Binding Of Perfluorooctanoic Acid Research Articles

Perfluorooctanoic acid-contaminated wastewater treatment by forward osmosis: Performance analysis

Perfluorooctanoic acid (PFOA) is a persistent compound, raising considerable global apprehension due to its resistance to breakdown and detrimental impacts on human health and aquatic environments. Pressure-driven membrane technologies treating PFAS-contaminated water are expensive and prone to fouling. This study presented a parametric investigation of the effectiveness of cellulose triacetate membrane in the forward osmosis (FO) membrane for removing PFOA from an aqueous solution. The study examined the influence of membrane orientation modes, feed pH, draw solution composition and concentration, and PFOA concentration on the performance of FO. The experimental results demonstrated that PFOA rejection was 99 % with MgCl2 and slightly >98 % with NaCl draw solutions due to the mechanism of PFOA binding to the membrane surface through Mg2+ ions. This finding highlights the crucial role of the draw solution's composition in PFOA treatment. Laboratory results revealed that membrane rejection of PFOA was 99 % at neutral and acidic pH levels but decreased to 95 % in an alkaline solution at pH 9. The decrease in membrane rejection is attributed to the dissociation of the membrane's functional groups, consequently causing pore swelling. The results were confirmed by calculating the average pore radius of the CTA membrane, which increased from 27.94 nm at pH 5 to 30.70 nm at pH 9. Also, variations in the PFOA concentration from 5 to 100 mg/L did not significantly impact the membrane rejection, indicating the process's capability to handle a wide range of PFOA concentrations. When seawater was the draw solution, the FO membrane rejected 99 % of PFOA concentrations ranging from 5 mg/L to 100 mg/L. The CTA FO treating PFOA-contaminated wastewater from soil remediation achieved a 90 % recovery rate and water flux recovery of 96.5 % after cleaning with DI water at 40 °C, followed by osmotic backwash. The results suggest the potential of using abundant and cost-effective natural solutions in the FO process, all without evident membrane fouling.

An Atomic and Molecular Insight into How PFOA Reduces α-Helicity, Compromises Substrate Binding, and Creates Binding Pockets in a Model Globular Protein.

Per- and polyfluoroalkyl substances (PFAS) pose significant health risks due to their widespread presence in various environmental and biological matrices. However, the molecular-level mechanisms underlying the interactions between PFAS and biological constituents, including proteins, carbohydrates, lipids, and DNA, remain poorly understood. Here, we investigate the interactions between a legacy PFAS, viz. perfluorooctanoic acid (PFOA), and the milk protein β-lactoglobulin (BLG) obtained using a combination of experimental and computational techniques. Circular dichroism studies reveal that PFOA perturbs the secondary structure of BLG, by driving a dose-dependent loss of α-helicity and alterations in its β-sheet content. Furthermore, exposure of the protein to PFOA attenuates the on-rate constant for the binding of the hydrophobic probe 8-anilino-1-naphthalene sulfonic acid (ANS), suggesting potential functional impairment of BLG by PFOA. Steered molecular dynamics and umbrella sampling calculations reveal that PFOA binding leads to the formation of an energetically favorable novel binding pocket within the protein, when residues 129-142 are steered to unfold from their initial α-helical structure, wherein a host of intermolecular interactions between PFOA and BLG's residues serve to insert the PFOA into the region between the unfolded helix and beta-sheets. Together, the data provide a novel understanding of the atomic and molecular mechanism(s) by which PFAS modulates structure and function in a globular protein, leading to a beginning of our understanding of altered biological outcomes.

A structural basis for the activation of peroxisome proliferator-activated receptor gamma (PPARγ) by perfluorooctanoic acid (PFOA)

Perfluorooctanoic acid (PFOA) is a widespread environmental pollutant of the perfluoroalkyl substance (PFAS) class that is extremely resistant to environmental and metabolic degradation, leading to bioaccumulation. PFOA exposure has been linked to many health effects including endocrine disruption and metabolic dysregulation, but our understanding of the molecular mechanisms resulting in these outcomes remains incomplete. One target affected by PFOA is the ligand regulated nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) which plays a critical role in controlling metabolic homeostasis through regulating processes such as adipogenesis, glucose homeostasis, inflammation and osteogenesis. It has been previously established that PFOA activates PPARγ through binding to the PPARγ ligand binding domain (PPARγ LBD) leading to increased expression of PPARγ controlled target genes. However, the mechanism by which PFOA achieves this has remained elusive. Here, we employed a combination of X-ray crystallography and fluorescence polarization assays to provide a structural basis for PFOA mediated activation of PPARγ via binding to the PPARγ LBD. Using X-ray crystallography, the cocrystal structure of the PPARγ LBD:PFOA complex was solved. This revealed that PFOA occupies three distinct sites, two within the PPARγ LBD and one within the activation function 2 (AF2) on the protein surface. Structural comparison of PFOA binding with previously reported PPARγ:ligand complexes supports that PFOA activates PPARγ by a partial agonist mechanism at micromolar concentrations. Fluorescence polarization assays also revealed that PFOA binding to the AF2 is unlikely to occur in a cellular context and confirmed that PFOA behaves as a partial agonist in vitro, weakly recruiting a coactivator peptide to the AF2 of the PPARγ LBD. This discovery provides an advancement in understanding PFOA mediated regulation of PPARγ, giving new insight regarding regulation of PPARγ by PFAS and PFAS substitutes in general and can be applied to the design and assessment of safer PFAS.

Globin X: A target for surfactant-like molecules.

Globin X (GbX) is recognized as a novel, intrinsically hexacoordinate, member of the vertebrate globin family. Previously we showed that GbX is significantly more stable than pentacoordinate vertebrate globins (Hb and Mb) at elevated temperatures, acidic pH as well as in the presence of denaturants. Such a unique feature of this protein led us to examine how the GbX interacts with surfactant-like molecules such as perfluorooctanoic acid (PFOA) and sodium dodecyl sulfate (SDS). In addition to GbXWT protein, the effect of intraprotein disulfide bridge and the heme iron pentacordination on GbX interactions with surfactant-like molecules was investigated by characterizing the GbXC65A and GXH90V constructs. The impact of surfactant on the structural properties of GbX was evaluated based on changes in the Soret band region and the emission properties of intrinsic Trp residues. The Kd values for SDS binding to the deoxy form of GbXWT, GbXC65A, and GbXH90V were determined to be 251 ± 4 μM, 188 ± 7 μM, and 358 ± 91 μM respectively, indicating that the intramolecular disulfide bond and hexacoordination do not have a significant effect on the surfactant-protein complex. However, the met form of GbXWT and GbXC65A binds SDS with Kd of 1426 ± 224 μM and 2106 ± 26 μM, pointing towards a lower affinity of the met form of the protein for SDS surfactant. Interestingly, PFOA produces a minimal change in the Soret band region, suggesting a distinct mechanism of binding. Based on the Trp emission data, the Kd values for PFOA binding to the met form of the protein were determined to be 40 ± 28 μM for GbX WT and 25 ± 1 μM for GbXC65A. The molecular mechanism of surfactant-like molecules binding to GbX was also evaluated using molecular dynamic simulations.

Detail study on the interaction between perfluorooctanoic acid (PFOA) with human hemoglobin (Hb)

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are often referred to as legacy perfluoroalkyl substances (PFAS). Human exposure to PFAS leads to severe negative health impacts including cancers, infertility, and dysfunction in the kidneys. Steady-state absorbance, fluorescence, and circular dichroism (CD) methods were used to study the interactions between PFOA and Hb. The results demonstrate the presence of multiple PFOA binding sites on the Hb protein. The detailed analysis of the ferric hemoglobin protein (met Hb) absorbance data as a function of PFOA concentration indicates the presence of at least two binding sites with equilibrium dissociation constants of 0.8 ± (0.2) × 10−6 M and 63 ± (15) × 10−5 M. A competitive binding study with 1,8-ANS showed PFOA can bind to the same binding site as 1,8-ANS on the Hb protein. The titration curve for PFOA binding to Hb in its CO bound form (CO-Hb) yields a single equilibrium dissociation constant of 139 ± (20) × 10−6 M. PFOA binding at low concentrations occurs at the high-affinity sites leading to the destabilization of the protein structure as reflected by changes in the CD spectrum. PFOA interactions with Hb also interfere with the kinetics of CO association to this protein. The rate for CO association to Hb increases at low PFOA concentrations, whereas at elevated PFOA concentrations, the ligand association is biphasic as a new kinetic process with a different rate constant was observed. Overall, this study provides a detailed explanation of PFOA-induced structural and conformational changes to the Hb protein based on the spectroscopy data.

Thermoresponsive Cationic Polymers: PFAS Binding Performance under Variable pH, Temperature and Comonomer Composition.

The versatility and unique qualities of thermoresponsive polymeric systems have led to the application of these materials in a multitude of fields. One such field that can significantly benefit from the use of innovative, smart materials is environmental remediation. Of particular significance, multifunctional poly(N-isopropylacrylamide) (PNIPAAm) systems based on PNIPAAm copolymerized with various cationic comonomers have the opportunity to target and attract negatively charged pollutants such as perfluorooctanoic acid (PFOA). The thermoresponsive cationic PNIPAAm systems developed in this work were functionalized with cationic monomers N-[3-(dimethylamino)propyl]acrylamide (DMAPA) and (3-acrylamidopropyl)trimethylammonium chloride (DMAPAQ). The polymers were examined for swelling capacity behavior and PFOA binding potential when exposed to aqueous environments with varying pH and temperature. Comonomer loading percentages had the most significant effect on polymer swelling behavior and temperature responsiveness as compared to aqueous pH. PFOA removal efficiency was greatly improved with the addition of DMAPA and DMAPAQ monomers. Aqueous pH and buffer selection were important factors when examining binding potential of the polymers, as buffered aqueous environments altered polymer PFOA removal quite drastically. The role of temperature on binding potential was not as expected and had no discernible effect on the ability of DMAPAQ polymers to remove PFOA. Overall, the cationic systems show interesting swelling behavior and significant PFOA removal results that can be explored further for potential environmental remediation applications.

Montmorillonite clay-based sorbents decrease the bioavailability of per- and polyfluoroalkyl substances (PFAS) from soil and their translocation to plants

Consumption of food and water contaminated with per- and polyfluoroalkyl substances (PFAS) presents a significant risk for human exposure. There is limited data on high affinity sorbents that can be used to reduce the bioavailability of PFAS from soil and translocation to plants and garden produce. To address this need, montmorillonite clay was amended with the nutrients carnitine and choline to increase the hydrophobicity of the sorbent and the interlayer spacing. In this study, the binding of PFOA (perfluorooctanoic acid) and PFOS (perfluorooctanesulfonic acid) to parent and amended clays was characterized. Isothermal analyses were conducted at pH 7 and ambient temperature to simulate environmentally-relevant conditions. The data for all tested sorbents fit the Langmuir model indicating saturable binding sites with high capacities and affinities under neutral conditions. Amended montmorillonite clays had increased capacities for PFOA and PFOS (0.51–0.71 mol kg−1) compared to the parent clay (0.37–0.49 mol kg−1). Molecular dynamics (MD) simulations suggested that hydrophobic and electrostatic interactions at the terminal fluorinated carbon chains of PFAS compounds were major modes of surface interaction. The safety and efficacy of the clays were confirmed in a living organism (Lemna minor), where clays (at 0.1% inclusion) allowed for increased growth compared to PFOA and PFOS controls (p ≤ 0.01). Importantly, soil studies showed that 2% sorbent inclusion could significantly reduce PFAS bioavailability from soil (up to 74%). Studies in plants demonstrated that inclusion of 2% sorbent significantly reduced PFAS residues in cucumber plants (p ≤ 0.05). These results suggest that nutrient-amended clays could be included in soil to decrease PFAS bioavailability and translocation of PFAS to plants.

Nanopore sensing of γ-cyclodextrin induced host-guest interaction to reverse the binding of perfluorooctanoic acid to human serum albumin.

Perfluorooctanoic acid (PFOA) has been one of the most common perfluorochemicals, which are globally pervasive contaminants that are persistent, bioaccumulative, toxic, and have adverse impacts on human health. The highest concentration of PFOA occurs in the blood, where it strongly binds to human serum albumins (HSA). Thus, a method to reverse the HSA-PFOA binding is critical to help facilitate the faster elimination of PFOA from the body to minimize its toxicological effects. Inspired by the remediation effect of cyclodextrin (CD) to PFOA through host-guest interactions, herein, by elucidating inter-molecular interactions using a nanopore sensor, we demonstrated in vitro reversal of the binding of PFOA to HSA using γ-cyclodextrin (γ-CD). The competition behavior for the complexation of PFOA between HSA and γ-CD was discussed in combination with in situ nanopore current recording and nuclear magnetic resonance (NMR) characterization. The present work not only demonstrates the potential therapeutic application of γ-CD for PFOA removal from human blood, but also provides an emerging method for investigating interactions between organic compounds and proteins.

An investigation into the long-term binding and uptake of PFOS, PFOA and PFHxS in soil – plant systems

This study investigated the potential aging and plant bioaccumulation of three perfluoroalkyl acids (PFAAs), perfluorosulphonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexanesulphonic acid (PFHxS) in 20 soils over a six-month period. Sorption coefficients (Log Kd) ranged from 0.13–1.28 for PFHxS, 0.17–1.06 for PFOA and 0.98–2.03 for PFOS, respectively, and bioaccumulation factors (Log BAFs) ranged from 0.29–1.24, 0.22–1.46 and 0.05–0.65 for PFHxS, PFOA and PFOS, respectively. Over the six-month period, Kd values significantly increased for PFHxS and PFOA but the magnitude of the increase was very small and did not translate into differences in plant PFAA-concentrations between aged and freshly spiked treatments. The Kd and BAF values were modelled by multiple linear regression (MLR) to soil physico-chemical properties and by partial least squares regression to soil spectra acquired by mid-infrared spectroscopy (DRIFT−PLSR). Modelling of each PFAA was influenced by different soil properties, including organic carbon, pH, CEC, exchangeable cations (Ca2+, Mg2+, Na+ and K+) and oxalate extractable Al. BAF values were not strongly correlated to any soil property but were inversely correlated to Kd values. Our results indicate that limited aging occurred in these soils over the six-month period.

Amorphous Pd-Loaded Ti4O7 Electrode for Direct Anodic Destruction of Perfluorooctanoic Acid.

We here present a novel Ti4O7-based electrode loaded with amorphous Pd clusters that achieve efficient anodic destruction of perfluorooctanoic acid (PFOA), a persistent water pollutant with significant environmental and human health concerns. These amorphous Pd clusters were characterized by the disordered, noncrystalline arrangement of Pd single atoms in close proximity, in contrast to crystalline Pd nanoparticles that have been often employed to tailor the electronic properties of an electrode. We found that the Ti4O7 electrode loaded with amorphous Pd clusters significantly outperformed the Ti4O7 electrode loaded with crystalline Pd particles due to enhanced electron transfer through dominant Pd-O bonds. Combined with the efficient binding of PFOA and its degradation intermediates to the fluorinated electrode surface, this electrode was capable of mineralizing PFOA and releasing fluoride as F-. The reaction pathway was found to proceed without involving reactive oxygen species and therefore was not quenched by common anions in complex natural water systems such as chloride ions.

Effect of perfluorooctanoic acid on microbial activity in wheat soil under different fertilization conditions

Perfluorooctanoic acid (PFOA) is an emerging persistent organic pollutant which has been identified at significant levels in soils. Existed ecotoxicological studies have mainly employed earthworms to evaluate the toxicity of PFOA. However, little information do we know about the toxicity of PFOA regarding soil microorganisms. Accordingly, the adverse effects of PFOA on microbial activity in a wheat soil under four fertilization treatments were investigated in this study. The microcalorimetric results revealed that the toxicity of PFOA on soil microbial activity in four treatments followed a descending sequence: Control (no fertilization), NK (no P fertilizer, but N and K fertilizers were used), PK (no N fertilizer, but P and K fertilizers were used), and NPK (N, P and K fertilizers were used). The soil sample with higher available P content had higher resistant to PFOA. There were significant differences in urease activity and alkaline phosphatase activity among the four fertilization treated soils. Molecular modeling studies clearly demonstrated that the binding of PFOA with alkaline phosphatase was more stable than with urease through electrostatic interaction, van der Waals force, and hydrogen bonds. These results are expected to provide more comprehensive information in toxicity of PFOA in soil environment.

Fetal bovine serum attenuating perfluorooctanoic acid-inducing toxicity to multiple human cell lines via albumin binding

Perfluorooctanoic acid (PFOA), as a typical emerging organic pollutant, can interact with serum albumin. However, it remains to characterize the binding of PFOA with serum albumin and to address the role of this interaction in related toxic effects. We aimed to characterize the interaction between PFOA and albumin for understanding the effects of this interaction on the uptake, distribution, and toxicity of PFOA in human cells. The results showed that viable cell count was significantly enhanced by addition of fetabl bovine serum (FBS) into cell culture medium with 300 μM PFOA treatment. PFOA mainly existed as complexed with FBS, at FBS concentration > 10%, which substantially reduced the absorption efficiency of all cell lines to PFOA. The majority of PFOA was accumulated in the cytosolic fraction, followed by nuclei, and mitochondria. Conclusively, our study suggests that the complexation of organic contaminants with proteins might mitigate their toxicity by reducing cellular uptake.

Investigating the interaction between three perfluorinated carboxylic acids and the G protein-coupled estrogen receptor: spectroscopic analyses and computational simulations.

In this paper, perfluorinated compounds (PFCs), such as perfluorobutyric acid (PFBA), perfluorooctanoic acid (PFOA) and perfluorododecanoic acid (PFDoA), were selected as typical representatives of perfluorinated carboxylic acids (PFCAs) to study the effects of PFCAs on the G protein-coupled estrogen receptor (GPER). The interaction mechanism of the three types of PFCAs with the GPER was investigated using steady-state fluorescence spectroscopy, ultraviolet-visible spectroscopy, three-dimensional fluorescence spectroscopy, and Fourier transform infrared spectroscopy combined with molecular docking and molecular dynamics simulations. Among these techniques, steady-state fluorescence and ultraviolet-visible spectroscopic analyses showed that PFBA, PFOA and PFDoA quenched the endogenous GPER fluorescence by combined dynamic and static quenching and non-radiative energy transfer. The binding constants (Ka) of PFCAs on the GPER were all larger than 105 L mol-1, indicating that their affinity for the GPER was strong. Fourier transform infrared spectroscopy and three-dimensional fluorescence showed that the secondary structure of the GPER changed after binding to PFCAs. Thermodynamic analysis showed ΔG < 0, which indicated that the interaction between the GPER and PFCAs was spontaneous. For the binding of PFBA and PFOA to the GPER, ΔH > 0 and ΔS > 0, indicating that the interaction was mainly driven by hydrophobic forces; for the binding of PFDoA to the GPER, ΔH < 0 and ΔS < 0, suggesting that van der Waals force and hydrogen bonding were the main interaction forces. Molecular dynamics simulations suggested that the stability of the GPER-PFCA complexes was higher than that of the free GPER, and also that the structure and hydrophobicity of the GPER changed after binding to PFCAs. Molecular docking analysis showed that all three PFCAs could form hydrogen bonds with the GPER, which improved the stability of the complex.

Protonation state effects of estrogen receptor α on the recognition mechanisms by perfluorooctanoic acid and perfluorooctane sulfonate: A computational study

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been reported to cause adverse health effects on wildlife as well as humans. Numerous studies demonstrated that PFOA and PFOS could interfere with the transcriptional activation of estrogen receptor α (ERα) by mimicking the function of endogenous ligand, whereas some reports suggested that the two compounds present non-estrogenic activities. These conflicting results bring a confusion to understand their molecular mechanism on the ERα-mediated signaling pathway. To address this issue, we performed the molecular docking and molecular dynamics simulations to elaborate the structural characteristics for the binding of PFOA and PFOS to ERα. Our results indicated that the two opposite binding orientations were modulated by the protonation states of key residue His524. In sub-acidic condition, PFOA and PFOS prefer to form the H-bonding interactions with the protonated His524, whereas Arg394 provided the H-bonding interactions for stable binding in sub-alkaline condition. Conformational analyses implied that the diverse binding modes were closely related to the conformational propensity of ERα for subsequent coactivator recruitment and transcription activation. Generally, our findings provide a flexible strategy to assess the pH impacts of microenvironment on the toxicities of perfluoroalkyl acids by their interactions with proteins.

β-Cyclodextrin Reverses Binding of Perfluorooctanoic Acid to Human Serum Albumin

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. 19F 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. The 19F 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.

Interactions of perfluorooctanoic acid and perfluorooctanesulfonic acid with serum albumins by native mass spectrometry, fluorescence and molecular docking

The binding information of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) with bovine and human serum albumins was investigated and characterized in details by using a combination method of electrospray ionization mass spectrometry (ESI-MS), fluorescence, circular dichroism (CD) and molecular docking (MD). The ESI-MS analysis revealed that maximally eight PFOA or PFOS molecules could bind to serum albumins at high mole ratios of PFOA/PFOS. Association constants were measured by ESI-MS and suggested that PFOS had a better binding affinity than PFOA. PFOA and PFOS were likely to bind with serum albumins in more than one pocket. The CD data demonstrated that binding of PFOA and PFOS could change the conformation of serum albumins with decreasing α-helix content, which may affect the protein physiological function. The phenomenon of protein fluorescence quenching by the binding of PFOA and PFOS indicated that the hydrophobic pocket proximate to Trp 214 in human serum albumin might be one of the dominated binding sites. This assumption was further confirmed by MD simulation. Consistent to ESI-MS observation, MD results also displayed a stronger binding affinity of PFOS than PFOA according to the calculated binding free energy, which is probably ascribed to one more hydrogen bond formed in the PFOS-bound protein complexes.

Systematic investigation of the toxic mechanism of PFOA and PFOS on bovine serum albumin by spectroscopic and molecular modeling

Perfluorinated compounds (PFCs), an emerging class of globally environmental contaminations, pose a great threat to humans with wide exposure from food and other potential sources. The effects of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) on bovine serum albumin (BSA) under normal physiological conditions were characterized by fluorescence, UV–Vis absorption, Fourier transform infrared (FT-IR) spectroscopy and molecular docking methods. The fluorescence study suggested that the fluorescence quenching of BSA by PFCs was a static procedure forming a PFCs–BSA complex. The negative values of enthalpy change (ΔH) and entropy change (ΔS) indicated that van der Waals forces and hydrogen bonds were the dominant intermolecular forces in the binding of PFCs to BSA. The displacement experiments of site markers and molecular docking revealed that the binding of PFOA to BSA took place in sub-domain IIA (Sudlow site I) whereas PFOS was mainly located in the sub-domain IIIA (Sudlow site II) and partially bound into site I. Furthermore, the results of UV–Vis and FT-IR spectra demonstrated that the microenvironment and the secondary structure of BSA were changed in the presence of PFCs. These results indicated that PFCs indeed impact the conformation of BSA and PFOS was more toxic than PFOA, which were supported by theoretical molecular modeling methods.

Sorption of a branched nonylphenol and perfluorooctanoic acid on Yangtze River sediments and their model components

Many metabolites of organic surfactants such as nonylphenol (NP) and perfluorooctanoic acid (PFOA) are ubiquitously found in the environment and are toxic if not sorbed on soils and sediments. In this study, we quantified the sorption of the NP isomer with the highest endocrine activity, [4-(1-ethyl-1,3-dimethylpentyl) phenol] (NP111), and that of PFOA on Yangtze River sediments and its model components illite, goethite and natural organic matter. The sorption experiments were performed with (14)C-labeled NP111 and PFOA by batch or dialysis techniques. The results showed that the sorption isotherms of NP111 and PFOA on the sediments were fitted well by the linear adsorption model. The sorption of NP111 depended largely on the organic carbon content of the sediments. The K(OC) values of NP111 ranged from 6 × 10(3) to 1.1 × 10(4) L kg(-1) indicating that hydrophobic interaction between NP and organic carbon is the main mechanism of sorption. The sorption of NP111 on illite was poor. The sorption of PFOA on the sediments was significantly lower than that of NP111. The affinity of PFOA to adsorb on goethite was slightly higher than on the sediments, but was moderate on illite and negligible on a reference natural organic matter. Principal axis component analysis confirmed that various sediment parameters control the binding of PFOA. This analysis grouped the respective K(d) values to the contents of black carbon, iron oxides and clay, and, hence, to the specific surface area of the sediments.

Determination of Energies and Sites of Binding of PFOA and PFOS to Human Serum Albumin

Structure and energies of the binding sites of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) to human serum albumin (HSA) were determined through molecular modeling. The calculations consisted of a compound approach based on docking, followed by molecular dynamics simulations and by the estimation of the free binding energies adopting WHAM-umbrella sampling and semiempirical methodologies. The binding sites so determined are common either to known HSA fatty acids sites or to other HSA sites known to bind to pharmaceutical compounds such as warfarin, thyroxine, indole, and benzodiazepin. Among the PFOA binding sites, five have interaction energies in excess of -6 kcal/mol, which become nine for PFOS. The calculated binding free energy of PFOA to the Trp 214 binding site is the highest among the PFOA complexes, -8.0 kcal/mol, in good agreement with literature experimental data. The PFOS binding site with the highest energy, -8.8 kcal/mol, is located near the Trp 214 binding site, thus partially affecting its activity. The maximum number of ligands that can be bound to HSA is 9 for PFOA and 11 for PFOS. The calculated data were adopted to predict the level of complexation of HSA as a function of the concentration of PFOA and PFOS found in human blood for different levels of exposition. The analysis of the factors contributing to the complex binding energy permitted to outline a set of guidelines for the rational design of alternative fluorinated surfactants with a lower bioaccumulation potential.

Experimental characterization of the mechanism of perfluorocarboxylic acids' liver protein bioaccumulation: The key role of the neutral species

Perfluorocarboxylic acids (PFCAs) of chain length greater than seven carbon atoms bioconcentrate in the livers of fish. However, a mechanistic cause for the empirically observed increase in the bioconcentration potential of PFCAs as a function of chain length has yet to be determined. To this end, recombinant rat liver fatty acid-binding protein (L-FABP) was purified, and its interaction with PFCAs was characterized in an aqueous system at pH 7.4. Relative binding affinities of L-FABP with PFCAs of carbon chain lengths of five to nine were established fluorimetrically. The energetics, mechanism, and stoichiometry of the interaction of perfluorooctanoic acid (PFOA) with L-FABP were examined further by isothermal titration calorimetry (ITC) and electrospray ionization combined with tandem mass spectrometry (ESI-MS/MS). Perfluorooctanoic acid was shown to bind to L-FABP with an affinity approximately an order of magnitude less than the natural ligand, oleic acid, and to have at least 3:1 PFOA:L-FABP stoichiometry. Two distinct modes of PFOA binding to L-FABP were observed by ESI-MS/MS analysis; in both cases, PFOA binds solely as the neutral species under typical physiological pH and aqueous concentrations of the anion. A comparison of their chemical and physical properties with other well-studied biologically relevant chemicals showed that accumulation of PFCAs in proteins as the neutral species is predictable. For example, the interaction of PFOA with L-FABP is almost identical to that of the acidic ionizing drugs ketolac, ibuprofen, and warfarin that show specificity to protein partitioning with a magnitude that is proportional to the K(OW) (octanol-water partitioning) of the neutral species. The experimental results suggest that routine pharmacochemical models may be applicable to predicting the protein-based bioaccumulation of long-chain PFCAs.