Studies On Biological Effects And Structureactivity Relationship Of Bisphenol A And Its Analogues

Bisphenol A is a reactive monomer in plastic preparation process,which makes it widely used in industrial production.However,in 2008,Canada publicly declared it a toxic chemical and banned the addition of BPA in the preparation of baby bottles.Products prepared with bisphenol A have unique advantages.Therefore,attempts have been made to replace bisphenol A with substances similar in structure and function,but the safety of these substitutes remains to be further studied.Proteins and DNA play important roles in living organisms.In the study of toxicology and pharmacology,proteins and DNA are regarded as important transport carriers and action targets of drugs,and are often used as in vitro biological models to study the pharmacological efficacy and biological activity of drugs.Therefore,it is a very important work to study the interaction between BPA and its derivatives with proteins and DNA,and to explore the influence of its structure on the mechanism,strength and structure-activity relationship of its interaction with biological macromolecules,which can provide a theoretical basis for the research and development of less toxic or non-toxic alternatives to BPA.In this paper,three kinds of bisphenol compounds with different structures were selected to study their interaction with proteins and DNA by various methods,aiming to study the influence of the structure of bisphenol compounds on their interaction with proteins and DNA from different aspects.This paper is divided into five chapters,the specific research content is as follows:Chapter 1:The structure,development history and research status of bisphenol compounds are introduced.The structure and function of serum albumin and DNA were introduced in detail.The research methods of interaction between drugs and biomacromolecules are summarized.Clear the topic selection of the train of thought and research characteristics.Chapter 2:The interaction of bisphenol A,bisphenol F and bisphenol AF with bovine serum albumin(BSA)was studied by various methods.The endogenous fluorescence quenching mechanism of bisphenol compounds on BSA was studied by UV-vis absorption spectra and transient fluorescence spectra.Steady-state fluorescence and gel electrophoresis were used to study the difference of interaction intensity between three bisphenol compounds and BSA.The action sites of bisphenol compounds on BSA were studied by site competition and molecular docking.The effects of bisphenol compounds on the structure of BSA were studied by 3-D fluorescence,synchronous fluorescence,circular dichroism and Fourier transform infrared spectroscopy.Finally,the effects of the structure of bisphenol compounds on the interaction mechanism,strength,position and conformation of bisphenol compounds with BSA were summarized.Chapter 3:The interaction of bisphenol A,bisphenol F and bisphenol AF with human serum albumin(HSA)was studied by various methods.The quenching mechanism of endogenous fluorescence of bisphenol compounds on HSA was studied by variable temperature fluorescence titration.The quenching constant,binding constant and thermodynamic parameters were further calculated,and the main interaction between the three bisphenol compounds and HSA was obtained.The binding sites of bisphenol compounds on HSA were studied by site competition and molecular docking.The effects of bisphenol compounds on the structure of HSA were studied by three dimensional fluorescence,synchronous fluorescence,UV-Vis absorption spectra and Fourier transform infrared spectroscopy.Finally,the effects of the structure of bisphenol compounds on the interaction mechanism,strength,position and conformation of bisphenol compounds with HSA were summarized.Chapter 4:The interaction of bisphenol A,bisphenol F and bisphenol AF with ctDNA was studied.The interaction mechanism of bisphenol compounds with ctDNA was studied by UV-vis absorption spectroscopy,I~-quenching and molecular docking.Fluorescence spectroscopy,gel electrophoresis and electrochemical methods were used to study the difference of the interaction intensity between three bisphenol compounds and ctDNA.Finally,the effects of the structure of bisphenol compounds on the interaction mechanism and intensity of bisphenol compounds with ctDNA were summarized.Chapter 5:This paper is summarized,and the future research on the interaction between bisphenol compounds and biomacromolecules is prospected.