title: Theoretical study of the quantitative structure-activity relationships for the toxicity of dibenzo-p-dioxins.
abstract: Density functional theory calculations of polychlorinated dibenzo-p-dioxins (PCDDs) were carried out to obtain the electronic descriptors, polarizabilities, and traceless quadrupole moments of 76 PCDD congeners. No simple relationships were found for the electronic descriptors with the relevant aryl hydrocarbon receptor (AhR) binding affinities of PCDDs, which suggests that they alone may not be sufficient to explain the variation in toxicity. However, quantitative structure-activity relationships (QSARs) were developed with the polarizabilities and traceless quadrupole moments, explaining about 74% and 59% of variation in AhR binding affinities of PCDDs, respectively. To explain the nature of toxic interaction, a mathematical model based on the ligand-receptor binding and solute-solvent interaction was presented, and then a multiple regression analysis of all the above parameters was performed to evaluate the contributions of the parameters to the bonding affinities. Other data for PCDFs found in the literature were also included in the regression analysis to minimize data over-fitting. The results suggest that dispersion and electrostatic interactions are equally important for the interaction of PCDD/Fs with the AhR.
authors.affiliation: State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China.
authors.forename: Ya-Ying
authors.initials: YY
authors.lastname: Zhao
authors.forename: Fu-Ming
authors.initials: FM
authors.lastname: Tao
authors.forename: Eddy Y
authors.initials: EY
authors.lastname: Zeng
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D004147:Dioxins / Q000737:chemistry* / Q000633:toxicity*; D008956:Models, Chemical; D008962:Models, Theoretical; D021281:Quantitative Structure-Activity Relationship; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D012044:Regression Analysis; D013816:Thermodynamics
chemical_list: D004147:Dioxins; D018336:Receptors, Aryl Hydrocarbon; C020887:dibenzo(1,4)dioxin