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

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 ℃ and 37 ℃, respectively) were measured by equilibrium dialysis for α-, β-, and γ-hexabromocyclododecane (HBCD) and three β-blockers (propranolol, metoprolol, and sotalol). Raman and fluorescence analyses and molecular docking were conducted to provide additional insights into the partitioning process. Results showed α- and β-HBCD displayed stronger enantioselective partitioning to liposomes with the (–)-form, while (–)-α-HBCD, R-(+)-propranolol, R-(+)-metoprolol, and E2-sotalol favored partitioning to BSA compared with their antipodes. Raman spectra revealed α- and γ-HBCD enhanced and reduced the organization of liposome acyl chains, respectively, and polar interactions enhanced the liposome partitioning of β-blockers. Fluorescence spectra indicated the changed tryptophan microenvironment might influence the BSA steric effect toward HBCD, and electrostatic interactions dominated the formation of BSA−β-blocker complexes. Molecular docking results supported the difference in the thermodynamic nature of interaction between the studied enantiomers and BSA.