Biomimetic Chromatography: A Novel Approach for Measuring Phospholipid Membrane–Water and Protein–Water Partition Coefficients for Target and Suspect PFAS

Physiologically relevant partition coefficients between an aqueous phase (plasma), lipids (cell membrane), and proteins are lacking for many per- and polyfluoroalkyl substances (PFAS). Biomimetic chromatography utilizes immobilized artificial membrane (IAM), human serum albumin (HSA), and alpha-1-glycoprotein (AGP) stationary phases to determine partition coefficients. A rapid-gradient biomimetic approach was used to determine partition coefficients for 81 target PFAS and 37 suspect PFAS in a 3M aqueous film forming foam. PFAS were categorized as acids, bases, or neutrals and used to interpret lipophilic contributions to binding on IAM, HSA, and AGP columns. Partition coefficients on the IAM membrane (log <i>K</i>_IAM: 1.4 to 7.9; median 3.4) and AGP protein (log <i>k</i>_AGP: -1.9 to 0.72; median 0.31) increased linearly with increasing fluorinated chain length, while those for HSA protein (log <i>K</i>_HSA: 0.45 to 5.1; median 4.3) reached a plateau at a specific chain length (∼C6-C8). Zwitterionic PFAS at pH 7.4 exhibited lower affinities for both the IAM membrane and HSA protein, which are likely due to the smaller fraction of the charged species at pH 7.4. The partition coefficients (CHI log <i>D</i> [chromatographic log <i>D</i> derived from the Chromatographic Hydrophobicity Index scaled to the octanol/water partition coefficient, log <i>D</i>]), log <i>K</i>_IAM, log <i>K</i>_HSA, and log <i>k</i>_AGP) expand our understanding of how PFAS behave in the body and provide a foundation for future toxicokinetic modeling.The rapid-gradient approach offers a novel method for measuring partition coefficients for PFAS in complex mixtures.