Bioaccumulation of PFOS Isomers in Transporter Proteins

The many-decade use of perfluorooctanesulfonic acid (PFOS) in firefighting foams and other products has resulted in their accumulation in water sources and terrestrial environments. Long-term exposure of PFOS has been linked to detrimental effects on human health. PFOS, primarily manufactured through electrochemical fluorination (ECF), yielded both linear and branched isomers. While progress has been made in understanding the health impacts of linear PFOS exposure on human health, there is far less understanding about the toxicological effects and bioaccumulative potential of their branched isomers. In this study, the bioaccumulation potential of linear PFOS and five different branched isomers in the long-chain fatty acid (LCFA) transport protein from Escherichia coli (E. coli) is investigated using molecular dynamics simulations. The bioaccumulative potential of the PFOS isomers was assessed by computing their binding strength at both the low-affinity site and the high-affinity site in comparison with natural ligands. The binding characteristics of PFOS isomers from in silico examinations are in good agreement with in vitro cellular studies. Our study demonstrates a preferential bioaccumulation potential for certain branched isomers rather than linear PFOS. The low hydrogen bonding network of disubstituted isomers compared to monosubstituted isomers at the low-affinity site corroborates with their minimal abundance in the in vitro studies. The interactions between the PFOS isomers with residues ARG_157 and GLU_319 determine their binding potential. Additionally, the location of -CF₃ substitutions in branched PFOS isomers plays a crucial role in governing their overall bioaccumulation potential, providing insight about the bioaccumulation potential in living organisms.