Prediction Of Acute Toxicity And Aryl Hydrocarbon Receptor Activity For Oxygenated Polycyclic Aromatic Hydrocarbon

Oxygenated polycyclic aromatic hydrocarbons(OPAHs)is a new class of pollutants formed by incomplete combustion of fossil fuels or chemical,photochemical or biological oxidation of PAHs.To date,many OPAHs have been detected in the environment,and some OPAHs have developmental toxicity,mutagenicity and carcinogenicity.However,there are still many OPAHs lacking toxicity data and the mechanism of OPAHs toxicity remains unknown.The quantitative structure-activity relationship(QSAR)can predict the toxicity of OPAHs to reduce the need for expensive,time-consuming and laborious of toxicity testing.Molecular docking can predict the interaction between OPAHs and biomacromolecules.The QSAR model was developed to predict the acute toxicity(log EC₅₀)of OPAHs zebrafish embryos,human aryl hydrocarbon receptor(h AHR)activity in yeast and mouse AHR(m AHR)activity in mouse hepatoma cells.After optimizing the molecular structure,quantum chemical descriptors and Dragon descriptors of 32 types of OPAHs were calculated,and then the QSAR model of zebrafish embryo log EC₅₀(R²=0.781)was established by multiple linear stepwise regression method.It was found that the capacity of electron gain and loss and hydrophobicity of OPAHs were important factors affecting the acute toxicity of OPAHs.The h AHR activities of 30 types of PAHs and OPAHs in yeast and the m AHR activities of 20 PAHs and OPAHs in mouse hepatoma cells were established by the same way.For the model of h AHR activity in yeast(R²=0.880),the hydrophobicity of the molecule was the main factor affecting the h AHR activity.For the model of m AHR activity in mouse hepatoma cells(R²=0.817),molecular polarity was the main factor affecting m AHR activity.The goodness of fit evaluation,internal verification and external verification of the above three QSAR models indicated that the model has good robustness and predictive ability.The application domain of the model is represented by Williams diagram,which shows that the model has good adaptability and ductility.Molecular docking was conducted to explore the interaction forces between PAHs and OPAHs and m AHR.Vina software was used to conduct molecular docking of m AHR protein with PAHs and OPAHs,and the binding energy showed a strong correlation with m AHR activity,that is,the higher binding energy resulted in the higher m AHR activity.Hydrogen bonding and hydrophobic interaction were the main contributions between PAHs,OPAHs and m AHR.