Fluorine contamination, mobility, and risks in soils at a phosphate-gypsum waste landfill: a new analytical method and comparison with previous methods.

This study used a new X-ray fluorescence (XRF)-based analytical method with better precision and sensitivity to evaluate the fluorine concentrations in soil. It was hypothesized that the XRF method with a pellet-synthesizing procedure may effectively analyze the fluorine concentrations in soil with ease and reliability. The total fluorine concentrations determined using XRF were compared with those determined using three different types of analytical protocols-incineration/distillation, alkaline fusion, and aqua regia extraction procedures. Among the three procedures, the incineration/distillation procedure did not show reliable precision and reproducibility. In contrast, the total fluorine concentrations determined using the XRF analysis were linearly correlated with those determined using the alkaline fusion and aqua regia extraction procedures. Based on the results of the Korean waste leaching procedure and toxicity characteristics leaching procedure, the leachability of fluorine from soil and waste was not directly related to total fluorine concentrations in soil. Risk assessment also revealed that the fluorine-rich soils did not show non-carcinogenic toxic effects, despite exceeding the regulation level (800 mg/kg) in South Korea for total fluorine concentrations in soil. Our results suggest that XRF analysis in combination with the newly developed pretreatment method may be a promising alternative procedure for easily and rapidly determining the total fluorine concentration in soil. However, further efforts are needed to evaluate fluorine leachability and its associated risks in fluorine-contaminated soils.

[18F]-Radiolabelled Nanoplatforms: A Critical Review of Their Intrinsic Characteristics, Radiolabelling Methods, and Purification Techniques.

A wide range of nano-objects is found in many applications of our everyday life. Recognition of their peculiar properties and ease of functionalization has prompted their engineering into multifunctional platforms that are supposed to afford efficient tools for the development of biomedical applications. However, bridging the gap between bench to bedside cannot be expected without a good knowledge of their behaviour in vivo, which can be obtained through non-invasive imaging techniques, such as positron emission tomography (PET). Their radiolabelling with [18F]-fluorine, a technique already well established and widely used routinely for PET imaging, with [18F]-FDG for example, and in preclinical investigation using [18F]-radiolabelled biological macromolecules, has, therefore, been developed. In this context, this review highlights the various nano-objects studied so far, the reasons behind their radiolabelling, and main in vitro and/or in vivo results obtained thereof. Then, the methods developed to introduce the radioelement are presented. Detailed indications on the chemical steps involved are provided, and the stability of the radiolabelling is discussed. Emphasis is then made on the techniques used to purify and analyse the radiolabelled nano-objects, a point that is rarely discussed despite its technical relevance and importance for accurate imaging. The pros and cons of the different methods developed are finally discussed from which future work can develop.

Comparison of the shear bond strengths of two different polyetheretherketone (PEEK) framework materials and CAD-CAM veneer materials.

BACKGROUND: This study evaluated the shear bond strength (SBS) of two different polyetheretherketone (PEEK) and CAD-CAM materials after aging. METHODS: A total of 42 frameworks were designed and milled from 2 different PEEK discs (Copra Peek, P and BioHPP, B). P and B frameworks were divided into 3 subgroups (n = 7). 14 slices were prepared each from feldspathic ceramic (Vitablocs Mark II, VM), hybrid nanoceramic (Cerasmart, CS), and polymer-infiltrated ceramic (Vita Enamic, VE) blocks. After surface preparations, the slices were cemented to P and B surfaces. The samples were subjected to thermal aging (5000 cycles). SBS of all the samples was measured. Fractured surfaces were examined by SEM/EDX analysis. The Shapiro-Wilk, Two-way Robust ANOVA and Bonferroni correction tests were used to analyze the data (a = .05). RESULTS: Frameworks, ceramics, and frameworks x ceramics had significant differences (p < 0.05). The highest SBS value was seen in B-VM (p < 0.05). VM offered the highest SBS with both P and B. The differences between P-VM, P-CS, P-VE and B-CS and B-VE were insignificant (p > 0.05). According to EDX analysis, ytterbium and fluorine was seen in B content, unlike P. While VM and CS contained fluorine, barium, and aluminum; sodium and aluminum were observed in the VE structure. CONCLUSION: Bonding of P and B with VM offers higher SBS. VM, CS and VE did not make any difference in SBS for P, however VM showed a significant difference for B.

Radical fluorine transfer catalysed by an engineered nonheme iron enzyme.

Nonheme iron enzymes stand out as one of the most versatile biocatalysts for molecular functionalization. They facilitate a wide array of chemical transformations within biological processes, including hydroxylation, chlorination, epimerization, desaturation, cyclization, and more. Beyond their native biological functions, these enzymes possess substantial potential as powerful biocatalytic platforms for achieving abiological metal-catalyzed reactions, owing to their functional and structural diversity and high evolvability. To this end, our group has recently engineered a series of nonheme iron enzymes to employ non-natural radical-relay mechanisms for abiological radical transformations not previously known in biology. Notably, we have demonstrated that a nonheme iron enzyme, (S)-2-hydroxypropylphosphonate epoxidase from Streptomyces viridochromogenes (SvHppE), can be repurposed into an efficient and selective biocatalyst for radical fluorine transfer reactions. This marks the first known instance of a redox enzymatic process for C(sp3)F bond formation. This chapter outlines the detailed experimental protocol for engineering SvHPPE for fluorination reactions. Furthermore, the provided protocol could serve as a general guideline that might facilitate other engineering endeavors targeting nonheme iron enzymes for novel catalytic functions.

Synthesis of fluorinated amino acids by low-specificity, promiscuous aldolases coupled to in situ fluorodonor generation.

Fluorine (F) is an important element in the synthesis of molecules broadly used in medicine, agriculture, and materials. F addition to organic structures represents a unique strategy for tuning molecular properties, yet this atom is rarely found in Nature and approaches to produce fluorometabolites (such as fluorinated amino acids, key building blocks for synthesis) are relatively scarce. This chapter discusses the use of L-threonine aldolase enzymes (LTAs), a class of enzymes that catalyze reversible aldol addition to the α-carbon of glycine. The C-C bond formation ability of LTAs, together with their known substrate promiscuity, make them ideal for in vitro F biocatalysis. Here, we describe protocols to harness the activity of the low-specificity LTAs isolated from Escherichia coli and Pseudomonas putida on 2-fluoroacetaldehyde to efficiently synthesize 4-fluoro-L-threonine in vitro. This chapter also provides a comprehensive account of experimental protocols to implement these activities in vivo. These methods are illustrative and can be adapted to produce other fluorometabolites of interest.

Defluorination as the key trait to gauge the biodegradability of fluorinated pollutants in environmental microbial communities.

Research on microbial defluorination is largely centred on controlled experiments using axenic or well defined microbial inocula. These approaches serve a relevant purpose in the field, offering fundamental biochemical and mechanistic insights on the intricacies of biological defluorination. However, they fail to account for the effective contribution of environmental microbial communities in the recycling of fluoroorganic pollutants, a highly relevant perspective from an environmental risk assessment standpoint, while also missing an important outlook on how community-wide dynamics can leverage the breakdown of C─F bonds in these recalcitrant compounds. With that in mind, this chapter provides experimental and methodological insights on the study of microbial defluorination in wild environmental communities, using this critical catabolic step as the de facto endpoint to evolve, select and cultivate microorganisms with improved defluorination performances.

[Investigation and analysis of acute poisoning of organic fluorine mixed gas in a fluorine polymerization plant].

In January 2021, an acute chemical poisoning incident occurred at a fluorine polymerization plant. Through the analysis of the occupational health situation of the enterprise, combined with the clinical manifestations of the poisoned patients and the laboratory examination results, it was determined that the incident was an acute poisoning incident caused by the inhalation of organic fluorine mixed gas in the fluorine polymerization plant. Subsequently, it was clarified that the accident was caused by the illegal operation of the employees of the fluorine polymerization plant, which caused the discharge of the organic fluorine mixed gas containing high concentration of octafluoroisobutene, resulting in the poisoning of the on-site construction personnel. In order to avoid the occurrence of similar incidents, enterprises should implement the main responsibility of safety production, regularly organize supervision and inspection, eliminate illegal operations, conduct safety education and training for the staff of the unit and outsourced staff, and improve the emergency rescue ability of sudden poisoning incidents.

Asymmetric α-Fluoroalkyl-α-Amino Acids: Recent Advances in Their Synthesis and Applications.

Due to the specific properties provided by fluorine atoms to biomolecules, amino acids with fluorinated side chains are of great interest for medicinal chemistry and chemical biology. Among them, α-fluoroalkyl-α-amino acids constitute a unique class of compounds. In this review, we outline the strategies adopted for their syntheses in enantiopure or enantioenriched forms and their incorporation into peptides. We then describe the consequences of the introduction of fluorine atoms in these compounds for the modulation of their hydrophobicity and the control of their conformation. Emerging applications are presented in the areas of enzyme inhibition, medicinal chemistry, hydrolytic stability of peptides, antimicrobial peptides, PET, and 19F NMR probes.

Extending the Range of Distances Accessible by 19F Electron-Nuclear Double Resonance in Proteins Using High-Spin Gd(III) Labels.

Fluorine electron-nuclear double resonance (19F ENDOR) has recently emerged as a valuable tool in structural biology for distance determination between F atoms and a paramagnetic center, either intrinsic or conjugated to a biomolecule via spin labeling. Such measurements allow access to distances too short to be measured by double electron-electron resonance (DEER). To further extend the accessible distance range, we exploit the high-spin properties of Gd(III) and focus on transitions other than the central transition (|-1/2⟩ ↔ |+1/2⟩), that become more populated at high magnetic fields and low temperatures. This increases the spectral resolution up to ca. 7 times, thus raising the long-distance limit of 19F ENDOR almost 2-fold. We first demonstrate this on a model fluorine-containing Gd(III) complex with a well-resolved 19F spectrum in conventional central transition measurements and show quantitative agreement between the experimental spectra and theoretical predictions. We then validate our approach on two proteins labeled with 19F and Gd(III), in which the Gd-F distance is too long to produce a well-resolved 19F ENDOR doublet when measured at the central transition. By focusing on the |-5/2⟩ ↔ |-3/2⟩ and |-7/2⟩ ↔ |-5/2⟩ EPR transitions, a resolution enhancement of 4.5- and 7-fold was obtained, respectively. We also present data analysis strategies to handle contributions of different electron spin manifolds to the ENDOR spectrum. Our new extended 19F ENDOR approach may be applicable to Gd-F distances as large as 20 Å, widening the current ENDOR distance window.

Design, Synthesis, and Activity Evaluation of Fluorine-Containing Scopolamine Analogues as Potential Antidepressants.

This study aimed to develop novel rapid-acting antidepressants with sustained efficacy and favorable safety profiles. We designed and synthesized a series of fluorine-containing scopolamine analogues and evaluated their antidepressant potential. In vitro cytotoxicity assays showed that most of these compounds exhibited minimal toxicity against neuronal and non-neuronal mammalian cell lines (IC50 > 100 µM). The antidepressant activities of the compounds were evaluated using the tail suspension test, and S-3a was identified as a lead compound with potent and sustained antidepressant effects. Behaviorally, S-3a alleviated depressive symptoms in mice and displayed a higher cognitive safety margin than scopolamine. Toxicological assessments confirmed S-3a's safety, while pharmacokinetics showed a rapid clearance (half-life: 16.6 min). Mechanistically, S-3a antagonized M1 receptors and elevated BDNF levels, suggesting its potential as an antidepressant for further exploration.

Fluorine materials scavenge excess carbon dioxide and promote Escherichia coli growth.

Fluorinated solvents have been used as oxygen carriers in closed microbial cultures to sustain aerobic conditions. However, the growth-promoting effects of fluorinated solvents remain unclear. Therefore, this study aimed to elucidate the mechanism by which fluorinated solvents promote microbial growth and to explore alternative materials that can be easily isolated after culture. Escherichia coli and HFE-7200, a fluorinated solvent, were used to explore factors other than oxygen released by fluorinated solvents that promote microbial growth. E. coli growth was promoted in gas-permeable cultures, and HFE-7200 alleviated medium acidification. Gas chromatography confirmed that HFE-7200 functioned as a scavenger of carbon dioxide produced by E. coli metabolism. Because fluorinated solvents can dissolve various gases, they could scavenge metabolically produced toxic gases from microbial cultures. Furthermore, using polytetrafluoroethylene, a solid fluorine material, results in enhanced bacterial growth. Such solid materials can be easily isolated and reused for microbial culture, suggesting their potential as valuable technologies in food production and biotechnology.

Evaluation of Corrosion Performance of AZ31 Mg Alloy in Physiological and Highly Corrosive Solutions.

Resorbable Mg and Mg alloys have gained significant interest as promising biomedical materials. However, corrosion of these alloys can lead to premature reduction in their mechanical properties, and therefore their corrosion rate needs to be controlled. The aim of this study is to select an appropriate environment where the effects of coatings on the corrosion rate of the underlying Mg alloy can be discerned and measured in a relatively short time period. The corrosion resistance of uncoated AZ31 alloy in different solutions [Hank's Balanced Salt Solution, 1× phosphate buffered solution (PBS), 4× PBS, 0.9%, 3.5%, and 5 M sodium chloride (NaCl)] was determined by measuring the weight loss over a 2 week period. Upon exposure to physiological solutions, the uncoated AZ31 alloys exhibited a variable weight increase of 0.4 ± 0.4%. 3.5% and 5 M NaCl solutions led to 0.27 and 9.7 mm/year corrosion rates, respectively, where the compositions of corrosion products from AZ31 in all saline solutions were similar. However, the corrosion of the AZ31 alloy when coated by electrochemical oxidation with two phosphate coatings, one containing fluorine (PF) and another containing both fluorine and silica (PFS), showed 0.3 and 0.25 mm/year corrosion rates, respectively. This is more than 30 times lower than that of the uncoated alloy (7.8 mm/year), making them promising candidates for corrosion protection in severe corrosive environments. Cross-sections of the samples showed that the coatings protected the alloy from corrosion by preventing access of saline to the alloy surface, and this was further reinforced by corrosion products from both the alloy and the coatings forming an additional barrier. The information in this paper provides a methodology for evaluating the effects of coatings on the rate of corrosion of magnesium alloys.

Fluorine mass balance analysis in wild boar organs from the Bohemian Forest National Park.

Wild boars have been reported as bioindicators for per- and polyfluoroalkyl substances (PFAS) in a variety of studies. However, data about PFAS levels in wild boars from sites with limited industrial and general human activity is scarce. In this study, wild boar (Sus scrofa) organs from the Bohemian Forest National Park (Czech Republic) were used as bioindicators for PFAS pollution. In this work, 29 livers and 24 kidneys from 30 wild boars (0.5-5 years) were investigated using a fluorine mass balance approach. For this, the samples were measured using high performance liquid chromatography with electrospray ionisation tandem mass spectrometry (HPLC-ESI-MS/MS), targeting 30 PFAS, including legacy and replacement PFAS, direct total oxidisable precursor assay (dTOPA) and combustion ion chromatography (CIC). Perfluorocarboxylic acids (PFCAs) from C7 to C14 and perfluorooctanesulfonic acid (PFOS) were detected in >50 % of samples. In the livers, PFCAs dominated the profile with median concentrations of 230 µg/kg for perfluorononanoic acid (PFNA) and 75 µg/kg perfluorooctanoic acid (PFOA). PFOA and PFNA concentrations in the livers were one order of magnitude higher than in livers from wild boars caught in rural NE Germany considered as background concentration. PFOS in liver contributed only 30 % to the Σc(PFASTarget) with a median concentration of 170 µg/kg. Kidneys and livers contain an average of 2460 µg F/kg and 6800 µg F/kg extractable organic fluorine (EOF) respectively. Σc(PFASTarget) add up to a maximum of 10 % of the extractable organic fluorine. After oxidisation of the samples, PFOA, PFNA and Σc(PFASdTOPA) increased in livers, but could not explain the EOF. The elevated concentration of PFOA and PFNA may indicate differences in biomagnification for different habitats or an unidentified PFAS source in proximity to the national park.

The Pharmaceutical Industry in 2023: An Analysis of FDA Drug Approvals from the Perspective of Molecules.

With the COVID-19 pandemic behind us, the U.S. Food and Drug Administration (FDA) has approved 55 new drugs in 2023, a figure consistent with the number authorized in the last five years (53 per year on average). Thus, 2023 marks the second-best yearly FDA harvest after 2018 (59 approvals) in all the series. Monoclonal antibodies (mAbs) continue to be the class of drugs with the most approvals, with an exceptional 12, a number that makes it the most outstanding year for this class. As in 2022, five proteins/enzymes have been approved in 2023. However, no antibody-drug conjugates (ADCs) have been released onto the market. With respect to TIDES (peptides and oligonucleotides), 2023 has proved a spectacular year, with a total of nine approvals, corresponding to five peptides and four oligonucleotides. Natural products continue to be the best source of inspiration for drug development, with 10 new products on the market. Three drugs in this year's harvest are pegylated, which may indicate the return of pegylation as a method to increase the half-lives of drugs after the withdrawal of peginesatide from the market in 2013. Following the trends in recent years, two bispecific drugs have been authorized in 2023. As in the preceding years, fluorine and/or N-aromatic heterocycles are present in most of the drugs. Herein, the 55 new drugs approved by the FDA in 2023 are analyzed exclusively on the basis of their chemical structure. They are classified as the following: biologics (antibodies, proteins/enzymes); TIDES (peptide and oligonucleotides); combined drugs; pegylated drugs; natural products; nitrogen aromatic heterocycles; fluorine-containing molecules; and other small molecules.

Biomimetic ZrO2-modified seaweed residue with excellent fluorine/ bacteria removal and uranium extraction properties for wastewater purification.

Exploring and developing promising biomass composite membranes for the water purification and waste resource utilization is of great significance. The modification of biomass has always been a focus of research in its resource utilization. In this study, we successfully prepare a functional composite membrane, activated graphene oxide/seaweed residue-zirconium dioxide (GOSRZ), with fluoride removal, uranium extraction, and antibacterial activity by biomimetic mineralization of zirconium dioxide nanoparticles (ZrO2 NPs) on seaweed residue (SR) grafted with oxidized graphene (GO). The GOSRZ membrane exhibits highly efficient and specific adsorption of fluoride. For the fluoride concentrations in the range of 100-400 mg/L in water, the removal efficiency can reach over 99 %, even in the presence of interfering ions. Satisfactory extraction rates are also achieved for uranium by the GOSRZ membrane. Additionally, the antibacterial performance studies show that this composite membrane efficiently removes Escherichia coli (E. coli) and Methicillin-resistant Staphylococcus aureus (MRSA). The high adsorption of F- and U(VI) to the composite membrane is ascribed to the ionic exchange and coordination interactions, and its antibacterial activity is caused by the destruction of bacterial cell structure. The sustainability of the biomass composite membranes is further evaluated using the Sustainability Footprint method. This study provides a simple preparation method of biomass composite membrane, expands the water purification treatment technology, and offers valuable guidance for the resource utilization of seaweed waste and the removal of pollutants in wastewater.

Controlling the incorporation of fluorinated amino acids in human cells and its structural impact.

Fluorinated aromatic amino acids (FAAs) are promising tools when studying protein structure and dynamics by NMR spectroscopy. The incorporation FAAs in mammalian expression systems has been introduced only recently. Here, we investigate the effects of FAAs incorporation in proteins expressed in human cells, focusing on the probability of incorporation and its consequences on the 19 F NMR spectra. By combining 19 F NMR, direct MS and x-ray crystallography, we demonstrate that the probability of FAA incorporation is only a function of the FAA concentration in the expression medium and is a pure stochastic phenomenon. In contrast with the MS data, the x-ray structures of carbonic anhydrase II reveal that while the 3D structure is not affected, certain positions lack fluorine, suggesting that crystallization selectively excludes protein molecules featuring subtle conformational modifications. This study offers a predictive model of the FAA incorporation efficiency and provides a framework for controlling protein fluorination in mammalian expression systems.

"Fluorine Effects" in Conformational Orchestration of α/ß Hybrid Peptide with a 9-membered Pseudo ß-Turn Motif.

Fluorine, the tiny robust atom, with its unique features has captured the attention of scientists in recent times, especially in drug discovery with its integration in small molecules, peptides, and proteins. However, studies to understand the 'fluorine effects' on the conformation of molecules that follow 'beyond the rule of 5' are in the infancy yet significant in molecular design and function. For the first time, using short hybrid peptide sequence as an appropriate model, we examined the substitution effect (size, stereoelectronic effect, and hydrogen bonding) using X-ray diffraction, 2D-NMR, and CD studies. The comparative study on their folding patterns with hydrogen-substituted analogs can provide valuable insights into fluorinated substrates' design.

Structural dependence of PFAS oxidation in a boron doped diamond-electrochemical system.

Driven by long-term persistence and adverse health impacts of legacy perfluorooctanoic acid (PFOA), production has shifted towards shorter chain analogs (C4, perfluorobutanoic acid (PFBA)) or fluorinated alternatives such as hexafluoropropylene oxide dimer acid (HFPO-DA, known as GenX) and 6:2 fluorotelomer carboxylic acid (6:2 FTCA). Yet, a thorough understanding of treatment processes for these alternatives is limited. Herein, we conducted a comprehensive study using an electrochemical approach with a boron doped diamond anode in Na2SO4 electrolyte for the remediation of PFOA common alternatives, i.e., PFBA, GenX, and 6:2 FTCA. The degradability, fluorine recovery, transformation pathway, and contributions from electro-synthesized radicals were investigated. The results indicated the significance of chain length and structure, with shorter chains being harder to break down (PFBA (65.6 ± 5.0%) < GenX (84.9 ± 3.3%) < PFOA (97.9 ± 0.1%) < 6:2 FTCA (99.4 ± 0.0%) within 120 min of electrolysis). The same by-products were observed during the oxidation of both low and high concentrations of parent PFAS (2 and 20 mg L-1), indicating that the fundamental mechanism of PFAS degradation remained consistent. Nevertheless, the ratio of these by-products to the parent PFAS concentration varied which primarily arises from the more rapid PFAS decomposition at lower dosages. For all experiments, the main mechanism of PFAS oxidation was initiated by direct electron transfer at the anode surface. Sulfate radical (SO4•-) also contributed to the oxidation of all PFAS, while hydroxyl radical (•OH) only played a role in the decomposition of 6:2 FTCA. Total fluorine recovery of PFBA, GenX, and 6:2 FTCA were 96.5%, 94.0%, and 76.4% within 240 min. The more complex transformation pathway of 6:2 FTCA could explain its lower fluorine recovery. Detailed decomposition pathways for each PFAS were also proposed through identifying the generated intermediates and fluorine recovery. The proposed pathways were also assessed using 19F Nuclear Magnetic Resonance (NMR) spectroscopy.

Next-Generation Tags for Fluorine Nuclear Magnetic Resonance: Designing Amplification of Chemical Shift Sensitivity.

Fluorine NMR is a highly sensitive technique for delineating the conformational states of biomolecules and has shown great utility in drug screening and in understanding protein function. Current fluorinated protein tags leverage the intrinsic chemical shift sensitivity of the 19F nucleus to detect subtle changes in protein conformation and topology. This chemical shift sensitivity can be amplified by embedding the fluorine or trifluoromethyl reporter within a pyridone. Due to their polarizability and rapid tautomerization, pyridones exhibit a greater range of electron delocalization and correspondingly greater 19F NMR chemical shift dispersion. To assess the chemical shift sensitivity of these tautomeric probes to the local environment, 19F NMR spectra of all possible monofluorinated and trifluoromethyl-tagged versions of 2-pyridone were recorded in methanol/water mixtures ranging from 100% methanol to 100% water. 4-Fluoro-2-pyridone and 6-(trifluoromethyl)-2-pyridone (6-TFP) displayed the greatest sensitivity of the monofluorinated and trifluoromethylated pyridones, exceeding that of known conventional CF3 reporters. To evaluate the utility of tautomeric pyridone tags for 19F NMR of biomolecules, the alpha subunit of the stimulatory G protein (Gsα) and human serum albumin (HSA) were each labeled with a thiol-reactive derivative of 6-TFP and the spectra were recorded as a function of various adjuvants and drugs. The tautomeric tag outperformed the conventional tag, 2-bromo-N-(4-(trifluoromethyl)phenyl)acetamide through the improved resolution of several functional states.