Research On Bioconcentration And Molecule Modification Of Selected Aromatic Compounds Based On 3D-QSAR/HQSAR

Aromatic compounds are a class of compounds with the structure of benzene ring,widely used in a variety of industries,such as fuels,industrial solvents,pharmaceuticals,pesticides and other commodity raw materials.Most aromatic compounds can be enriched in organisms,have high toxicity and carcinogenic effects,and are easy to migrate and difficult to degrade,which can cause serious pollution problems once exposed to the environment.Therefore,this paper studied the bioconcentration of some selected aromatic compounds and designd derivatives with low bioconcentration by combining three-dimensional quantitative structure-activity relationship(3D-QSAR)model and holographic quantitative structure-activity relationship(HQSAR)model.Comparative molecular field analysis(CoMFA)and comparative molecular similarity indices analysis(CoMSIA)of three-dimensional quantitative structure-activity relationship(3D-QSAR)models were conducted using 36 aromatic compound congeners as the training set and 8 aromatic compound congeners as the test set.At the same time,the HQSAR model constructed by HQSAR module in sybyl-x 2.0 software was used to establish the molecular activity substituting site method of coupling HQSAR model activity contribution map and CoMSIA model electrostatic field contour map to influence the bioconcentration of aromatic compounds.The molecular design of low bioconcentration PeCB derivatives was carried out with PeCB as the target molecule.Considered the contour map of CoMSIA model and the activity contribution map of HQSAR model,it was found that the introduction of positive groups at 5-position of PeCB was beneficial to reduce its bioconcentration.Based on this,7 PeCB derivatives with low bioconcentration were designed.The POPs characteristics of 7 PeCB derivatives were evaluated,and 4 derivatives(5-OH-PeCB.5-CH2OH-PeCB,5-NH2-PeCB and 5-CH3-PeCB)were screened out.Their biodegradability increased to a certain extent(less than 10%)with little change in migration and toxicity,and their bioconcentration decreased to a better extent(more than 10%).In addition,the binding effects of pollutants and serum albumin were positively correlated with the bioconcentaration.The mechanism of low bioconcentration of derivatives was studied by selecting 5-CH2OH-PeCB and PeCB combined with Bovine Serum Albumin(BSA).Two molecules docked with BSA protein by molecular docking.The results showed that hydrophobic interactions mainly affected the binding of BSA protein,and 9 amino acid residues participated in the binding of PeCB and BSA protein,providing 22 non-bond interactions;8 amino acid residues in the binding process of 5-CH2OH-PeCB and BSA protein provided 15 non-bond interactions.The binding energy were calculated by molecular dynamics,and the results showed that PeCB had better binding effect with BSA protein,and van der Waals energy mainly affected the binding energy of PeCB and derivative molecules with BSA protein.