radical anions and alkyl and benzyl radicals by laser-flash photolysis

Coupling rates between the radicals methyl, n-, sec-, tert-butyl and benzyl (R.) and the aromatic radical anions of 1,4-dicyanonaphthalene, 9,10-dicyanoanthracene and fluorenone (A-.) have been obtained using a new laser-flash photolysis method. The radicals R. and the radical anions A-. were generated by a photoinduced electron transfer reaction between the aromatic compound A and the alkyl or benzyl triphenylborate anion RB(Ph)3-. For the first time the rate constants of the coupling reaction between methyl and benzyl radicals with aromatic radical anions have been obtained. For all the measured coupling rate constants an average value of k1 = 1.9 x 10(9) M-1 s-1 was found with a relatively small variation in the coupling rates (0.8-2.9 x 10(9) M-1 s-1). The results demonstrate that the coupling rate k1 is insensitive to changes in the steric and electronic properties of the radicals and the structure and standard potentials of the aromatic radical anions.     

Automated QSPR modeling and data curation of physicochemical properties using KNIME platform: Prediction of partition coefficients

In the last two decades, the volumes of chemical and biological data are constantly increasing. The problem of converting data sets into knowledge is both expensive and time-consuming, as a result a workflow technology with platforms such as KNIME, was built up to facilitate searching through multiple heterogeneous data sources and filtering for specific criteria then extracting hidden information from these large data. Before any QSAR modeling, a manual data curation is extremely recommended. However, this can be done, for small datasets, but for the extensive data accumulated recently in public databases a manual process of big data will be hardly feasible. In this work, we suggest using KNIME as an automated solution for workflow in data curation, development, and validation of predictive QSAR models from a huge dataset.In this study, we used 250250 structures from NCI database, only 3520 compounds could successfully pass through our workflow safely with their corresponding experimental log P, this property was investigated as a case study, to improve some existing log P calculation algorithms.     

Review of the QuEChERS method for the analysis of organic pollutants: Persistent organic pollutants,polycyclic aromatic hydrocarbons,and pharmaceuticals

In multi-residue pesticide analysis, the quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction method has replaced less efficient traditional extraction methods due to its many advantages. In addition to pesticide analysis, this method has been widely used for the detection and analysis of pharmaceuticals, polycyclic aromatic hydrocarbons (PAHs), and several persistent organic pollutants (POPs), including dioxins, polychlorinated biphenyls, perfluoroalkyl substances, and brominated flame retardants in food, biological, and environmental matrices. The analysis of PAHs and POPs is challenging due to the properties of the target compounds and their low concentrations in complex matrices. This review summarizes previously reported the QuEChERS extraction approaches to the analysis of a wide range of analytes. The QuEChERS approaches, which include dispersive solid phase extraction (d-SPE), have generally been combined with either gas chromatography–mass spectrometry (GC–MS) or liquid chromatography–mass spectrometry (LC–MS) analysis. Further on, in recent years, GC and LC-tandem mass spectrometry has been utilized with the QuEChERS extraction due to its high selectivity, sensitivity, and specificity. This enables the extraction methods for target analytes to be modified through the selection of different extraction solvents, salt formulations, and buffers for salting-out partitioning and the selection of different d-SPE and SPE sorbents for the clean-up process. The most significant advantage of this method is that concentration steps are not required. This review aims to provide an up-to-date overview of information regarding the modification of extraction techniques based on target compounds and sample matrices.     

Predicting rate constants of OH radical reactions with organic substances: advances for oxygenated organics through a molecular orbital HF/6-31G** approach

The molecular orbital OH (MOOH) approach is a perturbational quantum chemical method to predict rate constants of OH radical reactions with organic compounds. Going beyond previous AM1 parameterizations, a first ab initio implementation employing the HF/6-31G** level of calculation has been developed. For a set of 799 organic compounds with experimental rate constants, k _OH, varying over more than six orders of magnitude, the new MOOH-HF method is superior to both MOOH-AM1 and Atkinson’s increment scheme, yielding a predictive squared correlation coefficient (q ²) of 0.95 and a root-mean-square error of 0.29 log units. For oxygenated compounds, MOOH-HF shows significant improvements over MOOH-AM1, which holds in particular for aldehydes and ketones. The discussion includes detailed comparative analyses of the model performances for individual compound classes.     

Greening the organic chemistry laboratory: a comparison of microwave-assisted and classical nucleophilic aromatic substitution reactions

ABSTRACT

An experiment is described for the undergraduate organic chemistry lab which compares microwave-induced organic reaction enhancement (MORE) to that of more traditional synthetic procedures. MORE and traditional reflux procedures for substituting thiocyanate, ethylamine and diethylamine nucleophiles for bromide in nucleophilic aromatic substitution reactions on 1-bromo-2,4-dinitrobenzene are given. Recrystallization affords products of sufficient purity for characterization by ¹³C NMR, mass spectrometry and melting point. As students compare the two synthetic methods, MORE procedures are consistently observed to be quicker, easier, greener and result in higher yields. Student instructions, instructor notes and example NMR and mass spectra obtained by students are provided in Supplemental material.     

Global dynamics and transition state theories: Comparative study of reaction rate constants for gas-phase chemical reactions

In this review article, we present a systematic comparison of the theoretical rate constants for a range of bimolecular reactions that are calculated by using three different classes of theoretical methods: quantum dynamics (QD), quasi-classical trajectory (QCT), and transition state theory (TST) approaches. The study shows that the difference of rate constants between TST results and those of the global dynamics methods (QD and QCT) are seen to be related to a number of factors including the number of degrees-of-freedom (DOF), the density of states at transition state (TS), etc. For reactions with more DOF and higher density of states at the TS, it is found that the rate constants from TST calculations are systematically higher than those obtained from global dynamics calculations, indicating large recrossing effect for these systems. The physical insight of this phenomenon is elucidated in the present review.