The Chiral Characteristics,Exposure In The Breast Milk And Biometabolic Mechanism Of Polychlorinated Biphenyls

Polychlorinated biphenyls(PCBs)are persistent lipophilic organic pollutants,which possesses the features of environmental stability,biological accumulation and long-distance migration.Breast milks served as the main dietary source of infants are rich in fat,protein and other nutrients.Lipophilic PCBs can be transmitted to infants through the dietary exposure,resulting in negative health risks.There are 19 PCBs can keep configuration stable at room temperature among 209 aromatic congeners.Racemic chiral PCBs may exhibit different behaviors and tendencies in the environment.Enantiomeric fractions(EFs)can be used to determine the selectivity of enantiomers in a reaction environment.At present,studies on chiral PCBs are still at adolescent stage,such as immature preparation and resolution conditions,which lead to high acquisition cost of enantiomer standard samples,thus hindering subsequent studies.Therefore,methods for the separation,characterization and stability of chiral enantiomers should be established to analyze the concentration exposure level of PCBs in breast milk and its enantiomeric characteristics for further health risk assessment.Besides,the degradation mechanism of cytochrome P450(CYP 450)on metabolites of polychlorinated biphenyl ethers could also be considered by density functional theory(DFT)at molecular level,providing theoretical basis for health risk assessment of PCBs exposure and metabolism.The main research contents are as follows:(1)We studied 4 chiral PCBs at room temperature.The analytical and semi-preparative high-performance liquid chromatography(HPLC)were used for the separation and collection of high purity enantiomers.Target PCBs were completely separated,and the collection time was short for operation.Characterization of the absolute configurations of PCB 45,95,136,and 149 was conducted with a combination of theoretical and experimental electronic circular dichroism measurements.A well-established methodology of collection and configuration identification for analogous PCB derivatives was built.(2)Four chiral PCBs enantiomer monomers obtained from the above experiments were used to analyze the configuration stability of chiral PCBs under different solvent and temperature conditions.During the process of detection,configurations of chiral PCBs were not affected by solvents,but affected by GC inlet temperature.With the validation of rice samples exposed to PCB 95,it was demonstrated that the effect of biological processes with enantioselectivity on EF was underestimated.Computational simulations were conducted to correct the deviation of EFs through Arrhenius fitting equation.With the supplementary of rotational activation energy for 19 chiral PCBs,we could better understand and predict the configuration stability of 19 chiral PCBs.(3)A multi-center study with biological individual monitoring method was conducted to analyze the concentration of PCBs in breast milk from Mianyang,Wuhan and Hangzhou.The age and source of drinking water were considered to be two major factors which influence the exposure of PCBs in human breast milk.The total load level of PCBs in breast milk were related to the pollution background value and the urban development level in different regions.Chiral PCB 95,PCB 136 and PCB 149 in breast milk samples distributed with the characteristics of enantiomeric selective during the environmental process.(4)Typical triclosan(TCS)was used as the model of biphenyl ether compound for discussion of metabolic mechanism of P450 at molecular level.Hydrogen abstraction was proposed as the decisive step for the reaction rate of metabolic process between Cpd I and TCS.The metabolic radical intermediate from TCS could turn into hydroxylated products by·OH rebound at double state.At quadruple state,due to the existence of reaction energy barrier,·OH could not rebound,so the intermediate would finally act as product with long life cycle.It was proved that free radicals could be coupled by spin distribution.The ionization potential could be used to predict the rebound energy barrier(including biphenyl ether,phenol,antibiotics).