Experimental And Molecular Docking Study On The Interactions Between Bisphenol Analogues And Serum Albumins

Bisphenols,a class of chemicals with two hydroxyphenylfunctionalities,have been employed as base chemicals in the manufacture of polycarbonate plastics and epoxy resins.The halogenated derivatives of bisphenol,tetrachlorobisphenol A?TCBPA?and tetrabromobisphenol A?TBBPA?,are commonly used as flame retardants.Along with extensively commercial usages of these bisphenol compounds,many research indicate potential toxicity of human exposure,including acute toxicity,genotoxicity,and endocrine-disrupting activity.In addition,these biologically active chemicals can cross the maternal–fetal placental barrier through blood,the possible impact of bisphenol analogs are hence more problematic for women during the perinatal period.Serum albumins play an important physiological role in the transportation and delivery of various ligands including long-chain fatty acids,porphyrins,bilirubin,steroids,etc.Furthermore,binding of small molecules to serum albumin may have a great influence on the absorption,distribution,metabolism,and excretion of those compounds in the body.The blood levels of bisphenol analogues in mammals are associated with acute toxicity and endocrine-disrupting activity byinfluencing the circulation of compounds and increasing the plasma half-life.The research of the environment pollutant-serum albumin interactions is not only important to explore toxicological mechanism of these compoundsbut is also helpful to provide the relationship between the structures of homologous pollutants and the binding properties to targeting proteins.Because of the similarity of bisphenol chemicals in molecular structure,it is natural tostudy whether they could influence the normal physiological function of proteins.In this work,a comprehensive study of TBBPA,TCBPA,BPS,BPA,BPAFwith HSA and BSA have been conducted by ESI-MS,FS and molecular docking.The results obtained from the three methods are consistent,indicating that the order of binding ability for these compounds interacting with HSA or BSA is:TBBPA>TCBPA>BPS>BPA?BPAF.The stoichiometry of binding was determined by ESI-MS analysis and showed that TBBPA could from 1:1,1:2,1:3 TBBPA-bound HSA complexes,TCBPA formed 1:1 and 1:2 complexes and BPS could only form 1:1 BPS-HSA complex.Very similar observations were obtained for these compounds interacting with BSA but the intensities of the corresponding BSA complexes were lower than those of HSA.The calculated thermodynamic parameters obtained by FS measurementsuggested that hydrogen bonds and electrostatic forces played important roles for these interactions.Binding energies of TBBPA,TCBPA and BPS calculated by molecular docking were-35.18,-34.39 and-25.89 k J·mol^-1,respectively,in good agreement with the FS measurement.By comparing the bindings and stuctures of these bisphenol analogues,we can see that halogenated substitutions on the phenyl rings of bisphenols enhance the binding ability with HSA or BSA,but fluoro-substituent on bridging alkyl moiety has little effect on the binding.Whether or not the toxicities of these bispheols are affected by such substitutions as applied to their binding abilities needs further investigation.Our comprehensive results may provide a better insight into the effects of bisphenol drugs on protein during the blood transportation process.The characterization of binding of bisphenol compounds with serum albumins appears to have significance in relation to further development of drug screening and the toxicity in vivo.