No abstract

Legacy perfluoroalkyl substances (PFASs) are known environmental pollutants with serious adverse health effects. Perfluoroethercarboxylic acids (PFECAs), emerging PFASs now being substituted for legacy PFASs, have recently been detected in the environment. Cyclodextrins (CDs) have been proposed as agents for the remediation of problematic pollutants, including legacy PFASs. The current study uses F NMR spectroscopy to measure the complexation of mono-, di-, and triether PFECAs by CDs for eventual environmental applications. Eight PFECAs were characterized byF and C NMR. The change in chemical shift of individual fluorines upon complexation of CDs at various stoichiometric ratios was used to determine the host-guest association constants. All studied PFECAs were most strongly encapsulated by β-CD, with association constants from 10-10 M depending on chain length and number of ether functionalities. F-H heteronuclear Overhauser effect spectroscopy (HOESY) NMR experiments were performed for the β-CD complexes of two branched monoethers, PFPrOPrA ("GenX") and PFDMMOBA, to elucidate the structural details of the complexes, determine the specific orientation, and position of β-CD along the PFAS chain, and assess the roles of hydrogen-bonding and PFECA branching on the host-guest interactions. The results give new understanding into the fundamental nature of the host-guest complex between cyclodextrins and perfluorinated surfactants.

Perfluorooctanoic acid (PFOA), a persistent organic pollutant known to cause adverse health effects, strongly binds to human serum albumin (HSA). β-Cyclodextrin (β-CD), a nontoxic cyclic sugar, strongly complexes PFOA in a host-guest complex and has been proposed for environmental remediation of PFOA. The interactions between HSA, PFOA, and β-CD were investigated in order to determine if β-CD can reverse the binding of PFOA to HSA, with potential therapeutic applications toward exposure to PFOA. F Nuclear magnetic resonance (NMR), circular dichroism, and fluorescence spectroscopies were used to study these interactions. Multiple PFOA binding sites to HSA, one with strong affinity and others with low affinity, are evident from changes in the fluorescence emission spectra of HSA and the fluorescence lifetimes of the single Trp residue in HSA with increasing PFOA concentration. Structural changes in the protein are also evident from changes in the circular dichroism spectra of HSA upon titration of PFOA. Addition of β-CD to PFOA and HSA reversed these changes, indicating that formation of the β-CD:PFOA host-guest complex is favored even in the presence of HSA. Equimolar β-CD to PFOA (1:1 β-CD:PFOA ratio) causes dissociation of the weakly bound PFOA from HSA, whereas excess β-CD relative to PFOA (5:1 β-CD:PFOA ratio) leads to the complete disassociation of the strongly bound PFOA molecule from HSA. TheF NMR studies further suggest that the 2:1 β-CD:PFOA complex inhibits PFOA binding to HSA. These data demonstrate that β-CD has potential to be used in therapeutic applications for PFOA in human blood.

No abstract

Perfluorooctanoic acid (PFOA) has been linked to negative health outcomes including cancer, thyroid disease, infertility, and developmental delays. β-Cyclodextrin (β-CD), a cyclic sugar, has been previously shown to form strong host–guest complexes with PFOA, and is proposed as a means of environmental remediation with respect to this widespread contaminant. In the present study, β-CD was directly examined with regards to possible attenuation of the toxicity of PFOA specifically employing the zebrafish (Danio rerio) embryo model. Zebrafish embryos were exposed to various concentrations of PFOA without β-CD, and with equimolar (1:1) and excess (2:1) molar ratios of β-CD to PFOA, and assessed for lethality and developmental toxicity through seven days post-fertilization (dpf). Rapid onset of lethality with limited morphological abnormalities was observed at relatively low concentrations of PFOA (LC50 ≈ 50 ppm), along with effects on morphometric and neurobehavioral parameters in surviving embryos. A highly significant difference (p < 0.0001) was observed between the 2:1 treatment, and both 1:1 and PFOA only treatments, with respect to lethal concentration and apparent neurobehavioral effects, suggesting an effectively reduced toxicity of the fully complexed PFOA. In contrast, however, neither β-CD treatment reduced developmental toxicity with respect to the morphometric endpoint (i.e., interocular distance). Whereas LC50 of PFOA alone did not change over 7 dpf, the 1:1 and 2:1 values decreased slightly over time, suggesting either delayed or alternative toxic effects on later developmental stages at presumptively lowered levels. This study, therefore, indicates β-CD may be an effective agent to reduce toxicity of and mitigate environmental health concerns associated with PFOA, but that further study is required to elucidate the mechanism of complexation as it relates to the attenuation of toxicity.