Showing papers in "Sar and Qsar in Environmental Research in 1995"
TL;DR: QSAR screening of the TSCA Inventory has prioritized thousands of existing chemicals for possible regulatory testing of: 1) persistent bioaccumulative chemicals, and 2) the high ecotoxicity of specific discrete organic chemicals.
Abstract: As testing is not required, ecotoxicity or fate data are available for approximately 5% of the approximately 2,300 new chemicals/year (26,000 + total) submitted to the US-EPA. The EPA's Office of Pollution Prevention and Toxics (OPPT) regulatory program was forced to develop and rely upon QSARs to estimate the ecotoxicity and fate of most of the new chemicals evaluated for hazard and risk assessment. QSAR methods routinely result in ecotoxicity estimations of acute and chronic toxicity to fish, aquatic invertebrates, and algae, and in fate estimations of physical/chemical properties, degradation, and bioconcentration. The EPA's Toxic Substances Control Act (TSCA) Inventory of existing chemicals currently lists over 72,000 chemicals. Most existing chemicals also appear to have little or no ecotoxicity or fate data available and the OPPT new chemical QSAR methods now provide predictions and cross-checks of test data for the regulation of existing chemicals. Examples include the Toxics Release Inventory (TRI), the Design for the Environment (DfE), and the OECD/SIDS/HPV Programs. QSAR screening of the TSCA Inventory has prioritized thousands of existing chemicals for possible regulatory testing of: 1) persistent bioaccumulative chemicals, and 2) the high ecotoxicity of specific discrete organic chemicals.
65 citations
TL;DR: A general outline of the project is given and results of experimental work within this project will be published in the proceedings of the 6th International Workshop on QSAR in Environmental Sciences and will appear in this same journal.
Abstract: In 1993, an international project on QSAR has been started with funding from the Commission of the European Union. The first part of the project is focused on preparing an overview of existing models for the prediction of environmental parameters such as bioconcentration, sorption, degradation and ecotoxicity. Emphasis will be given to defining the limitations of the models. Since all models, including QSARs, have their limitations, it is important that these limitations are known in case QSARs are actually used and applied within the risk assessment context. The second part of the project is directed towards experimental research on new developments with emphasis on the use of multivariate techniques and quantum chemical properties. In this short paper, a general outline of the project will be given, as well as some first results. Results of experimental work within this project will be published in the proceedings of the 6th International Workshop on QSAR in Environmental Sciences and will appe...
44 citations
TL;DR: A lot of work has been done to develop QSAR models for tropospheric degradation of commercial chemicals that will be based on calculated quantum chemical descriptors, and the best results of the high-level ab initio molecular orbital calculations are presented and discussed.
Abstract: For the majority of commercial chemicals present in the troposphere, the reaction with OH radicals during the day and with NO3 radicals at night are the most important abiotic pathways for their degradation and removal from the troposphere. Today, there are only a couple of methods available for estimating the reactivity of commercial chemicals with tropospheric radicals, which are not class specific, he Atkinson fragment contribution method and QSAR models, based on a linear correlation of OH (NO3) radical reactivity with the corresponding ionization energies, allow a rapid estimation of the rate constants of OH or NO3 radicals for various classes of organic compounds. Both methods are described and their limitations are discussed. A lot of work has been done to develop QSAR models for tropospheric degradation of commercial chemicals that will be based on calculated quantum chemical descriptors. This fast expanding area of QSAR research is presented and evaluated. Particular emphasis is given to the precision of various methods as well as to the latest results from our laboratory. The recent dramatic development in computing technology enables to precisely calculate energy profiles of tropospheric reactions with OH radicals. The semiempirical and ab initio molecular orbital calculations have been performed for hydrogen abstraction reactions for several classes of tropospheric pollutants. The best results of the high-level ab initio molecular orbital calculations are presented and discussed.
43 citations
TL;DR: The role of non-transitivity of the tolerance relation in estimating properties using similarity methods in estimating mutagenicity of 95 aromatic amines and boiling points of a large set of over 2,900 compounds is examined.
Abstract: Molecular similarity methods were used in selecting K nearest neighbors and in estimating mutagenicity of 95 aromatic amines and boiling points of a large set of over 2,900 compounds. Similarity is analyzed in terms of the concept of tolerance space. Specifically, the role of non-transitivity of the tolerance relation in estimating properties using similarity methods is examined.
36 citations
TL;DR: A model representing chemical similarities and differences is achieved and a set of 20 structurally different congeners is suggested to be used in future quantitative structure-activity relationships (QSARs) for screening of the toxicological and biochemical effects of the PCBs.
Abstract: By characterizing the 154 tetra- through heptachlorinated biphenyl (PCB) congeners with a multitude of physico-chemical descriptors, a model representing chemical similarities and differences is ac ...
35 citations
TL;DR: In this article, a spreadsheet method for calculation of aquatic toxicity of such nonionic surfactant mixtures is presented, based on a combination of the Konemann narcosis QSAR and mixture toxicity equations based on the principle of concentration addition.
Abstract: Ethoxylated alcohols are the most extensively used nonionic surfactants in detergent products. The application of QSAR to their aquatic toxicity is complicated by the fact that they are multicomponent mixtures, the parent alcohols being often mixtures of isomers and homologues, each one being ethoxylated to varying degrees. A spreadsheet method for calculation of aquatic toxicity of such nonionic surfactant mixtures is presented. The method is based on a combination of the Konemann narcosis QSAR and mixture toxicity equations based on the principle of concentration addition. Log P values used in the spreadsheet calculations are themselves calculated by spreadsheet formulae based on the Leo and Hansch method modified by incorporation of the position dependent branching factor originally applied to linear alkylbenzene sulphonates. Close agreement between calculated and experimental EC50 values (48 hr Daphnia tests) is obtained for a range of ethoxylated alcohols having a diversity of branching patt...
35 citations
TL;DR: A large data set of Microtox® toxicity results was used to derive a general QSAR model and the obtained results were compared with those obtained from a principal components regression analysis.
Abstract: A large data set of Microtox® toxicity results was used to derive a general QSAR model. Chemicals were described by means of a modified autocorrelation method. The autocorrelation vectors were generated from atomic contributions encoding the hydrophobicity and molar refractivity of the molecules. A three-layer backpropagation neural network was used to design the model. The obtained results were compared with those obtained from a principal components regression analysis.
31 citations
TL;DR: In this paper, the results of a series of efforts to develop QSAR models for polycyclic aromatic hydrocarbons (PAHs) whose toxicity is enhanced by the ultraviolet radiation present in sunlight were reviewed.
Abstract: This paper reviews the results of a series of efforts to develop QSAR models for aromatic chemicals whose toxicity is enhanced by the ultraviolet radiation present in sunlight. Photoinduced toxicity of polycyclic aromatic hydrocarbons (PAHs) was found to be a result of competing factors: structural (such as molecular stability and light absorbance) and external (irradiation energy and intensity). These two factors interact, producing a complex, multilinear relationship between toxicity and electronic structure. The HOMO-LUMO gap provided a useful ground-state index to explain the persistence, light absorption, and eventually, the photoinduced toxicity of PAHs. The derived QSAR clearly distinguished phototoxic differences between pairs of structurally similar PAHs, such as phenanthrene and anthracene, benzo [a] anthracene and tetracene, et cetera. Those PAHs exhibiting photoinduced toxicity were consistently within a specific range of the electronic parameter. Further modeling revealed a significa...
29 citations
TL;DR: QSAR analysis reveals a significant three parameter equation, and confirms the importance of hydrophobicity and descriptors of reactivity for the comprehension and the prediction of the toxicity of the benzonitriles.
Abstract: The toxicities of 34 benzonitriles to Tetrahymena pyriformis have been measured. Structure-activity relationships indicate that for these compounds different mechanisms of toxic action are taking place dependent on the nature of the substituent. Benzonitrile itself, some halogenated and the toluene derivatives model as non-polar narcotics; more polar substituents model well as polar narcotics; whilst the nitro and aldehyde substituted benzonitriles, and compounds that may be metabolised to benzoquinone are shown to exhibit considerable excess toxicity and, thus, the probability is that they are acting by a specific mechanism of action. After the removal of two outliers, QSAR analysis reveals a significant three parameter equation, and confirms the importance of hydrophobicity and descriptors of reactivity for the comprehension and the prediction of the toxicity of the benzonitriles.
23 citations
TL;DR: The relative toxicity (log IGC-1(50)) of 54 selected alkanones, both aliphatic and aromatic, as well as, alkenones and alkynones was evaluated in the static Tetrahymena pyriformis population growth assay and represented the nonpolar narcosis mechanism of toxic action.
Abstract: The relative toxicity (log IGC-1(50)) of 54 selected alkanones, both aliphatic and aromatic, as well as, alkenones and alkynones was evaluated in the static Tetrahymena pyriformis population growth assay. Excess toxicity, an indicator of bioreactivity, was associated only with the alpha-beta unsaturated alkenones and alkynones. Moreover, the alkynones were found to be more toxic than corresponding alkenones. A high quality 1-octanol/water partition coefficient (log Kow) dependent structure-toxicity relationship, log IGC-1(50) = 0.86 (log Kow) - 2.27; r2 = 0.955, was developed for alkanones. This QSAR represented the nonpolar narcosis mechanism of toxic action. Toxicity of alkenones was predicted by the highest-occupied-molecular-orbital energy (HOMO), log IGC-1(50) = -3.474 (HOMO) -35.357; r2 = 0.897, and the difference between HOMO and the lowest-unoccupied-molecular-orbital energy (LUMO), log IGC-1(50) = -3.559 (HOMO-LUMO gap) - 36.106; r2 = 0.903. The alpha-beta unsaturated ketones are considered soft electrophiles. Moreover, the toxicity of the aliphatic alkanones and alkenones was predicted by log Kow and LUMO, log IGC-1(50) = 0.69 (log Kow) - 2.55 (LUMO) + 0.05; r2 = 0.852.
22 citations
TL;DR: An extended comparison of two of the major components of a quantitative similarity measure, the similarity coefficient and the standardisation method, when used with one common form of field-based data, viz. the steric and electrostatic fields used in a CoMFA analysis is described.
Abstract: There is increasing interest in the development of field-based, similarity-searching systems, in which a user's target structure is matched against the structures in a database to find those that are most similar to it, on the basis of some quantitative similarity measure. This paper describes an extended comparison of two of the major components of such a measure, the similarity coefficient and the standardisation method, when used with one common form of field-based data, viz. the steric and electrostatic fields used in a CoMFA analysis. Our results show that there is little difference between the performances of the various coefficients and standardisation methods when tested in simulated property-prediction experiments. Accordingly, any of the coefficients and standardisation methods are appropriate for use in a field-based similarity searching system.
TL;DR: In this article, a thermodynamic model was used to derive molar (subcooled) liquid volume, heat of vaporization and Scatchard-Hildebrand solubility parameters of polychlorinated biphenyls.
Abstract: A thermodynamic model (SOFA) was used to derive molar (subcooled) liquid volume, heat of vaporization and Scatchard-Hildebrand solubility parameters of polychlorinated biphenyls. Differences in molar volume and heat of vaporization between cis-trans isomers and between enantiomers were accounted for by specific fragment contributions and by an increase or decrease of molar volume and heat of vaporization when mixed cis-trans isomers or D-L enantiomers, respectively, occur. The SOFA model was extended by the inclusion of an orientational disorder entropy term. An accurate set of gas chromato-graphic relative retention times (N = 210) and semi-empirical data on heats of vaporization (N = 7) and molar volumes (N = 11) was used for the derivation. An extremely accurate prediction was obtained. The mean deviations between calculated and experimental values were close to experimental errors. The corresponding correlation coeficients amounted to r = 0.9989, 0.9988, and 0.99996 for heat of vaporization, ...
TL;DR: The joint project aims at an estimation through validated QSAR models of the physical-chemical, ecotoxicity and toxicity endpoints which are included in the regulation and where experimental data will become available in IUCLID (International Unified Chemicals Information Database).
Abstract: Following a previous collaborative EU/EPA project focussed on QSAR predictions for a selection of new chemicals which had been notified in the EU, a similar exercise was started in 1993 on existing chemicals. In a first phase, the project addresses the High Production Volume (HPV) chemicals which are produced or imported at levels above a 1000t/year in the EU and 454t/year in the US. The relevant EU (Annex 1 of Existing Chemicals Regulation No. 793/93) and US-EPA lists contain 1036 and 2881 organic substances respectively of which HPV 749 chemicals are in common. The joint project aims at an estimation through validated QSAR models of the physical-chemical, ecotoxicity and toxicity endpoints which are included in the regulation and where experimental data will become available in IUCLID (International Unified Chemicals Information Database). Next to EC-JRC (ECB) and US-EPA, various laboratories in the EU are contributing to the project and recently, two institutes in Japan have joined in this pro...
TL;DR: The complementation and partial replacement of in vivo (eco)toxicological testing by in vitro assays depends on two criteria: the sensitivity of the tests to reliably detect environmentally relevant concentrations of toxicants and the specificity of the assays to provide an unambiguous classification of toxicant by modes of action.
Abstract: A concept for toxicity assessments based on in vitro assays of variant levels (i.e., from whole cells to isolated enzymes) is presented. Due to the complexity of organisms of different species, it is evident that no single in vitro test can represent the entire spectrum of toxic potency of chemicals, rather a carefully designed battery of tests has to be employed to account for the various targets attacked in organisms yielding the different modes of action. Cytotoxicity tests like the Neutral-Red Assay predominantly reflect non-specific toxicity, which can be modelled according to a log P OW dependent baseline QSAR. Specific toxicants (e.g., decouplers, acetylcholinesterase inhibitors or photosystem II inhibitors) may be identified based on according in vitro tests and eventually modelled by the respective mode of action related QSARs employing also, e.g., steric or polarizability descriptors to account for specific interactions. The complementation and partial replacement of in vivo (eco)toxico...
TL;DR: In this article, the authors attempted to estimate reduction potential from structure using semi-empirical quantum chemical models for a diverse set of chemicals, including benzoquinoids, naphthoquinones, phenols and nitrobenzenes, and found that small absolute charge on the carbonyl carbon in the quinone moiety correlated with more positive one-electron reduction.
Abstract: Benzoquinones, naphthoquinones and aziridinylbenzoquinones, can be reduced by flavoproteins to semiquinones that react with molecular oxygen to form superoxide anion with the subsequent regeneration of the parent compounds. This redox cycling, a form of futile metabolism, produces reactive oxygen species and depletes the reducing equivalents of cells without concomitant energy production. The ability of a toxicant to redox cycle is related to its one-electron reduction potential, and this study attempted to estimate reduction potential from structure using semi-empirical quantum chemical models for a diverse set of chemicals. The results of this study suggest that one-electron reduction potentials, within structural classes of benzoquinones, naphthoquinones, phenols and nitrobenzenes, can be estimated from local and global electronic indices that are related to delocalization. Smaller absolute charge on the carbonyl carbon in the quinone moiety correlated with more positive one-electron reduction...
TL;DR: In this article, a log P model was derived from a stepwise regression analysis based on a training set of 800 organic molecules presenting highly diverse structures using the autocorrelation method using the structural fragmental values of Rekker.
Abstract: A log P model was derived from a stepwise regression analysis based on a training set of 800 organic molecules presenting highly diverse structures. Chemicals were described by means of the autocorrelation method using the structural fragmental values of Rekker. Our approach was shown to be simpler and more efficient than the classical method of Rekker which generally requires the use of correction factors for calculating log P values.
TL;DR: Results show that semi-empirical molecular orbital descriptors are capable of describing the reaction kinetics within a homologous series of compounds, thus corroborating the hypothesis about mechanisms taking place in the environment.
Abstract: Existing models for the reductive dehalogenation reaction under environmentally relevant conditions use Hammett and Taft coefficients as descriptors. Drawbacks of these descriptors are the limited possibilities for interpretation in terms of reaction mechanisms, and the limited availability of these descriptors for more ‘exotic’ substituents. Therefore, in this study new descriptors are tested, using semi-empirical molecular orbital calculations. These descriptors are based on the energetic and electronic properties of the reaction sites and should be able to account for the systematics of the rate constants in a better way than substituent coefficient models. This approach is expected to give reliable estimates of the rate constants even for compounds containing less common structural features. Several relationships for a series of halogenated aromatics are presented here, relating the experimental rate constants to, among others, the calculated activation energy of the rate limiting step in the...
TL;DR: A flow-through test system to perform bioconcentration experiments with tubificids was evaluated in this article, where the ratio of the rate constants of uptake (k1) and clearance (k2) was calculated as: BCF = k 1/k2.
Abstract: A flow-through test system to perform bioconcentration experiments with tubificids was evaluated. First results were obtained for the hexachlorocyclohexane (HCH) isomers α-HCH, β−HCH, γ-HCH, and δ-HCH. Bioconcentration factors (BCFs) for these compounds were calculated from the ratio of the rate constants of uptake (k1) and clearance (k2) as: BCF = k1/k2. The BCFs of the 4 isomers increased with αfa;-HCH (32) γ-HCH (47) < δ-HCH (120) < β−HCH (190) [BCFs on fresh weight basis]. The differences in BCFs were mainly caused by different k1−values ranging form 5.4 (1/h) for α-HCH to 21.4 (1/h) for β−HCH. A comparison of the BCFs for tubificids with BCFs already known for zebrafish and juvenile rainbow trout showed nearly the same ranking for the isomeric HCHs. The absolute values of the BCFs however were about a factor of 10 lower for tubificids compared to the two fish species, even when associating them to the fat content.
TL;DR: From an analysis of the toxicity of phenols to rat embryos and anilines to embryo fibroblast cells a new type of toxicity is postulated for these classes of compounds.
Abstract: From an analysis of the toxicity of phenols to rat embryos and anilines to embryo fibroblast cells a new type of toxicity is postulated for these classes of compounds. Substituents which increase the electron density on the aromatic ring as estimated by σ+ or eHOMO increase potency. It is postulated that it is the radical form of the phenols and the anilines that accounts for their toxicity. The results are compared with QSAR for radical scavengers and oxidoreductases acting on phenols, anilines and carbazoles.
TL;DR: The procedure was employed to rank the relative ecological risk of forty-nine pesticides historically used in agricultural sites in the Walnut Creek watershed near Ames, lowa, USA, utilizing the ASTER (ASsessment Tools for the Evaluation of Risk) system.
Abstract: Ecological risk assessments can be used to establish the likelihood that an adverse effect will result from exposure to one or more chemicals. When evaluating contaminated sites with many chemicals present, risk assessors must grapple with the problem of quickly identifying the chemicals that are most likely to be of concern, based on effect and exposure assessment information. Many times data gaps exist and the risk assessor is left with decisions on which models to use to estimate the parameter of concern. In the present paper, a procedure is presented for ranking agrichemicals, utilizing the ASTER (ASsessment Tools for the Evaluation of Risk) system. The procedure was employed to rank the relative ecological risk of forty-nine pesticides historically used in agricultural sites in the Walnut Creek watershed near Ames, Iowa, USA. Empirical data from the ASTER system were used when available in the associated data-bases, and quantitative structure-activity relationships and expert systems were in...
TL;DR: In this article, the authors validate the use of the pH-metric technique (based on potentiometric titration) for measurements of pKa and log Pow of ionizable standard substances and herbicides.
Abstract: Knowing the values of pKa and partition coefficients between 1-octanol and water (Pow) of ionizable herbicides helps us to understand the movement of these compounds in plants and soil. However, shake-flask and high-pressure liquid chromatography (HPLC) techniques. though valuable for measurement of log Pow of herbicide molecules that do not ionize in aqueous solution, are difficult to use for ionizable molecules; this is especially so for molecules that form ion pairs having appreciable log Pow values, those with multiple ionizations and for bases with high pKa values. Our aim in this study was to validate the use of the pH-metric technique (based on potentiometric titration) for measurements of pKa and log Pow of ionizable standard substances and herbicides. The values obtained show good correlation with results from other techniques, including shake-flask and HPLC. The OECD Guideline for Testing of Chemicals 117, adopted 30th March 1989, describes the use of HPLC for the measurement of log Pow...
TL;DR: In this article, a review of real-number topological indices based on local vertex invariants (LOVIs) is presented, and the correlation ability of TIs is tested by modeling physico-chemical properties of large classes of compounds (alkanes, haloalkane, compounds with oxygen or sulfur heteroatoms), or smaller sets of biologically active compounds.
Abstract: For QSAR/QSPR studies, topological indices have proved to be among the most useful molecular descriptors. They are based on local vertex invariants (LOVIs). A review of last-generation real-number Tls based on new real-number LOVIs is presented. It is possible to reduce thus the intramolecular degeneracy of LOVIs for nonequivalent vertices, and the intermolecular degeneracy of TIs for nonisomorphic molecular graphs. The correlation ability of TIs was tested by modeling physico-chemical properties of large classes of compounds (alkanes, haloalkanes, compounds with oxygen or sulfur heteroatoms), or smaller sets of biologically active compounds. Prospects for modeling thermodynamic properties of chlorofluorocarbons and congeners are discussed.
TL;DR: Findings suggest that stereoelectronic descriptors for soft electrophilicity and one electron reduction potential may be useful in differentiating and predicting mechanisms of quinone toxicity.
Abstract: In an attempt to distinguish between the mechanisms by which electrophilic and redox cycling quinones induce the cyclosporine A (CyA)-sensitive mitochondrial membrane permeability transition, the ability of a series of quinones that span a broad range of electrophilic and redox cycling reactivities has been examined. The order of potency of quinone-induced Ca2+ release was 1,4-naphthoquinone (NQ) > 1,4-benzoquinone (BQ) > 2-methyl-1,4-naphthoquinone (MQ) > 2,3-dimethoxy-1,4-naphthoquinone (DiOMeNQ) > 2,3-dimethyl-1,4-naphthoquinone (DiMeNQ). Quinones with predominantly redox cycling reactivity, NQ (≤ 4 μM), MQ, DiOMeNQ and DiMeNQ, induced the CyA-sensitive membrane permeability transition. In contrast, NQ (> 4 μM) and BQ, induced rapid and complete Ca2+ release and membrane depolarization, but not swelling. Furthermore, BQ and NQ (> 4 μM)-induced effects were not prevented by CyA. Therefore, we maintain that, unlike MQ, DiOMeNQ, DiMeNQ and NQ (≤ 4μM), effects of BQ and NQ(> 4μM) on calcium flux a...
TL;DR: Improvements to the CASE method for hyperstructure generation are outlined, and the advantages of hyperstructures for data analysis, compression and visualisation are outlined.
Abstract: This paper summarises the results obtained from recent research at the University of Sheffield into the identification of topological pharmacophores and toxicophores. The published CASE and LOGANA methods were implemented, and several limitations revealed. The CASE method was improved by the use of atom pairs as descriptors. The LOGANA method was improved by the use of hyperstructures to reduce the number of variables available for combination. The paper outlines improvements to the method for hyperstructure generation, and the advantages of hyperstructures for data analysis, compression and visualisation. In the resultant scheme of operation, large datasets can be clustered on the basis of very general fragments, and then hyperstructures of the clusters input to LOGANA to highlight activating and inactivating substructures.
TL;DR: The assumptions, limitations, and methodology for the use of SARs to evaluate large sets of discrete organic chemicals are described and the general acceptance of toxicity predictions based on SARs is described.
Abstract: The Office of Pollution Prevention and Toxics (OPPT), United States Environmental Protection Agency (USEPA) routinely uses structure-activity relationships (SAR) for the aquatic hazard assessment of new chemicals submitted under Section 5 of the Toxic Substances Control Act (TSCA). With 15 years of experience and the general acceptance of toxicity predictions based on SARs, OPPT has expanded the use and application of the methodology to include existing chemicals used in printing, dry cleaning, and paint stripping. SAR analysis has also been used in the hazard evaluation of the U.S. and EU/OECD high production volume (HPV) chemicals. This paper describes the assumptions, limitations, and methodology for the use of SARs to evaluate large sets of discrete organic chemicals.
TL;DR: Using statistical criteria, this approach resulted in three QSARs with reasonably good predictive capabilities, originating from clusters 1639, 3472, and 5830, characterised by high correlation coefficients which describe the cluster itself very well but, due to the stringent bootstrap criterion, they are close to randomness.
Abstract: By means of clustering, one is able to manage large databases easily. Clustering according to structure similarity distinguished the several chemical classes that were present in our training set. All the clusters showed correlation of log WS with log K OW and melting point, except EINECS-cluster 1. This cluster contains only chemicals with melting points below room temperature, resulting in a log WS-log K OW , relationship. The observed weak correlation for this cluster is probably due to the insufficient number of available screens. Such a limited amount of screens allows relatively very different chemicals to share the same cluster. Using statistical criteria, our approach resulted in three QSARs with reasonably good predictive capabilities, originating from clusters 1639, 3472, and 5830. The models resulting from the smaller clusters 6873, 8154, and 16424 are characterised by high correlation coefficients which describe the cluster itself very well but, due to our stringent bootstrap criterio...
TL;DR: In this article, the Minimal Steric/Topologic Difference (MTD) method was used for general toxicity, hepatic cytosol receptor binding and aryl hydrocarbon hydroxylase induction on polychlorinated and polybrominated derivatives of dibenzo-p-dioxin, dibenzofuran and biphenyl.
Abstract: QSARs by the Minimal Steric/Topologic Difference (MTD)-method were performed for general toxicity, hepatic cytosol receptor binding and aryl hydrocarbon hydroxylase induction on polychlorinated and polybrominated derivatives of dibenzo-p-dioxin, dibenzofuran and biphenyl. Low energy conformations selected by molecular mechanics calculations and superpositions of the considered structures for the construction of the hypermolecule were performed using the COSMIC molecular modelling package. The multiconformational-MTD-method was used. Correlation coefficients of r = 0.8 to 0.9 were obtained as well as good cross-validation results, for series of up to 70 compounds. Conformational analysis of flexible molecules suggests their accommodation in the receptor site also in non planar conformations corresponding to the first stable one (minimum energy costs) above the global minimum. A common optimised receptor site can be attributed for all series of compounds, with a rather high symmetry, which suggests...
TL;DR: The steric properties modulating the mutagenic activity on S. typhimurium TA98 of a set of nitroaromatic compounds have been investigated using the CoMFA method and the overall lipophilicity and the energy of the lowest occupied molecular orbital have been employed as molecular descriptors.
Abstract: The steric properties modulating the mutagenic activity on S. typhimurium TA98 of a set of nitroaromatic compounds have been investigated using the CoMFA method. In addition to steric probe-ligand interaction energies, the overall lipophilicity and the energy of the lowest occupied molecular orbital have been employed as molecular descriptors.
TL;DR: The designed BPNN model based on designed training and test set not only gives the best model, but also the best predictability on an external validation set, compared both to linear models built with the same training and validation sets, and BPNN models based on randomly constructedTraining and test sets.
Abstract: In this study a systematic analysis of the predictive capabilities of models built with backpropagation neural networks (BPNN) is made to corroborate the hypothesis that BPNN is capable of modeling the interaction terms in group contribution models, without explicitly adding these as descriptors. The data used for comparison are reactivities of 275 organic compounds towards the atomospheric OH-radical. This dataset was selected because of the internal consistency, reliability and relatively large size of this dataset. While training the network, the minimal Mean Squared Error (MSE) on a test set was used as the stop criterion. This avoids overfitting on the training data, and is most likely to give the best generalizing network. A network trained with a designed training and test set is compared with networks trained on randomly constructed training and test sets. The BPNN model based on designed training and test set not only gives the best model, but also the best predictability on an external validation set, compared both to linear models built with the same training and validation sets, and BPNN models based on randomly constructed training and test sets. The performance of the designed BPNN model is comparable to an existing model which includes interaction terms.
TL;DR: The developed models for halogenated benzenes provide a valuable tool for estimating physico-chemical properties relevant to environmental chemistry and are optimised by a statistical procedure of selection of the most informative variables.
Abstract: This paper describes the development of multivariate QSAR models for halogenated benzenes. Four physico-chemical properties have been modelled: Boiling Point (BP), Melting Point (MP), Flash Point (FP) and Density (D). For the multivariate characterisation of this class of compounds 90 topological indices derived from the chemical formula were used. The models were calibrated on training sets selected by a D-optimal design and were optimised by a statistical procedure of selection of the most informative variables. The predictive capacity of the resulting models measured in terms of the parameter SDEP (Standard Deviation of the Errors of Predictions) were as follows; MP: ± 21 ±C (with MP ranging from −48° to 181°C); BP: ±13°C (75° to 286°C); D: ±0.14 (1.02 to 2.52 g/cm3); FP: ±17°C (-12 to 126°C). These data were confirmed “experimentally”, i.e., on external validation sets of compounds, the experimental values of the standard deviation of prediction errors were in fact as follows; MP: ±30°C; BP: ...