Molecular Modification Of Pentachlorobenzene To Improved Bioconcentration By Multiple Receptors In The Food Chain

Chlorobenzenes were widely present in all walks of life,has strong bioconcentration,can migrate long distances in the environment,is not easily degraded naturally,and is highly toxic,causing serious harm to the ecological environment.Therefore,this article takes the bioconcentration of chlorobenzene organic compounds as the starting point,and successively constructs the traditional CBs bioconcentration 3D-QSAR model and the revised CBs food chain multi-bioreceptor comprehensive bioconcentration 3D-QSAR model.In this way,the molecular modification of chlorobenzene derivatives with significantly reduced bioconcentration and unchanged functional characteristics was made.In this paper,the QSAR module of SYBYL-X 2.0 from Tripos corporation in the United States was adopted to construct the traditional CBs bioconcentration 3D-QSAR and the modified CBS food chain multi-bioreceptor comprehensive bioconcentration 3D-QSAR using(CoMFA)method and(CoMSIA)method,respectively.The results show that the traditional CBs bioconcentration CoMFA model constructed,the cross-check coefficient q2 is 0.980(>0.5),the best main factor N is 7,the non-cross-check coefficient R2 is 1,the r2 pred is 0.975(>0.6),the standard deviation SEE is 0.028.The modified CBs food chain multi-bioreceptor comprehensive bioconcentration CoMFA model,the cross-check coefficient q2 is 0.798(>0.5),the best main factor N is 2,the non-cross-check coefficient R2 is 0.927(>0.8),the r2pred is 0.847(>0.6),the standard deviation SEE is 0.146,which verifies that the constructed models have strong stability functions and good test functions.In the traditional CoMFA model of bioconcentration of chlorobenzene organic compounds,the contribution of S field and E field are 43.20%and 56.80%,respectively;In the revised CoMFA model of multi-bioreceptor comprehensive bioaccumulation of chlorobenzene organic compounds,the contribution of S field and E field are 38.20%and 61.80%,respectively.Analysis of the constructed CoMFA model found that the E field is the most important factor affecting the Kow size of the chlorobenzene molecule.According to the three-dimensional equipotential diagram of the 3D-QSAR model,the pentachlorobenzene molecule is used as the target molecule to design a pentachlorobenzene derivative molecule with low bioconcentration.The biomagnification effect of derivatives in food chain organisms is slowed down,the migration ability is reduced,the toxicity is reduced,and the degradability is improved.At the same time,its functional properties-flame retardancy and insulation are basically unchanged.Based on 2D-QSAR,molecular docking technology and biological metabolic pathway simulation,the bioconcentration mechanism of CBs was analyzed.It was found that the decrease of bioconcentration of derivatives was caused by the enhancement of molecular energy interaction mode and the change of molecular dipole moment and energy gap value interaction mode.When the chlorobenzene molecule binds to the degrading enzyme,the number of hydrophobic amino acid residues around the derivative molecule is significantly higher than that of the target molecule,which is conducive to the binding of the molecule to the degrading enzyme.Based on molecular biological metabolic pathway simulation and inference,by calculating the metabolic pathway energy barrier,it can be obtained that the derivative metabolic pathway energy barrier is low.It can indirectly explain the reason why the bioconcentration of pentachlorobenzene derivatives is significantly reduced after modification,which provides a basic theoretical basis for the design of environmentally friendly pentachlorobenzene molecules.