Interaction Mechanism Between The Thermal Conversion Products Of Pyrethroid Insecticides And Human Serum Albumin

Pyrethroid insecticides(PIs)are a class of structurally similar non persistent organic pollutants.Because they are broad-spectrum,efficient,and low toxicity,they are widely used.They can be degraded and metabolized into products with similar structures,stronger toxicity,and longer half-lives in food and human bodies.Therefore,the degradation rule of PIs during hot working in vegetables,the toxicity of conversion products and the interaction mechanism between conversion products and human serum albumin(HSA)were studied.The main research contents are as follows:(1)Study on the thermal conversion behavior of PIs in vegetables and identification of their thermal conversion products.Based on the constructed method for simultaneous determination of PIs and their conversion products in vegetables by high performance liquid chromatography(HPLC),the conversion behavior of residual PIs in vegetables during hot working was investigated.The best extraction effect was achieved when the extraction solvent was acetonitrile with 0.1% acetic acid,the ultrasonic extraction time was 15 min,and the purification was 100 mg graphitized carbon black(GCB).The recovery rate was 93%-106%.Crown daisy and Indian lettuce were treated with hot working,and the established HPLC method was used to simultaneously detect PIs and their conversion products.The results showed that the degradation rate of cypermethrin in crown daisy during blanching was 16.87%,cyfluthrin in Indian lettuce was 36.74%.However,3-PBA and 4-F-3PBA were not detected.The degradation rate of cypermethrin in crown daisy during stir frying was 76.76%,cyfluthrin in Indian lettuce was 71.95%,and a small amount of 3-PBA and 4-F-3-PBA were generated,respectively.Based on density functional theory calculation,the conversion pathways of cypermethrin and cyfluthrin were proposed.The conversion products were monitored by UHPLC-MOF/MS,and a total of seven conversion products were detected.Although the processing factor of PIs during hot working was less than 1,the toxicity of their conversion products should also be comprehensively considered.(2)Toxicity prediction of conversion products and simulation of their interaction with HSA.The ADMET characteristics of PIs and four common conversion products were evaluated by computational toxicology.It was found that the conversion products had longer half-life,higher hepatotoxicity and high binding degree with plasma protein.As the most abundant transport protein in plasma,HSA was used as a protein model to simulate the interaction with conversion products through molecular docking and molecular dynamics.The results showed that four conversion products were stably bound to HSA at site I,and the conformational changes of HSA were not significant.Therefore,it is necessary to be cautious about the safety risks and toxicity hazards caused by the residues of PIs and their conversion products in food.(3)Study on the interaction mechanism between PIs conversion products and HSA.Based on the above computer simulation results,the interaction mechanism between PIs conversion products and HSA was explored by multispectral and thermodynamic methods.The interaction between 3-phenoxybenzyl alcohol(3-PBAlc)and HSA was not strong,while 3-PBA,4-F-3-PBA,and 3-(4′-hydroxy)phenoxybenzoic acid(4′-OH-3-PBA)all caused static quenching of HSA.They were spontaneously bound to HSA at site I through van der Waals forces and hydrogen bonds.The binding between 4′-OH-3-PBA and HSA was the strongest,followed by4-F-3-PBA.3-PBA,4-F-3-PBA,and 4′-OH-3-PBA also caused changes in the secondary structure of HSA,significantly increasing the content of α-helix in HSA and enhancing its stability.This may lead to a slower metabolism and excretion rate of conversion products in body,and may also interfere with the transportation of other endogenous substances by HSA,thereby increasing the risk of sustained exposure to PIs conversion products and affecting body health.The degradation of PIs and the formation of their conversion products in hot working of vegetables were systematically studied,and the toxic effects of these conversion products and their interaction mechanism with HSA were further evaluated.This study can provide a reference for the control and toxicity evaluation of PIs and their conversion products residues in food.