Noncovalent Interactions of Long-Chain Perfluoroalkyl Acids with Serum Albumin

Preferential distribution of long-chain perfluoroalkyl acids (PFAAs) in the liver, kidney, and blood of organisms highlights the importance of PFAA-protein interactions in PFAA tissue distribution patterns. A serum protein association constant may be a useful parameter to characterize the bioaccumulative potential and in vivo bioavailability of PFAAs. In this work, association constants (K-a) and binding stoichiometries for PFAA-albumin complexes are quantified over a wide range of PFAA: albumin mole ratios. Primary association constants for perfluorooctanoate (PFOA) or perfluorononanoate (PFNA) with the model protein bovine serum albumin (BSA) determined via equilibrium dialysis are on the order of 10(6) M-1 with one to three primary binding sites. PFNA was greater than 99.9% bound to BSA or human serum albumin (HSA) at a physiological PFAA:albumin mole ratio (< 10(-3)) corresponding to a high protein-water distribution coefficient (log K-pw > 4). Nanoelectrospray ionization mass spectrometry (nanoESI-MS) data reveal PFAA-BSA complexes with up to eight occupied binding sites at a 4:1 PFAA:albumin mole ratio. Association constants estimated by nanoESI-MS are on the order of 10(5) M-1 for PFOA and PFNA and 10(4) M-1 for perfluorodecanoate and perfluorooctane-sulfonate. The results reported here suggest binding through specific high affinity interactions at low PFAA:albumin mole ratios.