QSARs for congener-specific toxicity of polyhalogenated dibenzo-p-dioxins with DFT and WHIM theory.
Polyhalogenated dibenzo-p-dioxins (PHDDs) have become the most notorious pollutants in the environment. However, the origin of their congener-specific toxicity is not well understood. For explaining the difference in toxicity between PHDDs as well as their potencies of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin O-deethylase (EROD) induction, quantitative structure-activity relationships (QSARs) were constructed through the combined application of DFT (density functional theory) and WHIM (weighted holistic invariant molecular) theory. Results from the QSAR analyses suggest that dispersion interaction along the lateral sites of PHDDs should interpret the vast majority of variance of binding affinities as well as the consequent toxicity. Although electrostatic interaction is comparatively less influential, it should not be negligible. Long-range dispersion interaction is also described in QSARs with minute influence. Quadrupole moment tensor perpendicular to the ring plane, i.e., Q(zz) and its implicated electrostatic interaction plays an important role in the contribution to induction potencies.
Gu
Chenggang
C
State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008, PR China; State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, PR China. Electronic address: cggu@issas.ac.cn.
Jiang
Xin
X
State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008, PR China.
Ju
Xuehai
X
Department of Chemistry, Nanjing University of Science and Technology, Nanjing 210094, PR China.
Gong
Xuedong
X
Department of Chemistry, Nanjing University of Science and Technology, Nanjing 210094, PR China.
Wang
Fang
F
State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008, PR China.
Bian
Yongrong
Y
State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008, PR China.
Sun
Cheng
C
State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, PR China.
D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004147:Dioxins / Q000633:toxicity*; D004787:Environmental Pollution; D006841:Hydrocarbons, Aromatic / Q000633:toxicity; D006846:Hydrocarbons, Halogenated / Q000633:toxicity; D008958:Models, Molecular; D008962:Models, Theoretical; D021281:Quantitative Structure-Activity Relationship; D011789:Quantum Theory
D004147:Dioxins; D006841:Hydrocarbons, Aromatic; D006846:Hydrocarbons, Halogenated; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; C020887:dibenzo(1,4)dioxin