有机化学品生物富集因子定量结构-活性关系模型
|
摘要
依据经济合作与发展组织(OECD)关于定量结构-活性关系(QSAR)模型构建和使用导则,将780个有机化合物,以4:1的比例随机划分为训练集(624个化合物)和验证集(156个化合物),通过多元线性回归(MLR)方法构建了一个包含12个描述符的有机化合物鱼类生物富集因子(BCF)的QSAR模型。QSAR模型的调整决定系数R2ad j=0.809,去一法交叉验证系数Q2LOO=0.803,外部验证系数Q2EXT=0.732,表明模型具有较好的拟合优度、稳健性和预测能力。采用欧几里德距离方法表征模型应用域,通过威廉姆斯图分析模型离群点,并对模型进行机理解释。所构建的模型,可以用于预测应用域内有机化学品的生物富集因子。
According to the principles of development and validation for quantitative structure-activity relationship(QSAR) proposed by Organization for Economic Cooperation and Development(OECD), a QSAR model of bioconcentration factors in fish was built. 780 organic compounds were randomly divided into training set(624 compounds) and validation set(156 compounds) at a ratio of 4:1. The method that developed the model with 12 molecular descriptors was multiple linear regressions(MLR). The adjusted coefficient of determination(R2 adj), the leave-one-out cross validated coefficient(Q2 LOO) and external explained variance(Q2 EXT) was 0.809, 0.803 and 0.732,respectively. It is indicated that the model had satisfied goodness-of-fit, robustness and predictive ability. The application domain of the model was characterized by the Euclidean distance, outliers were analyzed by Williams andmechanism was interpreted subsequently. The obtained model was able to predict the BCF of organic chemicals within the application domain.
According to the principles of development and validation for quantitative structure-activity relationship(QSAR) proposed by Organization for Economic Cooperation and Development(OECD), a QSAR model of bioconcentration factors in fish was built. 780 organic compounds were randomly divided into training set(624 compounds) and validation set(156 compounds) at a ratio of 4:1. The method that developed the model with 12 molecular descriptors was multiple linear regressions(MLR). The adjusted coefficient of determination(R2 adj), the leave-one-out cross validated coefficient(Q2 LOO) and external explained variance(Q2 EXT) was 0.809, 0.803 and 0.732,respectively. It is indicated that the model had satisfied goodness-of-fit, robustness and predictive ability. The application domain of the model was characterized by the Euclidean distance, outliers were analyzed by Williams andmechanism was interpreted subsequently. The obtained model was able to predict the BCF of organic chemicals within the application domain.
引文
[1]Petoumenou M I,Pizzo F,Cester J.Comparison between bioconcentration factor(BCF)data provided by industry to the European Chemicals Agency(ECHA)and data derived from QSAR models[J].Environmental Research,2015,142:529-534
[2]Nendza M,Kühne R,Lombardo A.PBT assessment under REACH:Screening for low aquatic bioaccumulation with QSAR classifications based on physicochemical properties to replace BCF in vivo testing on fish[J].Science of the Total Environment,2018,616-617:97-106
[3]Gramatica P,Papa E.QSAR modeling of bioconcentration factor by theoretical molecular descriptors[J].QSAR and Combinatorial Science,2003,22:374-385
[4]Qin H,Chen J W,Wang Y,et al.Development and assessment of quantitative structure-activity relationship models for bioconcentration factors of organic pollutants[J].Chinese Science Bulletin,2009,54(4):628-634
[5]Piira G,Silda S,Roncaglioni A,et al.QSAR model for the prediction of bioconcentration factor using aqueous solubility and descriptors considering various electronic effects[J].SAR and QSAR in Environmental Research,2010,21(7-8):711-729
[6]Papa E,Dearden J C,Gramatica P.Linear QSAR regression models for prediction of bioconcentration factors by physicochemical properties and structural theoretical molecular descriptor[J].Chemosphere,2007,67(2):351-358
[7]Dearden J C.QSAR modeling of bioconcentration factor using hydrophobicity,hydrogen boding and topological descriptors[J].SAR and QSAR in Environmental Research,2010,7-8(21):671-680
[8]Piir G,Sild S,Maran U.Comparative analysis of local and consensus quantitative structure-activity relationship approaches for the prediction of bioconcentration factor[J].SAR and QSAR in Environmental Research,2013,24(3):175-199
[9]de Melo E B.A new quantitative structure-property relationship model to predict bioconcentration factors of polychlorinated biphenyls(PCBs)in fishes using E-state index and topological descriptors[J].Ecotoxicology and Environmental Safety,2012,75:213-222
[10]Mansouri K,Consonni V,Durjava M K,et al.Assessing bioaccumulation of polybrominated diphenyl ethers for aquatic species by QSAR modeling[J].Chemosphere,2012,89(4):433-444
[11]Jackson S H,Cowan-Ellsberry C E,Thomas G.Use of quantitative structural analysis to predict fish bioconcentration factors for pesticides[J].Journal of Agricultural and Food Chemistry,2009,57(3):958-967
[12]郑玉婷,乔显亮,杨先海,等.卤代有机化合物生物富集因子的定量结构-活性关系模型[J].生态毒理学报,2013,8(5):772-777Zheng Y T,Qiao X L,Yang X H,et al.Quantitative structure-activity relationship model for bioconcentration factors of halogenated organic compounds[J].Asian Journal of Ecotoxicology,2013,8(5):772-777(in Chinese)
[13]Lu X X,Tao S,Hu H Y,et al.Estimation of bioconcentration factors of nonionic organic compounds in fish by molecular connectivity indices and polarity correction factors[J].Chemosphere,2000,41(10):1675-1688
[14]Devillers J,Bintein S,Domine D.Comparison of BCFmodels based on log P[J].Chemosphere,1996,33(6):1047-1065
[15]Adolfsson-Erici M,kerman G,Mc Lachlan M S.Measuring bioconcentration factors in fish using exposure to multiple chemicals and internal benchmarking to correct for growth dilution[J].Environmental Toxicology and Chemistry,2012,31(8):1853-1860
[16]Inoue Y,Hashizume N,Yoshida T,et al.Comparison of bioconcentration and biomagnification factors for poorly water-soluble chemicals using common carp(Cyprinus carpio L.)[J].Archives of Environmental Contamination and Toxicology,2012,63(2):241-248
[17]Martin J W,Mabury S A,Solomon K R,et al.Bioconcentration and tissue distribution of perfluorinated acids in rainbow trout(Oncorhynchus mykiss)[J].Environmental Toxicology and Chemistry,2003,22(1):196-204
[18]Wei D B,Zhang A Q,Wu C D,et al.Progressive study and robustness test of QSAR model based on quantum chemical parameters for predicting BCF of selected polychlorinated organic compounds(PCOCs)[J].Chemosphere,2001,44(6):1421-1428
[19]Park J H,Lee H J.Estimation of bioconcentration factor in fish,adsorption coeficient for soil and sediments and interfacial tension with water for organic nonelectrolytes based on the linear salvation energy relationships[J].Chemosphere,1993,26(10):1905-1906
[20]Frisch M J,Trucks G W,Schlegel H B,et al.Gaussian09,revision a.02[CP].Wallingford,CT:Gaussian,Inc.,2009
[21]Talete S R L.DRAGON(Software for Molecular Descriptor Calculation)Version 6.0[CP/OL].[2018-07-18].http://www.talete.mi.it/
[22]Mohammad H F,Zahra G.Estimation of the volume of distribution of some pharmacologically important compounds from their structural descriptors[J].Journal of the Serbian Chemical Society,2011,76(7):1003-1014
[23]Zarei K,Salehabadi Z.The shuffling multivariate adaptive regression splines and adaptive neuro-fuzzy inference system as tools for QSPR study bioconcentration factors of polychlorinated biphenyls(PCBs)[J].Structural Chemistry,2012,23(6):1801-1807
[24]Fatemi M H,Ghorbannezhad Z.Estimation of the volume of distribution of some pharmacologically important compounds from their structural descriptors[J].Journal of the Serbian Chemical Society,2011,76(7):1003-1014
[25]Neely W B,Branson D R,Blau G E.Partition coefficient to measure bioconcentration potential of organic chemicals in fish[J].Environmental Science&Technology,1974,8(13):1113-1115
[26]Veith G D,De Foe D L,Bergstedt B V.Measuring and estimating the bioconcentration factor of chemicals on fish[J].Journal of Fisheries Research Board of Canada,l979,36:1040-1048
[27]胡海瑛,陶澍,卢晓霞.用片段常数法估算有机化合物在鱼体内的生物富集因子[J].环境科学学报,2001,21(3):271-276Hu H Y,Tao S,Lu X X.Predicting of BCFs in fish for organic chemicals using fragment constant method[J].Acta Scientiae Circumstantiae,2001,21(3):271-276(in Chinese)
[28]冯长君,唐自强,杨伟华,等.有机物在鱼体中生物富集因子的预测[J].石油化工高等学校学报,2009,22(1):31-40Feng C J,Tang Z Q,Yang W H,et al.Prediction of bioconcentration factors of nonionic organic compounds in fish[J].Journal of Petrochemical Universities,2009,22(1):31-40(in Chinese)
[29]Qin L T,Liu S S,Liu H L.QSPR model for bioconcentration factors of nonpolar organic compounds using molecular electronegativity distance vector descriptors[J].Molecular Diversity,2010,14(1):67-80
[30]Cui S H,Yang J,Liu S S,et al.Predicting bioconcentration factor values of organic pollutants based on MEDVdescriptors derived QSARs[J].Science in China Series B(Chemistry),2007,50(5):587-592
[31]Qin H,Chen J W,Wang Y,et al.Development and assessment of quantitative structure-activity relationship models for bioconcentration factors of organic pollutants[J].Chinese Science Bulletin,2009,54(4):628-634
[2]Nendza M,Kühne R,Lombardo A.PBT assessment under REACH:Screening for low aquatic bioaccumulation with QSAR classifications based on physicochemical properties to replace BCF in vivo testing on fish[J].Science of the Total Environment,2018,616-617:97-106
[3]Gramatica P,Papa E.QSAR modeling of bioconcentration factor by theoretical molecular descriptors[J].QSAR and Combinatorial Science,2003,22:374-385
[4]Qin H,Chen J W,Wang Y,et al.Development and assessment of quantitative structure-activity relationship models for bioconcentration factors of organic pollutants[J].Chinese Science Bulletin,2009,54(4):628-634
[5]Piira G,Silda S,Roncaglioni A,et al.QSAR model for the prediction of bioconcentration factor using aqueous solubility and descriptors considering various electronic effects[J].SAR and QSAR in Environmental Research,2010,21(7-8):711-729
[6]Papa E,Dearden J C,Gramatica P.Linear QSAR regression models for prediction of bioconcentration factors by physicochemical properties and structural theoretical molecular descriptor[J].Chemosphere,2007,67(2):351-358
[7]Dearden J C.QSAR modeling of bioconcentration factor using hydrophobicity,hydrogen boding and topological descriptors[J].SAR and QSAR in Environmental Research,2010,7-8(21):671-680
[8]Piir G,Sild S,Maran U.Comparative analysis of local and consensus quantitative structure-activity relationship approaches for the prediction of bioconcentration factor[J].SAR and QSAR in Environmental Research,2013,24(3):175-199
[9]de Melo E B.A new quantitative structure-property relationship model to predict bioconcentration factors of polychlorinated biphenyls(PCBs)in fishes using E-state index and topological descriptors[J].Ecotoxicology and Environmental Safety,2012,75:213-222
[10]Mansouri K,Consonni V,Durjava M K,et al.Assessing bioaccumulation of polybrominated diphenyl ethers for aquatic species by QSAR modeling[J].Chemosphere,2012,89(4):433-444
[11]Jackson S H,Cowan-Ellsberry C E,Thomas G.Use of quantitative structural analysis to predict fish bioconcentration factors for pesticides[J].Journal of Agricultural and Food Chemistry,2009,57(3):958-967
[12]郑玉婷,乔显亮,杨先海,等.卤代有机化合物生物富集因子的定量结构-活性关系模型[J].生态毒理学报,2013,8(5):772-777Zheng Y T,Qiao X L,Yang X H,et al.Quantitative structure-activity relationship model for bioconcentration factors of halogenated organic compounds[J].Asian Journal of Ecotoxicology,2013,8(5):772-777(in Chinese)
[13]Lu X X,Tao S,Hu H Y,et al.Estimation of bioconcentration factors of nonionic organic compounds in fish by molecular connectivity indices and polarity correction factors[J].Chemosphere,2000,41(10):1675-1688
[14]Devillers J,Bintein S,Domine D.Comparison of BCFmodels based on log P[J].Chemosphere,1996,33(6):1047-1065
[15]Adolfsson-Erici M,kerman G,Mc Lachlan M S.Measuring bioconcentration factors in fish using exposure to multiple chemicals and internal benchmarking to correct for growth dilution[J].Environmental Toxicology and Chemistry,2012,31(8):1853-1860
[16]Inoue Y,Hashizume N,Yoshida T,et al.Comparison of bioconcentration and biomagnification factors for poorly water-soluble chemicals using common carp(Cyprinus carpio L.)[J].Archives of Environmental Contamination and Toxicology,2012,63(2):241-248
[17]Martin J W,Mabury S A,Solomon K R,et al.Bioconcentration and tissue distribution of perfluorinated acids in rainbow trout(Oncorhynchus mykiss)[J].Environmental Toxicology and Chemistry,2003,22(1):196-204
[18]Wei D B,Zhang A Q,Wu C D,et al.Progressive study and robustness test of QSAR model based on quantum chemical parameters for predicting BCF of selected polychlorinated organic compounds(PCOCs)[J].Chemosphere,2001,44(6):1421-1428
[19]Park J H,Lee H J.Estimation of bioconcentration factor in fish,adsorption coeficient for soil and sediments and interfacial tension with water for organic nonelectrolytes based on the linear salvation energy relationships[J].Chemosphere,1993,26(10):1905-1906
[20]Frisch M J,Trucks G W,Schlegel H B,et al.Gaussian09,revision a.02[CP].Wallingford,CT:Gaussian,Inc.,2009
[21]Talete S R L.DRAGON(Software for Molecular Descriptor Calculation)Version 6.0[CP/OL].[2018-07-18].http://www.talete.mi.it/
[22]Mohammad H F,Zahra G.Estimation of the volume of distribution of some pharmacologically important compounds from their structural descriptors[J].Journal of the Serbian Chemical Society,2011,76(7):1003-1014
[23]Zarei K,Salehabadi Z.The shuffling multivariate adaptive regression splines and adaptive neuro-fuzzy inference system as tools for QSPR study bioconcentration factors of polychlorinated biphenyls(PCBs)[J].Structural Chemistry,2012,23(6):1801-1807
[24]Fatemi M H,Ghorbannezhad Z.Estimation of the volume of distribution of some pharmacologically important compounds from their structural descriptors[J].Journal of the Serbian Chemical Society,2011,76(7):1003-1014
[25]Neely W B,Branson D R,Blau G E.Partition coefficient to measure bioconcentration potential of organic chemicals in fish[J].Environmental Science&Technology,1974,8(13):1113-1115
[26]Veith G D,De Foe D L,Bergstedt B V.Measuring and estimating the bioconcentration factor of chemicals on fish[J].Journal of Fisheries Research Board of Canada,l979,36:1040-1048
[27]胡海瑛,陶澍,卢晓霞.用片段常数法估算有机化合物在鱼体内的生物富集因子[J].环境科学学报,2001,21(3):271-276Hu H Y,Tao S,Lu X X.Predicting of BCFs in fish for organic chemicals using fragment constant method[J].Acta Scientiae Circumstantiae,2001,21(3):271-276(in Chinese)
[28]冯长君,唐自强,杨伟华,等.有机物在鱼体中生物富集因子的预测[J].石油化工高等学校学报,2009,22(1):31-40Feng C J,Tang Z Q,Yang W H,et al.Prediction of bioconcentration factors of nonionic organic compounds in fish[J].Journal of Petrochemical Universities,2009,22(1):31-40(in Chinese)
[29]Qin L T,Liu S S,Liu H L.QSPR model for bioconcentration factors of nonpolar organic compounds using molecular electronegativity distance vector descriptors[J].Molecular Diversity,2010,14(1):67-80
[30]Cui S H,Yang J,Liu S S,et al.Predicting bioconcentration factor values of organic pollutants based on MEDVdescriptors derived QSARs[J].Science in China Series B(Chemistry),2007,50(5):587-592
[31]Qin H,Chen J W,Wang Y,et al.Development and assessment of quantitative structure-activity relationship models for bioconcentration factors of organic pollutants[J].Chinese Science Bulletin,2009,54(4):628-634