Research On Molecule Modification And Bioconcentration Of Phenols Based On 3D-QSAR And Molecular Docking

Phenolic compounds are a common chemical raw material,which are widely used in many industries.These compounds can be enriched in an organism and difficult to be biodegraded,migrate in the environment,exhibit relatively strong toxicity,and seriously harm the ecological environment.Therefore,in this paper,bioconcentration of phenolic compounds are studied and phenols derivatives with low bioconcentration are designed through three-dimensional quantitative structure activity relationship(3D-QSAR)and molecule docking.Based on the logarithmic data of bioconcentration factors(logBCF)of 36 phenolic compounds,the 3D-QSAR models were constructed by comparative molecular similarity indices analysis(CoMSIA)and comparative molecular field analysis(CoMFA).At the same time,the logBCF values of 250 phenolic compounds are predicted by these two models.Taking pentachlorophenol(PCP)as an example,the PCP three dimensional isopotential map of the CoMSIA model is analyzed.The results show that both models can predict the logBCF value of phenolic compounds well,and electrostatic field has a great influence on phenolic bioconcentration;The addition of lower electronegativity groups at the R2 and R6 site of PCP significantly reduced the logBCF value of the PCP molecule.In addition,the combination of PCP and superoxide dismutase(SOD)can reduce the accumulation of PCP in organisms,thus its bioconcentration in organisms is reduced.PCP is docked with 8 SOD by molecular docking method,the mechanism of decreasing PCP bioconcentration is analyzed from hydrogen bond interaction and amino acid residues.The results show that the hydrogen bond interaction is the main action to stabilize complex,and the hydrogen bond length is generally less than 3A;9 kinds of amino acids(LYS,GLU,PRO,HIS,ASP,GLY,LEU,ASN and GLN)participate in the formation of hydrogen bond,and hydrophilic amino acids contribute greatly to the stability of the receptor protein-ligand complex.Based on the molecular modification information provided by CoMSIA model and molecular docking method,7 PCP derivatives with low bioconcentration were designed,and their energy barrier for derivative reactions are calculated,as well as their biological activity are predicted.The results show that the order of reaction pathways of 7 PCP derivatives is-SC1>-CH2C1>-COCl>-CC13>-CH=CH2>-NO2>-SH;Combined with the insecticidal effect,migration and anaerobic biodegradability of the designed PCP derivatives,an environmentally-friendly molecule 6-COCl-PCP was screened out.The insecticidal effect of 6-COCl-PCP increased by 1.37%,migration decreased by 0.94%,anaerobic biodegradability increased by 24.81%and bioconcentration decreased by 32.89%;Compared with the objective molecule,the score of 6-COCl-PCP docking with 8 SOD averagely increase by 48.03%,which indicated that the bioconcentration of 6-COCl-PCP is obviously decreased.