Strong associations of short-chain perfluoroalkyl acids with serum albumin and investigation of binding mechanisms

• Published in: Environmental toxicology and chemistry Vol. 30; no. 11; pp. 2423 - 2430
• Main Authors: Bischel, Heather N., MacManus-Spencer, Laura A., Zhang, Chaojie, Luthy, Richard G.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.11.2011; Blackwell Publishing Ltd
• Subjects: Albumin; Animals; Binding sites; Bioaccumulation; Carbon; Carboxylic Acids - chemistry; Carboxylic Acids - metabolism; Cattle; Chemical compounds; Dialysis; Environmental behavior; Fluorescence; Fluorocarbons - chemistry; Fluorocarbons - metabolism; Hydrogen-Ion Concentration; Ionization; Ligands; Mass spectrometry; Modeling; Perfluoroalkyl acids; Protein Binding; Proteins; Serum Albumin, Bovine - chemistry; Serum Albumin, Bovine - metabolism; Spectrometry, Fluorescence; Spectrometry, Mass, Electrospray Ionization; Sulfonates; Tandem Mass Spectrometry; Water distribution
• ISSN: 0730-7268; 1552-8618
• DOI: 10.1002/etc.647

Interactions of perfluoroalkyl acids (PFAAs) with tissue and serum proteins likely contribute to their tissue distribution and bioaccumulation patterns. Protein–water distribution coefficients (KPW) based on ligand associations with bovine serum albumin (BSA) as a model protein were recently proposed as biologically relevant parameters to describe the environmental behavior of PFAAs, yet empirical data on such protein binding behavior are limited. In the present study, associations of perfluoroalkyl carboxylates (PFCAs) with two to 12 carbons (C2–C12) and perfluoroalkyl sulfonates with four to eight carbons (C4, C6, and C8) with BSA are evaluated at low PFAA:albumin mole ratios and various solution conditions using equilibrium dialysis, nanoelectrospray ionization mass spectrometry, and fluorescence spectroscopy. Log KPW values for C4 to C12 PFAAs range from 3.3 to 4.3. Affinity for BSA increases with PFAA hydrophobicity but decreases from the C8 to C12 PFCAs, likely due to steric hindrances associated with longer and more rigid perfluoroalkyl chains. The C4‐sulfonate exhibits increased affinity relative to the equivalent chain‐length PFCA. Fluorescence titrations support evidence that an observed dependence of PFAA‐BSA binding on pH is attributable to conformational changes in the protein. Association constants determined for perfluorobutanesulfonate and perfluoropentanoate with BSA are on the order of those for long‐chain PFAAs (Ka∼106/M), suggesting that physiological implications of strong binding to albumin may be important for short‐chain PFAAs. Environ. Toxicol. Chem. 2011;30:2423–2430. © 2011 SETAC