Polyfluoroalkyl substances (PFASs), also known as “forever chemicals”, are man-made chemicals consisting of C-chains, either poly- or per-fluorinated. PFASs have long been detected in the environment, but recent studies found their presence in the human body too. Due to the stable C-F bonds, these compounds resist degradation, and the long-term effects and toxicity on the human body are still unknown. In humans, PFASs have been associated with xenobiotic metabolism, immunity, hepatic steatosis, kidney cancer, liver toxicity, and more. Moreover, PFASs have been detected in the human brain, and it’s hypothesized their potential interference with neurotransmitter synthesis and act as receptor-binding site competitors, potentially leading to cognitive and developmental dysfunctions. However, the mechanism by which these chemicals enter the brain and can cross or bypass the blood-brain barrier transporters is still unclear. Thus, in this study, we aim to conduct a systematic study of PFASs and their binding into some of the known target proteins using computational chemistry tools, including cheminformatics, quantum chemical computation, and molecular docking. The presentation will document the absolute hardnesses, absolute electronegativities, and binding affinities to some known targets in our body, including human serum albumin, liver fatty acid binding proteins, organic anion-transporting polypeptides, and dopamine transporter.
