Evaluating phospholipid-and protein-water partitioning of two groups of chemicals of emerging concern: Diastereo- and enantioselectivity

摘要

The partitioning between phospholipids/proteins and water can be used to predict the bioaccumulation potential of chemicals with better accuracy compared with n-octanol-water partition coefficient. However, such partitioning is poorly understood for chiral chemicals, many of which exhibit differential bioaccumulation and toxicity potential between enantiomers. In this study, the enantiospecific liposome-water and bovine serum albumin (BSA)-water partition coefficients (Klip/w and KBSA/w, determined at 25 degrees C and 37 degrees C, respectively) were measured by equilibrium dialysis for alpha-, beta-, and gamma-hexabromocyclododecane (HBCD) and three beta-blockers (propranolol, metoprolol, and sotalol). Raman and fluorescence analyses and molecular docking were conducted to provide additional insights into the partitioning process. Results showed alpha- and beta-HBCD displayed stronger enantioselective partitioning to liposomes with the (-)-form, while (-)-alpha-HBCD, R-(+)-pmpranolol, R(+)-metoprolol, and E2-sotalol favored partitioning to BSA compared with their antipodes. Raman spectra revealed alpha- and gamma-HBCD enhanced and reduced the organization of liposome acyl chains, respectively, and polar interactions enhanced the liposome partitioning of beta-blockers. Fluorescence spectra indicated the changed tryptophan microenvironment might influence the BSA steric effect toward HBCD, and electrostatic interactions dominated the formation of BSA-beta-blocker complexes. Molecular docking results supported the difference in the thermodynamic nature of interaction between the studied enantiomers and BSA.

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