QSAR model for the prediction of bio-concentration factor using aqueous solubility and descriptors considering various electronic effects

The in silico modelling of bio-concentration factor (BCF) is of considerable interest in environmental sciences, because it is an accepted indicator for the accumulation potential of chemicals in organisms. Numerous QSAR models have been developed for the BCF, and the majority utilize the octanol/water partition coefficient (log P) to account for the penetration characteristics of the chemicals. The present work used descriptors from a variety of software packages for the development of a multi-linear regression model to estimate BCF. The modelled data set of 473 diverse compounds covers a wide range of log BCF values. In the proposed QSAR model, most of the variation is described by the calculated solubility in water. Other contributing descriptors describe, for instance, hydrophobic surface area, hydrogen bonding and other electronic effects. The model was validated internally by using a variety of statistical approaches. Two external validations were also performed. For the former validation, a subset from the same data source was used. The 2nd external validation was based on an independent data set collected from different resources. All validations showed the consistency of the model. The applicability domain of the model was discussed and described and a thorough outlier analysis was performed.

[1]  Mathilde Romberg,et al.  The UNICORE Grid infrastructure , 2002, Sci. Program..

[2]  J.C. Dearden,et al.  Improved prediction of fish bioconcentration factor of Hydrophobic Chemicals , 2004, SAR and QSAR in environmental research.

[3]  Emilio Benfenati,et al.  Grid Computing for the Estimation of Toxicity: Acute Toxicity on Fathead Minnow (Pimephales promelas) , 2007, GCCB.

[4]  Zhide Hu,et al.  The accurate QSPR models to predict the bioconcentration factors of nonionic organic compounds based on the heuristic method and support vector machine. , 2006, Chemosphere.

[5]  J. Bardwell,et al.  Disulfide Bond Formation in Prokaryotes and Eukaryotes , 2002 .

[6]  J. Dearden,et al.  Linear QSAR regression models for the prediction of bioconcentration factors by physicochemical properties and structural theoretical molecular descriptors. , 2007, Chemosphere.

[7]  David E. Booth,et al.  Chemometrics: Data Analysis for the Laboratory and Chemical Plant , 2004, Technometrics.

[8]  Frank A. P. C. Gobas,et al.  A review of bioconcentration factor (BCF) and bioaccumulation factor (BAF) assessments for organic chemicals in aquatic organisms , 2006 .

[9]  Kazuya Nakao,et al.  The usefulness of an artificial membrane accumulation index for estimation of the bioconcentration factor of organophosphorus pesticides. , 2009, Chemosphere.

[10]  D. Mackay,et al.  Partition coefficient and bioaccumulation of selected organic chemicals , 1977 .

[11]  Egon L. Willighagen,et al.  The Chemistry Development Kit (CDK): An Open-Source Java Library for Chemo-and Bioinformatics , 2003, J. Chem. Inf. Comput. Sci..

[12]  Liu Shushen,et al.  Predicting bioconcentration factor values of organic pollutants based on MEDV descriptors derived QSARs , 2007 .

[13]  Paola Gramatica,et al.  An Update of the BCF QSAR Model Based on Theoretical Molecular Descriptors , 2005 .

[14]  M. Karelson,et al.  Correlation of Boiling Points with Molecular Structure. 1. A Training Set of 298 Diverse Organics and a Test Set of 9 Simple Inorganics , 1996 .

[15]  Joop L. M. Hermens,et al.  Quantitative structure-activity relationships for the toxicity and bioconcentration factor of nitrobenzene derivatives towards the guppy (Poecilia reticulata) , 1987 .

[16]  S Dimitrov,et al.  Base-line model for identifying the bioaccumulation potential of chemicals , 2005, SAR and QSAR in environmental research.

[17]  Bin Wang,et al.  Development and assessment of quantitative structure-activity relationship models for bioconcentration factors of organic pollutants , 2009 .

[18]  S. L. Mayo,et al.  DREIDING: A generic force field for molecular simulations , 1990 .

[19]  Ekaterina Gordeeva,et al.  Rapid conversion of molecular graphs to three-dimensional representation using the MOLGEO program , 1993, J. Chem. Inf. Comput. Sci..

[20]  John H. Montgomery,et al.  Groundwater Chemicals Desk Reference , 1989 .

[21]  J. Timbrell.  Principles of biochemical toxicology , 1991 .

[22]  E. Benfenati,et al.  Comparative Quantitative Structure–Activity–Activity Relationships for Toxicity to Tetrahymena pyriformis and Pimephales promelas , 2007, Alternatives to laboratory animals : ATLA.

[23]  E. Meissner,et al.  Special applications of fluorinated organic compounds. , 2006, Journal of Hazardous Materials.

[24]  Shu-Shen Liu,et al.  Molecular electronegativity distance vector model for the Prediction of bioconcentration factors in fish , 2008, Journal of molecular modeling.

[25]  J. Stewart.  Optimization of parameters for semiempirical methods I. Method , 1989 .

[26]  Salvador Sagrado,et al.  Modelling bioconcentration of pesticides in fish using biopartitioning micellar chromatography. , 2005, Journal of chromatography. A.

[27]  Robert S. Boethling,et al.  Improved method for estimating bioconcentration/bioaccumulation factor from octanol/water partition coefficient , 1999 .

[28]  Mohammad Hossein Fatemi,et al.  Prediction of bioconcentration factor using genetic algorithm and artificial neural network , 2003 .

[29]  J Devillers,et al.  Nonlinear dependence of fish bioconcentration on n-octanol/water partition coefficient. , 1993, SAR and QSAR in environmental research.

[30]  Shu-Shen Liu,et al.  QSPR model for bioconcentration factors of nonpolar organic compounds using molecular electronegativity distance vector descriptors , 2010, Molecular Diversity.

[31]  S D Dimitrov,et al.  Non-linear modeling of bioconcentration using partition coefficients for narcotic chemicals , 2002, SAR and QSAR in environmental research.

[32]  James J. P. Stewart,et al.  MOPAC: A semiempirical molecular orbital program , 1990, J. Comput. Aided Mol. Des..

[33]  Safiye Sag Erdem,et al.  QSPR Study on the Bioconcentration Factors of Nonionic Organic Compounds in Fish by Characteristic Root Index and Semiempirical Molecular Descriptors , 2004, J. Chem. Inf. Model..

[34]  S. Tao,et al.  Estimation of bioconcentration factors of nonionic organic compounds in fish by molecular connectivity indices and polarity correction factors. , 2000, Chemosphere.

[35]  Shu-Shen Liu,et al.  A new predictive model for the bioconcentration factors of polychlorinated biphenyls (PCBs) based on the molecular electronegativity distance vector (MEDV). , 2008, Chemosphere.

[36]  Uko Maran,et al.  Open Computing Grid for Molecular Science and Engineering , 2006, J. Chem. Inf. Model..

[37]  D Mackay,et al.  Correlation of bioconcentration factors. , 1982, Environmental science & technology.

[38]  C. Steinbeck,et al.  Recent developments of the chemistry development kit (CDK) - an open-source java library for chemo- and bioinformatics. , 2006, Current pharmaceutical design.

[39]  Igor V. Tetko,et al.  Virtual Computational Chemistry Laboratory – Design and Description , 2005, J. Comput. Aided Mol. Des..

[40]  Y. Li,et al.  Estimation of bioconcentration factors using molecular electro-topological state and flexibility , 2008, SAR and QSAR in environmental research.

[41]  S. Tao,et al.  Prediction of fish bioconcentration factors of nonpolar organic pollutants based on molecular connectivity indices. , 1999, Chemosphere.

[42]  Uko Maran,et al.  Modeling the Toxicity of Chemicals to Tetrahymena pyriformis Using Heuristic Multilinear Regression and Heuristic Back-Propagation Neural Networks , 2007, J. Chem. Inf. Model..

[43]  Bernd Schuller,et al.  Chemomentum - UNICORE 6 Based Infrastructure for Complex Applications in Science and Technology , 2007, Euro-Par Workshops.

[44]  E. E. Kenaga,et al.  Relationship between water solubility, soil sorption, octanol-water partitioning, and concentration of chemicals in biota , 1980 .

[45]  M. Hardy.  A comparison of the fish bioconcentration factors for brominated flame retardants with their nonbrominated analogues , 2004, Environmental toxicology and chemistry.

[46]  Gareth Thomas,et al.  Use of quantitative structural analysis to predict fish bioconcentration factors for pesticides. , 2009, Journal of agricultural and food chemistry.

[47]  P. Isnard,et al.  Estimating bioconcentration factors from octanol-water partition coefficient and aqueous solubility , 1988 .

[48]  Douglas J. Klein,et al.  Modeling the bioconcentration factors and bioaccumulation factors of polychlorinated biphenyls with posetic quantitative super-structure/activity relationships (QSSAR) , 2006, Molecular Diversity.

[49]  D. Meent,et al.  Transport, Accumulation and Transformation Processes , 1995 .

[50]  J. Gasteiger,et al.  ITERATIVE PARTIAL EQUALIZATION OF ORBITAL ELECTRONEGATIVITY – A RAPID ACCESS TO ATOMIC CHARGES , 1980 .

[51]  M. Karelson,et al.  The proposal of architecture for chemical splitting to optimize QSAR models for aquatic toxicity. , 2008, Chemosphere.

[52]  Uko Maran,et al.  Docking and Virtual Screening Using Distributed Grid Technology , 2009 .

[53]  A. Zhang,et al.  Progressive study and robustness test of QSAR model based on quantum chemical parameters for predicting BCF of selected polychlorinated organic compounds (PCOCs). , 2001, Chemosphere.

[54]  Richard F. Gunst,et al.  Applied Regression Analysis , 1999, Technometrics.

[55]  Emilio Benfenati,et al.  A new hybrid system of QSAR models for predicting bioconcentration factors (BCF). , 2008, Chemosphere.

[56]  Gilman D. Veith,et al.  Predicting bioconcentration factors of highly hydrophobic chemicals. Effects of molecular size , 2002 .

[57]  S. Petrocelli,et al.  An evaluation of using partition coefficients and water solubility to estimate bioconcentration factors for organic chemicals in fish , 1980 .

[58]  John Dearden,et al.  QSAR Modeling of Bioaccumulation , 2004 .

[59]  Terry S. Carlton,et al.  Correlation of Boiling Points with Molecular Structure for Chlorofluoroethanes , 1998, J. Chem. Inf. Comput. Sci..

[60]  Svetoslav H. Slavov,et al.  Legitimate Utilization of Large Descriptor Pools for QSPR/QSAR Models , 2008, J. Chem. Inf. Model..

[61]  Paola Gramatica,et al.  QSAR Modeling of Bioconcentration Factor by theoretical molecular descriptors , 2003 .

[62]  K. Roy,et al.  QSPR of the bioconcentration factors of non-ionic organic compounds in fish using extended topochemical atom (ETA) indices , 2006, SAR and QSAR in environmental research.

[63]  Alan R. Katritzky,et al.  QSPR and QSAR Models Derived Using Large Molecular Descriptor Spaces. A Review of CODESSA Applications , 1999 .