Screening of the Antagonistic Activity of Potential Bisphenol A Alternatives toward the Androgen Receptor Using Machine Learning and Molecular Dynamics Simulation.

Over the past few decades, extensive research has indicated that exposure to bisphenol A (BPA) increases the health risks in humans. Toxicological studies have demonstrated that BPA can bind to the androgen receptor (AR), resulting in endocrine-disrupting effects. In recent investigations, many alternatives to BPA have been detected in various environmental media as major pollutants. However, related experimental evaluations of BPA alternatives have not been systematically implemented for the assessment of chemical safety and the effects of structural characteristics on the antagonistic activity of the AR. To promote the green development of BPA alternatives, high-throughput toxicological screening is fundamental for prioritizing chemical tests. Therefore, we proposed a hybrid deep learning architecture that combines molecular descriptors and molecular graphs to predict AR antagonistic activity. Compared to previous models, this hybrid architecture can extract substantial chemical information from various molecular representations to improve the model's generalization ability for BPA alternatives. Our predictions suggest that lignin-derivable bisguaiacols, as alternatives to BPA, are likely to be nonantagonist for AR compared to bisphenol analogues. Additionally, molecular dynamics (MD) simulations identified the dihydrotestosterone-bound pocket, rather than the surface, as the major binding site of bisphenol analogues. The conformational changes of key helix H12 from an agonistic to an antagonistic conformation can be evaluated qualitatively by accelerated MD simulations to explain the underlying mechanism. Overall, our computational study is helpful for toxicological screening of BPA alternatives and the design of environmentally friendly BPA alternatives.

Molecular-Scale Investigation on the Formation of Brown Carbon Aerosol via Iron-Phenolic Compound Reactions in the Dark.

Brown carbon (BrC) is one of the most mysterious aerosol components responsible for global warming and air pollution. Iron (Fe)-induced catalytic oxidation of ubiquitous phenolic compounds has been considered as a potential pathway for BrC formation in the dark. However, the reaction mechanism and product composition are still poorly understood. Herein, 13 phenolic precursors were employed to react with Fe under environmentally relevant conditions. Using Fourier transform ion cyclotron resonance mass spectrometry, a total of 764 unique molecular formulas were identified, and over 85% of them can be found in atmospheric aerosols. In particular, products derived from precursors with catechol-, guaiacol-, and syringol-like-based structures can be distinguished by their optical and molecular characteristics, indicating the structure-dependent formation of BrC from phenolic precursors. Multiple pieces of evidence indicate that under acidic conditions, the contribution of either autoxidation or oxygen-induced free radical oxidation to BrC formation is extremely limited. Ligand-to-Fe charge transfer and subsequent phenoxy radical coupling reactions were the main mechanism for the formation of polymerization products with high molecular diversity, and the efficiency of BrC generation was linearly correlated with the ionization potential of phenolic precursors. The present study uncovered how chemically diverse BrC products were formed by the Fe-phenolic compound reactions at the molecular level and also provide a new paradigm for the study of the atmospheric aerosol formation mechanism.

Development of a Completely New PFOS Alternative with Lower Surface Tension for Minimizing the Environmental Burden.

Improving the technical performance of related industrial products is an efficient strategy to reducing the application quantities and environmental burden for toxic chemicals. A novel polyfluoroalkyl surfactant potassium 1,1,2,2,3,3,4,4-octafluoro-4-(perfluorobutoxy)butane-1-sulfonate(F404) was synthesized by a commercializable route. It had a surface tension(γ) of 18.2 mN/m at the critical micelle concentration(CMC, 1.04 g/L), significantly lower than that of perfluorooctane sulfonate(PFOS, ca. 33.0 mN/m, 0.72 g/L), and exhibited remarkable suppression of chromium-fog at a dose half that of PFOS. The half maximal inhibitory concentration(IC50) values in HepG2 cells and the lethal concentration of 50%(LC50) in zebrafish embryos after 72 hpf indicated a lower toxicity for F404 in comparison to PFOS. In a UV/sulphite system, 89.3% of F404 were decomposed after 3 h, representing a defluorination efficiency of 43%. The cleavage of the ether C-O bond during the decomposition would be expected to form a short chain·C4F9 as the position of the ether C-O in the F404 fluorocarbon chains is C4-O5. The ether unit is introduced in the perfluoroalkyl chain to improve water solubility, biocompatibility and degradation, thereby minimizing the environmental burden. Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s40242-023-3030-4.

Investigation of the Binding Fraction of PFAS in Human Plasma and Underlying Mechanisms Based on Machine Learning and Molecular Dynamics Simulation.

More than 7000 per- and polyfluorinated alkyl substances (PFAS) have been documented in the U.S. Environmental Protection Agency's CompTox Chemicals database. These PFAS can be used in a broad range of industrial and consumer applications but may pose potential environmental issues and health risks. However, little is known about emerging PFAS bioaccumulation to assess their chemical safety. This study focuses specifically on the large and high-quality data set of fluorochemicals from the related environmental and pharmaceutical chemicals databases, and machine learning (ML) models were developed for the classification prediction of the unbound fraction of compounds in plasma. A comprehensive evaluation of the ML models shows that the best blending model yields an accuracy of 0.901 for the test set. The predictions suggest that most PFAS (∼92%) have a high binding fraction in plasma. Introduction of alkaline amino groups is likely to reduce the binding affinities of PFAS with plasma proteins. Molecular dynamics simulations indicate a clear distinction between the high and low binding fractions of PFAS. These computational workflows can be used to predict the bioaccumulation of emerging PFAS and are also helpful for the molecular design of PFAS to prevent the release of high-bioaccumulation compounds into the environment.

Effect of Enterohepatic Circulation on the Accumulation of Per- and Polyfluoroalkyl Substances: Evidence from Experimental and Computational Studies.

The pharmacokinetic characteristics of per- and polyfluoroalkyl substances (PFAS) affect their distribution and bioaccumulation in biological systems. The enterohepatic circulation leads to reabsorption of certain chemicals from bile back into blood and the liver and thus influences their elimination, yet its influence on PFAS bioaccumulation remains unclear. We explored the role of enterohepatic circulation in PFAS bioaccumulation by examining tissue distribution of various PFAS in wild fish and a rat model. Computational models were used to determine the reabsorbed fractions of PFAS by calculating binding affinities of PFAS for key transporter proteins of enterohepatic circulation. The results indicated that higher concentrations were observed in blood, the liver, and bile compared to other tissues for some PFAS in fish. Furthermore, exposure to a PFAS mixture on the rat model showed that the reabsorption phenomenon appeared during 8-12 h for most long-chain PFAS. Molecular docking calculations suggest that PFAS can bind to key transporter proteins via electrostatic and hydrophobic interactions. Further regression analysis adds support to the hypothesis that binding affinity of the apical sodium-dependent bile acid transporter is the most important variable to predict the human half-lives of PFAS. This study demonstrated the critical role of enterohepatic circulation in reabsorption, distribution, and accumulation of PFAS.

Evaluation of the Estrogenic/Antiestrogenic Activities of Perfluoroalkyl Substances and Their Interactions with the Human Estrogen Receptor by Combining In Vitro Assays and In Silico Modeling.

The potential estrogenic activities of perfluoroalkyl substances (PFASs) are controversial. Here, we investigated the estrogenic/antiestrogenic activities of PFASs and explored the corresponding interaction mode of PFASs with the estrogen receptor (ER) by combining in vitro assays and in silico modeling. We found that three PFASs (perfluorobutanoic acid, perfluorobutane sulfonate, and perfluoropentanoic acid) exerted antiestrogenic effects by inhibiting luciferase activity, whereas perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) exerted estrogenic effects by inducing luciferase activity. When coexposed to 17ß-estradiol (E2), all tested PFASs attenuated the E2-stimulated luciferase activity; unexpectedly, each PFAS could further attenuate the luciferase activity generated by the cotreatment with ICI 182,780 and E2, with a minimal effective concentration comparable to that found in human serum. PFHxS and PFOS significantly induced the gene expression of TFF1; additionally, all PFASs inhibited the E2-induced gene expression of TFF1 and EGR3. Furthermore, the results of the blind docking analyses suggested that the interaction with the coactivator-binding region on the ER surface should be included as a pathway through which PFASs exert estrogenic and antiestrogenic activities. Finally, we revealed the critical molecular property of the zero-order molecular connectivity index (MCI) (0χ) that affects the antiestrogenic activity of PFASs.

Structure-Oriented Research on the Antiestrogenic Effect of Organophosphate Esters and the Potential Mechanism.

Organophosphate esters (OPEs) can exhibit various toxicities including endocrine disruption activity. Unfortunately, the low-dose endocrine-disrupting effects mediated by estrogen receptors (ERs) are commonly underestimated for OPEs and their metabolites. Here, structure-oriented research was performed to investigate the estrogenic/antiestrogenic effect of 13 OPEs (including three metabolites) and the potential mechanism. All of the OPEs exerted antiestrogenic activities in both E-screen and MVLN assays. OPEs with bulky substituents, such as phenyl rings (triphenyl phosphate (TPP), tricresyl phosphate (TCP), diphenylphosphoryl chloride, and diphenylphosphite) or relatively long alkyl chains (dibutylbutylphosphonate (DBBP)), exerted relatively strong ER antagonism potency at micromolar concentrations. The established quantitative structure-activity relationship indicated that the antiestrogenic activities of the OPEs mainly depended on the volume, leading eigenvalue, and hydrophobicity of the molecule. Molecular docking revealed that the three OPEs with the bulkiest substituents on the phosphate ester group (TPP, TCP, and DBBP) have a similar interaction mode to the classical ER antagonist 4-hydroxytamoxifen. The correlation between the antiestrogenic activity and the corresponding ER binding affinity was statistically significant, strongly suggesting that the OPEs possess the classical antagonism mechanism of interfering with the positioning of helix 12 in the ER.

Screening of Potential PFOS Alternatives To Decrease Liver Bioaccumulation: Experimental and Computational Approaches.

Perfluorooctanesulfonate (PFOS) is a persistent organic pollutant with significant bioaccumulation potential in liver tissues. Exposure to PFOS could cause increase of liver weight, induce adenomas of the liver, and cause hepatomegaly. Alternatives of PFOS might be designed and synthesized that have significantly lower liver bioaccumulation. In this study, we conducted animal exposure experiments to investigate tissue accumulations of 14 per- and polyfluoroalkyl substances. Correlation analysis demonstrated that accumulation of the compounds in rat liver had strong correlations with their binding affinities of liver fatty acid binding protein (LFABP). Thus, we combined a quantitative structure-activity relationship model with molecular dynamics (MD) simulations to develop computational models to predict the LFABP binding affinities of two newly synthesized alternatives, perfluorodecalin-2-sulfonic acid and N-diperfluorobutanoic acid. The binding characteristics of the PFOS alternatives for LFABP were elaborated to explore how the different structural modifications of molecules influenced the underlying binding mechanisms. Subsequent animal experiments demonstrated that the binding free energy calculations based on the MD simulations provided a good indicator to reflect the relative degree of liver accumulation of the PFOS alternatives in the same exposure doses and durations. Our findings from the combination of experimental exposure and computational model can provide helpful information to design potential alternatives of PFOS with weak LFABP binding capability and low liver accumulation.

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.

Application of a Novel Coarse-Grained Soil Organic Matter Model in the Environment.

Soil organic matter (SOM) is ubiquitous in the environment. Intensive efforts have been made to find effective ways to assess the interaction of SOM with contaminants since such interactions are one of the important criteria used to evaluate the migration, persistency and bioavailability of chemicals in the environment. This study aims to extend the application of coarse-grained (CG) dissipative particle dynamics (DPD) to the water/SOM system and predict contaminant mobility in the system. The CG model was based on the Vienna Soil-Organic-Matter Modeler, which can generate flexible condensed-phase models of SOM. A series of DPD simulations was performed to investigate the mobility of perfluorinated sulfonic acids (PFSAs) and hexachlorobutadiene (HCBD). The results indicated that the mobility of PFSAs decreased with increasing length in the carbon chain. In addition, HCBD and hexachlorobenzene (HCB) have similar diffusion coefficients, indicating analogous behavior in SOM. Moreover, water-containing SOM layers may reflect a more realistic situation. This work, coupling the CG method with DPD simulation, provides a new high-efficiency tool to assess the behavior of contaminants in the environment.

Anti-estrogenic activity of tris(2,3-dibromopropyl) isocyanurate through disruption of co-activator recruitment: experimental and computational studies.

As a potential endocrine disruptor, tris(2,3-dibromopropyl) isocyanurate (TBC) has previously been demonstrated to reduce expression of estrogen-dependent vitellogenin (vtg) mRNA in adult zebrafish. However, the underlying toxicity pathways and molecular mechanisms involved in TBC-induced endocrine disruption remain elusive. In the current study, E-Screen and MVLN assays were employed to explore the potential anti-estrogenic effects of TBC via the estrogen receptor α (ERα)-mediated signaling pathway. Within a dose range between 1 × 10- 9 and 1 × 10- 7 M, TBC significantly inhibited 17ß-estradiol (E2)-induced cell proliferation in a breast cancer cell line. The luciferase activity induced by E2 was also significantly inhibited by TBC in a dose-dependent manner. Moreover, neither TBC nor E2 affected proliferation of the ERα-negative breast cancer cell line MDA-MB-231. These experimental results confirmed that TBC has anti-estrogenic effects by affecting the ERα-mediated signaling pathway. By comparing TBC with known antagonists of ERα, we found that TBC has similar molecular structure as certain co-activator binding inhibitors. Therefore, using molecular docking and molecular dynamics simulations, TBC was further predicted to competitively occupy the surface site of ERα rather than the canonical E2-binding pocket of ERα, thus disrupt subsequent co-activator recruitment and transcription activation. Our findings elucidate the anti-estrogenic mechanism of TBC at the atomic level and highlight the biological importance of surface sites of nuclear receptors for a risk assessment of potential environmental pollutants.

Experimental and computational insights on the recognition mechanism between the estrogen receptor α with bisphenol compounds.

Certain bisphenols (BPs) have been regarded as endocrine-disrupting chemicals due to their structural similarities to bisphenol A (BPA), a well-known weak estrogenic chemical. However, very limited data are currently available on the relationship between estrogenic activity and the structure of BP analogs. Therefore, we systematically investigated the estrogenic potency of 14 selected BP analogs with typical structures using experimental and computational methods. Most of the tested BP analogs exhibited weak estrogenic activities in both cell proliferation and MVLN assays with the exception of TBBPA, TCBPA and TBBPS. Molecular modeling techniques have been performed to investigate the dynamic structural characteristics of recognition processes between BPs and estrogen receptor α (ERα) at the atomic level. Thr347 was identified as the key residue responsible for the recognition of TBBPA, TCBPA and TBBPS by means of induced-fit H-bonding interactions in the binding pocket of ERα, whereas other BPs, in turn, rely on the alternative formation of H-bonds with His524. Subsequent allosteric modulation interferes significantly with the stability of helix 12 that is crucial for the transcriptional activity of ERα. These structural perturbations that are induced by the three compounds were further confirmed to reduce the recruitment potency of co-activators more than other BPs based on calculations of binding free energies, which is in line with observed experimental transcriptional activities. Our findings may help to elucidate the estrogenic potency of BPs with different molecular structures.

Differential accumulation and elimination behavior of perfluoroalkyl Acid isomers in occupational workers in a manufactory in China.

In this study, serum and urine samples were collected from 36 occupational workers in a fluorochemical manufacturing plant in China from 2008 to 2012 to evaluate the body burden and possible elimination of linear and branched perfluoroalkyl acids (PFAAs). Indoor dust, total suspended particles (TSP), diet, and drinking water samples were also collected to trace the occupational exposure pathway to PFAA isomers. The geometric mean concentrations of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS) isomers in the serum were 1386, 371, and 863 ng mL(-1), respectively. The linear isomer of PFOS, PFOA, and PFHxS was the most predominant PFAA in the serum, with mean proportions of 63.3, 91.1, and 92.7% respectively, which were higher than the proportions in urine. The most important exposure routes to PFAA isomers in the occupational workers were considered to be the intake of indoor dust and TSP. A renal clearance estimation indicated that branched PFAA isomers had a higher renal clearance rate than did the corresponding linear isomers. Molecular docking modeling implied that linear PFOS (n-PFOS) had a stronger interaction with human serum albumin (HSA) than branched isomers did, which could decrease the proportion of n-PFOS in the blood of humans via the transport of HSA.

NeuTox: A weighted ensemble model for screening potential neuronal cytotoxicity of chemicals based on various types of molecular representations.

Chemical-induced neurotoxicity has been widely brought into focus in the risk assessment of chemical safety. However, the traditional in vivo animal models to evaluate neurotoxicity are time-consuming and expensive, which cannot completely represent the pathophysiology of neurotoxicity in humans. Cytotoxicity to human neuroblastoma cell line (SH-SY5Y) is commonly used as an alternative to animal testing for the assessment of neurotoxicity, yet it is still not appropriate for high throughput screening of potential neuronal cytotoxicity of chemicals. In this study, we constructed an ensemble prediction model, termed NeuTox, by combining multiple machine learning algorithms with molecular representations based on the weighted score of Particle Swarm Optimization. For the test set, NeuTox shows excellent performance with an accuracy of 0.9064, which are superior to the top-performing individual models. The subsequent experimental verifications reveal that 5,5'-isopropylidenedi-2-biphenylol and 4,4'-cyclo-hexylidenebisphenol exhibited stronger SH-SY5Y-based cytotoxicity compared to bisphenol A, suggesting that NeuTox has good generalization ability in the first-tier assessment of neuronal cytotoxicity of BPA analogs. For ease of use, NeuTox is presented as an online web server that can be freely accessed via http://www.iehneutox-predictor.cn/NeuToxPredict/Predict.

Occurrence, placental transfer, and health risks of emerging endocrine-disrupting chemicals in pregnant women.

Previous studies demonstrated that many environmental chemicals can cross the human placental barrier. However, the risk regarding gestational exposure of emerging endocrine-disrupting chemicals (EDCs) is unclear. In this study, the occurrence of 24 EDCs, such as bisphenol A analogs, parabens, triclocarban, and triclosan, was investigated in serum and urine samples from Chinese pregnant women. Some metabolites were determined in matched serum-urine pairs (n = 75) to perform a comprehensive assessment of exposure. The placental transfer efficiency (PTE) of the detected chemicals was determined in matched maternal-cord serum pairs (n = 110). The mean PTEs of the chemicals showed a large variation from 43.1% to 171.0%. The potential effects of physicochemical properties, molecular structures, and biological factors on PTE were investigated using multiple linear regression models and molecular docking. We found that the PTE of methyl paraben, ethyl paraben, and propyl paraben was associated with their increasing alkyl chain lengths. Furthermore, a comprehensive exposure assessment of EDCs showed that 62.7% of pregnant women had a health index > 1, which indicted potential health risks during pregnancy. However, toxicity and the underlying mechanisms of these EDCs remain to be further studied.

Antagonistic mechanisms of bisphenol analogues on the estrogen receptor α in zebrafish embryos: Experimental and computational studies.

Bisphenol A (BPA) can disturb the estrogen receptor α (ERα)-mediated signaling pathway, which results in endocrine-disrupting effects and reproductive toxicity. Most BPA analogues as alternatives were evidenced to generate estrogenic activity as agonists or partial agonists of ERα. Recent studies indicated that certain BPA analogues, such as bisphenol M (BPM), bisphenol P (BPP), and bisphenol FL (BPFL), exhibited strong anti-estrogenic effects comparable with the typical antagonist 4-hydroxytamoxifen. However, conflicting findings were also observed for the compounds in different in vitro assays, and whether these BPA analogues can elicit an in vivo effect on ERα at environmentally relevant concentrations remains unknown. The underlying structural basis of estrogenic/anti-estrogenic activity should be further elucidated at the atomic level. To address these issues, we combined zebrafish-based in vivo and in silico methods to assess the effects of the compounds on ERα. The results show that the expressions of ERα-mediated downstream related genes in zebrafish embryos decreased after exposed to the compounds. Further molecular dynamics simulations were used to probe the antagonistic mechanisms of the compounds on ERα. The key H-bonding interactions were identified as important ligand recognition by ERα in the analysis of binding modes and binding free energy calculations. In summary, the current study provides preliminary in vivo evidence of fish species for the anti-estrogenic activity of certain BPA analogues.

Mitochondrial ATP synthase as a direct molecular target of chromium(III) to ameliorate hyperglycaemia stress.

Chromium(III) is extensively used as a supplement for muscle development and the treatment of diabetes mellitus. However, its mode of action, essentiality, and physiological/pharmacological effects have been a subject of scientific debate for over half a century owing to the failure in identifying the molecular targets of Cr(III). Herein, by integrating fluorescence imaging with a proteomic approach, we visualized the Cr(III) proteome being mainly localized in the mitochondria, and subsequently identified and validated eight Cr(III)-binding proteins, which are predominately associated with ATP synthesis. We show that Cr(III) binds to ATP synthase at its beta subunit via the catalytic residues of Thr213/Glu242 and the nucleotide in the active site. Such a binding suppresses ATP synthase activity, leading to the activation of AMPK, improving glucose metabolism, and rescuing mitochondria from hyperglycaemia-induced fragmentation. The mode of action of Cr(III) in cells also holds true in type II diabetic male mice. Through this study, we resolve the long-standing question of how Cr(III) ameliorates hyperglycaemia stress at the molecular level, opening a new horizon for further exploration of the pharmacological effects of Cr(III).

Synthesis and biological evaluation of a series of podophyllotoxins derivatives as a class of potent antitubulin agents.

A series of eight novel podophyllotoxin derivatives were designed, synthesized and evaluated for biological activities. The antiproliferative activities were tested against a panel of human cancer cell lines (K562, SGC, Hela and HepG) and the inhibition of tubulin polymerization was also evaluated. Compound 8e displayed significant antiproliferative activities for all four cell lines and strong levels of tubulin polymerization inhibition effect. Combined with cell apoptosis and cell cycle analysis, it demonstrated that compound 3e that effectively interfere with tubulin dynamics prevent mitosis in cancer cells, leading to cell cycle arrest and, eventually dose dependent apoptosis. All experimental measurements were also supported by molecular docking simulations of colchicine binding site, which revealed the governing forces for the binding behavior and a good relationship with anti-tubulin activity and antiproliferative activities. The synthesis and biological studies provided an interesting new class of antitubulin agents for development of lead compounds and also a direction for further structure modification to obtain more potent anti-cancer drugs.

Insight into the defluorination ability of per- and polyfluoroalkyl substances based on machine learning and quantum chemical computations.

UV-generated hydrated electrons play a critical role in the defluorination reaction of poly- and perfluoroalkyl substances (PFAS). However, limited experimental data hinder insight into the effects of the structural characteristics of emerging PFAS on their defluorination abilities. Therefore, in this study, we adopted quantity structure-activity relationship models based on machine learning algorithms to develop the predictive models of the relative defluorination ability of PFAS. Five-fold cross-validations were used to perform the hyperparameter tuning of the models, which suggested that the gradient boosting algorithms with PaDEL descriptors as the best model possessed superior predictive performance (R2test = 0.944 and RMSEtest = 0.114). The importance of the descriptor indicated that the electrostatic properties and topological structure of the compounds significantly affected the defluorination ability of the PFAS. For the emerging PFAS the best model showed that most compounds, such as potential alternatives of perfluorooctane sulfonic acid, were recalcitrant to reductive defluorination, whereas perfluoroalkyl ether carboxylic acids had relatively stronger defluorination abilities than perfluorooctanoic acid. The theoretical calculations implied that additional electrons on PFAS could cause molecular deconstruction, such as changes in the dihedral angle involved in the carbon chain, as well as C-F bond and ether C-O bond cleavages. In general, the current computational models could be useful for screening emerging PFAS to assess their defluorination ability for the molecular design of fluorochemical structures.

Porous organic framework as coating for stir bar sorptive extraction of carbamate pesticides from corn and potato samples.

Three porous organic frameworks (POFs) were synthesized by the reaction between phloroglucinol and 1,4-phthalaldehyde, 4,4'-biphenyldialdehyde or tris-(4-formylphenyl) amine; the products are named as POF-a, POF-b and POF-c, respectively. They were used to prepare POFs coated stir bars respectively for the extraction of four carbamate pesticides (CMPs). POF-c coated stir bar exhibited better adsorption performance than POF-a/b coated stir bar and commercial stir bars, probably due to the stronger conjugated structure and hydrophobicity of POF-c, and resultant hydrophobic, π-π and hydrogen bonding interactions between them. The adsorption mechanism for target CMPs was verified by characterization techniques and molecular dynamics simulation. A method of POF-c coated stir bar sorptive extraction-high performance liquid chromatography-variable wavelength ultraviolet detector was developed for the analysis of four CMPs in corn and potato samples. Under the optimal conditions, LODs of the method were between 0.017 and 0.048 µg/L, and the linear range for four CMPs was 0.1/0.2-200 µg/L.