Search Results (40)

Per- and polyfluoroalkyl substances (PFASs) are a large class of thousands of synthetic organofluorine chemical compounds used for many industrial applications. Humans are exposed to PFASs mainly through diet and contaminated drinking water. Studies show that PFASs induce several adverse effects on humans. A great number of human biomonitoring studies have been widely conducted with the aim of estimating exposure to PFASs. The matrices mainly investigated are blood, serum and breast milk. However, in many cases, the need for non-invasive sampling methods with a minimal impact on donors has become paramount to comply with modern ethical standards and regulations. For this reason, we developed a streamlined and efficient method for the analysis of eight perfluorocarboxylic and perfluorosulfonic acids (PFHpA; PFHxS; PFOA; PFHpS; PFNA; PFOS; PFDA; and PFUdA) in human urine samples by UPLC chromatography tandem mass spectrometry. Chromatographic and MS parameters were optimized; the method was validated for: repeatability (<20%), within-lab reproducibility (<20%), trueness (within the set 20% variation limit of agreement between the mean of the data set and the true value), efficiency (51–97%), linearity (R² > 0.99), limits of detection (0.0003 ng/mL), and limits of quantification (0.001 ng/mL). To our knowledge, this is the first published method in Italy for the detection of PFASs in human urine. Full article

Preeclampsia (PE) affects 2–8% of pregnancies, yet it lacks curative treatment options. Oxidative stress caused by the release of reactive oxygen and nitrogen species (ROS/RNS) in the placenta is common in abnormal placental development. It can cause downstream signaling and the formation of anti-angiogenic factors, e.g., soluble fms-like tyrosine kinase 1 (sFLT-1), leading to symptoms of PE, such as hypertension, proteinuria, and, in severe cases, eclampsia. Mitochondria-targeted antioxidants were developed to reduce oxidative stress and alleviate PE symptoms. Ten organofluorine diaryl hydrazones were designed as potential antioxidants, synthesized, and tested for their activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and oxygen radical absorbance capacity (ORAC) assays. Compounds 2, 3, 5, and 6 showed excellent antioxidant capacity in all three assays and were tested in an in vitro human trophoblast cell culture system mimicking PE in which the cells were exposed to oxidative stress inducing the release of sFLT-1. The anti-angiogenic factor sFLT-1 was greatly reduced in cells treated with antioxidants. Compounds 5 and 6 were more effective in preventing sFLT-1 release than 2 and 3. Density functional theory calculations of the electronic structures of compounds 2, 5, and 6 were conducted at the M06-2X/6-311G+(d,p) level to further understand the reactivity profile of these molecules. The electron density of delocalized bonds (EDDB(r)) was calculated to analyze the effect of delocalization on radical stabilization. Full article

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organofluorines linked to cancer, organ dysfunction, and other health problems. This study used quantitative structure–property relationship (QSPR) and quantitative structure–activity relationship (QSAR) modeling to examine the binding of PFAS to estrogen receptor alpha (ERα) and beta (ERβ). Molecular docking of 14,591 PFAS compounds was performed, and docking scores were used as a measure of receptor affinity. QSPR models were built for two datasets: the ERα and ERβ top binders (TBs), and a set of commonly exposed (CE) PFAS. These models quantified how chemical descriptors influence binding affinity. Across the models, higher density and electrophilicity indicated positive correlations with affinity, while surface tension indicated negative correlations. Electrostatic descriptors, including HOMO energy and positive Fukui index (F⁺ max), were part of the models but showed inconsistent trends. The CE QSPR models displayed correlations that conflicted with those of the TB models. Following QSPR analysis, 66 QSAR models were developed using a mix of top binders and experimental data. These models achieved strong performance, with R² values averaging 0.95 for training sets and 0.78 for test sets, that indicated reliable predictive ability. To improve generalizability, large-set QSAR models were created for each receptor. After outlier removal, these models reached R² values of 0.68–0.71, which supports their use in screening structurally diverse PFAS. Overall, QSPR and QSAR analyses reveal key chemical features that influence PFAS–ER binding. This predictive approach provides a scalable framework to assess the binding interactions of structurally diverse PFAS to ERs and other nuclear receptors. All the codes, data, and the GUI visualization of the results are freely available at sivaGU/QSPR-QSAR-Molecular-Visualization-Tool. Full article

Per- and polyfluoroalkyl substances (PFASs), known as “forever chemicals,” are synthetic organofluorine compounds widely used since the 1940s due to their chemical and thermal stability. However, growing concerns about their environmental and human health risks have emerged. Although the toxicity of PFASs to humans has been extensively researched, their effects on microbial consortia in wastewater treatment plants (WWTPs) have not been as thoroughly investigated. This study evaluates whether aqueous wastes (AWs) containing PFASs inhibit aerobic biomasses from various WWTPs. Approximately 400 respirometric tests showed no acute toxicity. However, biomass tolerance varied based on acclimatization. Biomass from a municipal WWTP was more tolerant to AWs with short-chain PFASs, whereas biomass from a WWTP authorized to receive AWs was less inhibited by AWs rich in long-chain PFASs. These findings highlight the potential role of municipal WWTPs in treating PFAS-contaminated AWs and emphasize the need for tailored treatment strategies to minimize environmental risks. Full article

Preeclampsia (PE) is a hypertensive disorder impacting 5–7% of pregnancies globally. With no causative treatment available, diagnosed patients have limited therapeutic options, putting them at risk for pregnancy complications. The induction of oxidative stress by ROS—one of the major contributors in PE pathogenesis—causes downstream signaling and production of anti-angiogenic factors, such as sFLT1 and sEng. The anti-angiogenic factors may cause endothelial and trophoblast dysfunction, contributing to the development of hypertension, proteinuria, and in severe cases, eclampsia. To target placental oxidative stress, we developed and evaluated an organofluorine hydrazone antioxidant, HY-12, in vitro. Human trophoblast (HTR8/SVneo) cells were incubated with hydrogen peroxide to induce oxidative stress and act as a model of PE. The goal of the study was to assess the efficacy of HY-12 and its ability to reduce cell injury, mitochondrial stress, and anti-angiogenic response. In our human trophoblast-based assays, pre-treatment with HY-12 reduced mitochondrial-derived ROS production in cells exposed to hydrogen peroxide, proving its ability to alleviate the oxidative stress associated with the pathogenesis of PE. HY-12 reduced HIF1A expression and sFLT1 protein expression in H₂O₂-exposed HTR8 cells. Furthermore, HY-12 improved the activity of the mitochondrial electron chain enzyme cytochrome C oxidase (COX) in the hydrogen-peroxide-treated HTR8/SVneo cells, which is a promising attribute of the compound. In reducing placental trophoblast oxidative stress, HY-12 shows promise as a potential treatment of preeclampsia. In vivo studies are warranted to further determine the efficacy of this compound. Full article

Fluorinated organic compounds have demonstrated remarkable utility in medicinal chemistry due to their enhanced metabolic stability and potent therapeutic efficacy. Several examples exist of fluorinated non-steroidal anti-inflammatory drugs (NSAIDs), including diflunisal, flurbiprofen, and trifluoromethylated pyrazoles celecoxib and mavacoxib. These trifluoromethylated pyrazoles, which are most commonly constructed through the cyclocondensation of a trifluorinated 1,3-dicarbonyl and an aryl hydrazine, are also found in numerous other drug candidates. Here, we interrogate the effects of solvents and the presence of Brønsted or Lewis acid catalysts on catalyzing this process. We highlight the utility of benchtop ¹⁹F NMR spectroscopy in enabling the real-time quantification of reaction progress and the identification of fluorinated species present in crude reaction mixtures without the need for cost-prohibitive deuterated solvents. Ultimately, we find that the reaction solvent has the greatest impact on the rate and product yield, and also found that the relationship between the keto-enol equilibrium of the dicarbonyl starting material pyrazole formation rate is highly solvent-dependent. More broadly, we describe the optimization of the yield and kinetics of trifluoromethylpyrazole formation in the synthesis of celecoxib and mavacoxib, which is made possible through high-throughput reaction screening on benchtop NMR. Full article

Per-and Polyfluoroalkyl substances (PFASs) are recalcitrant organofluorine contaminants, which demand urgent attention due to their bioaccumulation potential and associated health risks. While numerous current treatments technologies, including certain plasma-based treatments, can degrade PFASs, their complete destruction or mineralization is seldom achieved. Extensive aqueous PFAS mineralization capability coupled with industrial-level scaling potential makes gliding arc plasma (GAP) discharges an interesting and promising technology in PFAS mitigation. In this study, the effects of GAP discharge’s thermal and reactive properties on aqueous perfluorooctanesulfonic acid (PFOS) mineralization were investigated. Treatments were conducted with air and nitrogen GAP discharges at different plasma gas temperatures to investigate the effects of plasma thermal environment on PFOS mineralization; the results show that treatments with increased plasma gas temperatures lead to increased PFOS mineralization, and discharges in air were able to mineralize PFOS at relatively lower plasma gas temperatures compared to discharges in nitrogen. Studies were conducted to identify if GAP-based PFOS mineralization is a pure thermal process or if plasma reactive chemistry also affects PFOS mineralization. This was done by comparing the effects of thermal environments with and without plasma species (air discharge and air heated to plasma gas temperatures) on PFOS mineralization; the results show that while GAP discharge was able to mineralize PFOS, equivalent temperature air without plasma did not lead to PFOS mineralization. Finally, mineralization during treatments with GAP discharges in argon and air at similar gas temperatures were compared to investigate the role of plasma species in PFOS mineralization. The results demonstrate that treatments with argon (monoatomic gas with higher ionization) lead to increased PFOS mineralization compared to treatments with air (molecular gas with lower ionization), showing the participation of reactive species in PFOS mineralization. Full article

This study introduces a novel trifluoromethylating reagent, [(bpy)Cu(O₂CCF₂SO₂F)₂], notable for not only its practical synthesis from cost-effective starting materials and scalability but also its nonhygroscopic nature. The reagent demonstrates high efficiency in facilitating trifluoromethylation reactions with various halogenated hydrocarbons, yielding products in good yields and exhibiting broad functional group compatibility. The development of [(bpy)Cu(O₂CCF₂SO₂F)₂] represents an advancement in the field of organic synthesis, potentially serving as a valuable addition to the arsenal of existing trifluoromethylating agents. Full article

Fenofibrate is known as a lipid-lowering drug. Although previous studies have reported that fenofibrate exhibits potential antitumor activities, IC₅₀ values of fenofibrate could be as high as 200 μM. Therefore, we investigated the antitumor activities of six synthesized fenofibrate derivatives. We discovered that one compound, SIOC-XJC-SF02, showed significant antiproliferative activity on human hepatocellular carcinoma (HCC) HCCLM3 cells and HepG2 cells (the IC₅₀ values were 4.011 μM and 10.908 μM, respectively). We also found this compound could inhibit the migration of human HCC cells. Transmission electron microscope and flow cytometry assays demonstrated that this compound could induce apoptosis of human HCC cells. The potential binding sites of this compound acting on human HCC cells were identified by mass spectrometry-cellular thermal shift assay (MS-CETSA). Molecular docking, Western blot, and enzyme activity assay-validated binding sites in human HCC cells. The results showed that fumarate hydratase may be a potential binding site of this compound, exerting antitumor effects. A xenograft model in nude mice demonstrated the anti-liver cancer activity and the mechanism of action of this compound. These findings indicated that the antitumor effect of this compound may act via activating fumarate hydratase, and this compound may be a promising antitumor candidate for further investigation. Full article

Herpes Simplex Virus (HSV) 1 and 2 are persistent infections that affect a significant percentage of United States (US) adults, with 48% having HSV-1 and 12% having HSV-2. Using data stratified by HSV-1 and HSV-2 exposures, this study investigated the association of per- and polyfluoroalkyl substances (PFAS), a group of toxic synthetic organofluorine chemical compounds found in environmental, occupational, and home settings, with allostatic load (AL), an index of chronic physiological stress. Descriptive statistics, multivariable logistic regression, and Bayesian Kernel Machine Regression (BKMR) modeling were used to assess the effects of multi-PFAS exposures on AL using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2014. Results indicated participants not exposed to PFAS exhibited 77% to 97% lower odds of higher AL (p < 0.001). For example, PFOS per unit increase brought forth a 2% odds increase in higher AL (OR: 1.02; 95% CI: 1.00, 1.05; p < 0.05). Participants exposed to PFAS had reduced odds of higher AL (77%–79%), regardless of their HSV-1 and HSV-2 status. PFAS exposure was more prevalent in those with HSV-1 (60%) than in those with HSV-2 (20%) infection, while AL levels were comparable in both groups (17%). BKMR revealed a nonlinear PFAS-AL association and confirmed interactions among PFAS. In summary, PFAS exposure increased the likelihood of higher AL among those with persistent HSV infections. Our study enhances the current understanding of the complex dynamics involving PFAS, persistent infections, and AL, which hold significant implications for public health and clinical intervention strategies. Full article

Per- and polyfluoroalkyl substances (PFAS) constitute a group of organofluorine chemical synthetic compounds widely used in industries and manufacturing due to their hydrophobic properties. However, PFAS have been found to cause negative human health outcomes. Therefore, a strong interest in the possible removal of these compounds from wastewater (WW) has been shown. This work aims to present a systematic analysis of the scientific literature related to the innovative and alternative adsorbent materials that can be used for treating PFAS-contaminated WW. Moreover, the adsorption processes are considered, focusing the attention on virgin adsorbent materials and biochar as adsorbents. Virgin adsorbent materials comprise conventional adsorbent materials, functional clays, metal–organic frameworks, and functionalized organic polymers. Biochar includes materials obtained from agricultural or food residues and from sewage sludge. The review shows that conventional treatment units using virgin adsorbent materials are characterized by high adsorption capacity, but also high costs. In addition, the refunctionalization of adsorbent materials is difficult to obtain. On the contrary, biochar, which is a residual product of other production processes, appears to be a cost-effective solution. Full article