Search

A new concept for the synthesis of dialkyl chloronium cations [R−Cl−R]+ is described (R=CH3, CH2CF3), that allows the formation of fluorinated derivatives. By utilizing the xenonium salt [XeOTeF5][M(OTeF5)n] (M=Sb, n=6; M=Al, n=4) chlorine atoms of chloroalkanes or the deactivated chlorofluoroalkane CH2ClCF3 are oxidized and removed as ClOTeF5 leading to the isolation of the corresponding chloronium salt. Since the resulting highly electrophilic cation [Cl(CH2CF3)2]+ is able to alkylate weak nucleophiles, this compound can be utilized for the introduction of a fluorinated alkyl group to those. In addition, the fluorinated alkyl chloronium cation displays a high hydride ion affinity, enabling the activation of linear hydrocarbons by hydride abstraction even at low temperatures ultimately leading to the formation of branched carbocations. [ABSTRACT FROM AUTHOR]

A practical and efficient trifluoromethylation of readily available and bench stable N‐Thiophthalimides and N‐Thioimides with Ruppert‐Prakash reagent (TMS‐CF3) is described. The reaction proceeds at room temperature and only requires NaOAc as the mild promoter to prepare a series of trifluoromethyl thioethers in good to excellent yields. Both aryl and alkyl derivates are well trifluoromethylated under transition‐metal‐free reaction conditions. Moreover, the reaction features with scale‐up synthesis and late‐stage modification of bioactive molecule. [ABSTRACT FROM AUTHOR]

Fluoroalkyl ketones are a class of structural motifs which are ubiquitous in bioactive molecules, and serve as synthons for diverse value‐added fluorine‐containing targets. The presence of fluorine significantly alters the lipophilicity and bioactivity of alkyl ketones as well as imposes additional challenges on the synthesis of fluoroalkyl ketones. Traditional methods for the synthesis of fluoroalkyl ketones heavily rely on multiple‐step manipulations which require stoichiometric reagents and suffer from low efficiency. Thus, the development of synthesizing fluoroalkyl ketones enabled by catalytic methods is highly valuable yet challenging. This Concept summarizes the recent renaissance in developing catalytic methods for the synthesis of fluoroalkyl ketones with diverse substitution patterns from different fluorine‐containing precursors. In addition, further efforts for catalytic method development are also discussed. [ABSTRACT FROM AUTHOR]

The structure of cis‐ or trans‐bridged [GeF5]− anionic chains have been investigated [Mallouk et al. (1984). Inorg. Chem.23, 3160–3166] showing the first crystal structures of μ‐F‐bridged pentafluorogermanates. Herein, we report the second crystal structure of trans‐pentafluorogermanate anions present in the crystal structure of sodium trans‐pentafluorogermanate(IV) bis(hydrogen fluoride), Na[GeF5]·2HF. The crystal structure [orthorhombic Pca21, a = 12.3786 (3), b = 7.2189 (2), c = 11.4969 (3) Å and Z = 8] is built up from infinite chains of trans‐linked [GeF6]2− octahedra, extending along the b axis and spanning a network of pentagonal bipyramidal distorted Na‐centred polyhedra. These [NaF7] polyhedra are linked in a trans‐edge fashion via hydrogen fluoride molecules, in analogy to already known sodium hydrogen fluorides and potassium hydrogen fluorides. [ABSTRACT FROM AUTHOR]

The reactivity of carbamoyl radicals, generated in situ from sodium oxamate salts, has been investigated in the context of radical carbofluorination reactions of olefins and α‐fluoroolefins, respectively. Both transformations are catalyzed by silver salts and required the presence of potassium persulfate (K2S2O8) and SelectfluorTM as a radicophilic fluorine source. The reported methods provide a direct access to β‐fluoroamides and β,β‐difluoroamides. [ABSTRACT FROM AUTHOR]

The fluoroalkoxy groups (ORf) are widely used motifs in pharmaceutical and agrochemical fields due to their unique physicochemical properties including higher lipophilicity and increased metabolic stability. Thus, the high value of ORf‐containing derivatives has stimulated the development of fluoroalkoxylation reactions. In this review, we highlight the recent progress of various trifluoroalkoxylating reagents and their applications in organic synthesis in the past five years. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The development of switchable solvent‐free multicomponent reactions to build high‐value‐added products is an important demand for organic synthesis. Herein, we detailed the successful implementation of a switchable strategy for the construction of diverse 4‐fluoroalkyl‐1,4‐dihydropyrimidines and 4‐fluoroalkyl‐pyrimidines via a solvent/additive‐free [3 + 2 + 1] annulation, starting from readily available enamines, trifluoroacetaldehyde hydrate or 1‐ethoxy‐2,2‐difluoroethanol and amidines hydrochloride. This reaction conforms to the concept of green synthesis, and provides a new avenue to access valuable fluorinated heterocycles. [ABSTRACT FROM AUTHOR]

Herein we report a general access to silver(i) perfluoroalcoholates, their structure in the solid state and in solution, and their use as transfer reagents. The silver(i) perfluoroalcoholates are prepared by the reaction of AgF with the corresponding perfluorinated carbonyl compounds in acetonitrile and are stable for a prolonged time at −18 °C. X‐ray analysis of single crystals of perfluoroalcoholate species showed that two Ag(i) centers are bridged by the alcoholate ligands. In acetonitrile solution, Ag[OCF3] forms different structures as indicated by IR spectroscopy. Furthermore, the silver(i) perfluoroalcoholates can be used as easy‐to‐handle transfer reagents for the synthesis of Cu[OCF3], Cu[OC2F5], [PPh4][Au(CF3)3(OCF3)], and fluorinated alkyl ethers. [ABSTRACT FROM AUTHOR]

Anhydrous hydrogen fluoride (AHF), a critical raw material for industries such as aluminum, pharmaceuticals, and petroleum, has traditionally been sourced from fluorite--a non-renewable mineral. The unsustainable reliance on fluorite has catalyzed the search for alternative AHF production methods. A promising substitute is fluorosilicic acid (FSA), a byproduct of the phosphate fertilizer industry previously deemed waste. Transforming fluorosilicic acid into AHF not only yields a valuable resource but also addresses the environmental and economic challenges associated with waste management. The innovative practice of producing AHF from fluorosilicic acid signals a shift towards sustainable chemical production by capitalizing on waste, potentially diminishing reliance on fluorite and reducing the industry's environmental impact. This review thoroughly dissects the AHF synthesis process from fluorosilicic acid. Despite the acknowledged importance of fluorinated compounds in numerous industrial applications, research on their synthesis from fluorosilicic acid is limited and fragmented. This review seeks to amalgamate this scattered information by closely scrutinizing diverse industrial processing methods. Additionally, it explores the current and future landscape, economic feasibility, and strategies to navigate the obstacles inherent in synthesizing AHF from fluorosilicic acid. It also assesses the environmental impact of these methods, thereby contributing to the dialogue in this emerging field. The primary aim of this manuscript is to foster further research and promote the industrial uptake of this sustainable process. Highlighting the challenges and proposing potential improvements, the review supports the responsible reuse of waste and advocates for advancements in industrial practices. [ABSTRACT FROM AUTHOR]

Given the profound effect of fluorine‐containing groups in improving the chemical, physical, and biological properties of the parent compound, the fluorine‐containing groups were receiving increasing attention in the medicinal, pharmaceutical, agricultural, and material sciences. Unlike well‐developed trifluoromethylation and difluoromethylation reactions, the efficient and mild methods for rapid introduction of CF2Me are still underdeveloped, despite their important applications in pharmaceuticals and agrochemicals. This concept describes recent progress in difluoroethylation functionalization. [ABSTRACT FROM AUTHOR]

[Display omitted] • Difluoromethyl ketones are tools and more recently leads in drug discovery. • The metabolic stability of difluoromethyl ketones is generally uncharacterized. • Thirty-nine β-amino and β-hydroxy difluoromethyl ketones were synthesized. • Structure–stability studies in rodent serum and liver microsomes were conducted. Although difluoromethyl ketones are used as tools in chemical biology and leads in drug discovery, the metabolic stability of these compounds is generally uncharacterized and must be inferred from in vivo pharmacological assays. In order to address this gap which impedes their wider use, we have synthesized and performed metabolic stability studies for thirty-nine β-amino and β-hydroxy difluoromethyl ketones. These investigations provide structure–stability relationships of the difluoromethyl ketones following incubation with rodent serum and liver microsomes. [ABSTRACT FROM AUTHOR]

• This review summarized fluorine chemistry with a flow reactor. • We categorized organometallic reactions, electrochemistry, photochemistry, gas-liquid reactions, heterogeneous reactions and 18F-fluorination. • An efficient strategy for using flow systems to access complex fluorine-containing molecules. Organofluorine compounds have proven to play an important role in pharmaceutical, agrochemical, and functional materials owing to their unique properties. However, the synthesis of these compounds is often challenging due to the difficulties in handling fluorinating agents and controlling their reactivity precisely. Recently, flow microreactor systems have attracted significant attention from chemists as a highly efficient synthetic methodology. In this review, we summarize recent advances in fluorine chemistry facilitated by continuous flow technology, highlighting its advantages and potential applications in streamlined synthesis of organofluorine compounds. [Display omitted] [ABSTRACT FROM AUTHOR]

In this work, we developed soft and highly stable perfluorocarbon-free foams based on cellulose nanofibres (CNFs), cellulose nanocrystals (CNCs) and alkyl polyglycoside (APG). Neither the CNCs nor the CNFs can effectively stabilise the APG foam, which is reflected in the spontaneous degradation of the foam. Interestingly, blending these two nanocelluloses and foaming resulted in an ultrastable foam. The reflective optical interference technique was used to visualise liquid flow in the liquid film, and the results showed that the foam film with a thickness of only a few tens of nanometres gained excellent mechanical stability by tuning the assembly of CNCs and CNFs at the air-liquid interface. Moreover, the interfibril interactions at the Plateau borders reduce the bubble coarsening rate and drainage rate. In pool fire extinguishing tests, increasing the total concentration of CNCs and CNFs improved the foam stability, but increasing the viscosity led to a decrease in the foam spreading rate. Thus, a formulation with 0.4 % nanocellulose has poorer firefighting performance than a formulation with 0.15 % nanocellulose. When the ratios of CNCs and CNFs are properly controlled, the burnback performance of perfluorocarbon-free foam is better than that of state-of-the-art fluorinated AFFFs for n-heptane pool fires. The sustainability of the firefighting process is considerably improved by switching to the nonperfluorinated liquid foam developed in this work., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The aqueous photolysis of four pharmaceuticals with varying fluorinated functional groups was assessed under neutral, alkaline, advanced oxidation, and advanced reduction conditions with varying light sources. Solar simulator quantum yields were 2.21 × 10 -1  mol Ei -1 for enrofloxacin, 9.36 × 10 -3  mol Ei -1 for voriconazole, and 1.49 × 10 -2  mol Ei -1 for flecainide. Florfenicol direct photolysis was slow, taking 150 h for three degradation half-lives. Bimolecular rate constants between pharmaceuticals and hydroxyl radicals were 10 9 to 10 10  M -1  s -1 . Using a combined quantitative fluorine nuclear magnetic resonance spectroscopy ( 19 F-NMR) and mass spectrometry approach, fluorine mass balances and photolysis product structures were elucidated. Enrofloxacin formed a variety of short-lived fluorinated intermediates that retained the aryl F motif. Extended photolysis time led to complete aryl F mineralization to fluoride. The aliphatic F moiety on florfenicol was also mineralized to fluoride, but the resulting product was a known antibiotic (thiamphenicol). For voriconazole, the two aryl Fs contributed more to fluoride production compared with the heteroaromatic F, indicating higher stability of the heteroaromatic F motif. The two aliphatic CF 3 moieties in the flecainide structure remained intact under all conditions, further supporting the stability of these moieties found in per- and polyfluoroalkyl substances under a variety of conditions. The advanced treatment conditions generating hydroxyl radicals or hydrated electrons accelerated the degradation, but not the defluorination, of flecainide. The combination of 19 F-NMR and mass spectrometry proved powerful in allowing identification of fluorinated products and verifying the functional groups present in the intermediates and products. The results found in the present study will aid in the understanding of which fluorinated functional groups should be incorporated into pharmaceuticals to ensure organofluorine byproducts are not formed in the environment and help determine the water-treatment processes that effectively remove specific pharmaceuticals and more generally fluorinated motifs. Environ Toxicol Chem 2024;43:2285-2296. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC., (© 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.)

19 F electron-nuclear double resonance (ENDOR) has emerged as an attractive method for determining distance distributions in biomolecules in the range of 0.7-2 nm, which is not easily accessible by pulsed electron dipolar spectroscopy. The 19 F ENDOR approach relies on spin labeling, and in this work, we compare various labels' performance. Four protein variants of GB1 and ubiquitin bearing fluorinated residues were labeled at the same site with nitroxide and trityl radicals and a Gd(III) chelate. Additionally, a double-histidine variant of GB1 was labeled with a Cu(II) nitrilotriacetic acid chelate. ENDOR measurements were carried out at W-band (95 GHz) where 19 F signals are well separated from 1 H signals. Differences in sensitivity were observed, with Gd(III) chelates providing the highest signal-to-noise ratio. The new trityl label, OXMA, devoid of methyl groups, exhibited a sufficiently long phase memory time to provide an acceptable sensitivity. However, the longer tether of this label effectively reduces the maximum accessible distance between the 19 F and the C α of the spin-labeling site. The nitroxide and Cu(II) labels provide valuable additional geometric insights via orientation selection. Prediction of electron-nuclear distances based on the known structures of the proteins were the closest to the experimental values for Gd(III) labels, and distances obtained for Cu(II) labeled GB1 are in good agreement with previously published NMR results. Overall, our results offer valuable guidance for selecting optimal spin labels for 19 F ENDOR distance measurement in proteins.

We explore the potential of fluorine-containing small Mn 2+ chelates as alternatives to perfluorinated nanoparticles, widely used as 19 F MRI probes. In MnL1, the cyclohexanediamine skeleton and two piperidine rings, involving each a metal-coordinating amide group and an appended CF 3 moiety, provide high rigidity to the complex. This allows for good control of the Mn-F distance (r MnF =8.2±0.2 Å determined from 19 F relaxation data), as well as for high kinetic inertness (a dissociation half-life of 1285 h is estimated for physiological conditions). The paramagnetic Mn 2+ leads to a ~150-fold acceleration of the longitudinal 19 F relaxation, with moderate line-broadening effect, resulting in T 2 /T 1 ratios of 0.8 (9.4 T). Owing to its inner sphere water molecule, MnL1 is a good 1 H relaxation agent as well (r 1 =5.36 mM -1  s -1 at 298 K, 20 MHz). MnL1 could be readily visualized in 19 F MRI by using fast acquisition techniques, both in phantom images and living mice following intramuscular injection, with remarkable signal-to-noise ratios and short acquisition times. While applications in targeted imaging or cell therapy monitoring require further optimisation of the molecular structure, these results argue for the potential of such small, monohydrated and fluorinated Mn 2+ complexes for combined 19 F and 1 H MRI detection., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Multimodal imaging probes play a crucial role in overcoming the limitations associated with single-mode imaging for clinical medical diagnosis. This study focuses on the development of a photoresponsive fluorine-containing water-soluble polymer ( PF ) through RAFT polymerization. Subsequently, a polymer-gadolinium(III) hybrid ( PF-Gd ) dual-modal probe capable of T 1 -weighted 1 H MRI and 19 F MRI was synthesized via postmodification of PF with a Gd-DOTA derivative. Under physiological conditions (pH = 7.4), the hybrids exhibit UV-activated 19 F NMR/MRI and enhanced 1 H MRI. The inclusion of Gd 3+ facilitates the acceleration of water molecule T 1 relaxation, leading to high-intensity 1 H MRI contrast. Leveraging the paramagnetic relaxation enhancement (PRE) effect between fluorine atoms and Gd 3+ , the restoration of Gd 3+ -accelerated 19 F T 2 relaxation enables precise photoactivation of 19 F MRI signals, transitioning from the "OFF" to the "ON" state. This study provides an important reference for the development of hybrid systems that function as real-time diagnostic tools and offers controlled activation for multimodal imaging probes.

Fluorine possesses distinctive chemical characteristics, such as its strong electron-withdrawing ability and small atomic size, which render it an invaluable asset in the design and optimization of pharmaceuticals. The utilization of fluorine-enriched medications for combating cancer has emerged as a prominent approach in medicinal chemistry and drug discovery, offering improved clinical outcomes and enhanced pharmacological properties. This comprehensive review explores the synthetic approaches and clinical applications of approved 22 representative fluorinated anti-cancer drugs from 2019 to present, shedding light on their historical development, brand names, drug target activity, mechanism of action, preclinical pharmacodynamics, clinical efficacy, and toxicity. Additionally, the review provides an extensive analysis of the representative synthetic techniques employed. Overall, this review emphasizes the significance of incorporating fluorine chemistry into anti-cancer drug research while highlighting promising future prospects for exploring compounds enriched with fluorine in the battle against cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Obtaining atomic-level information on components in the cell is a major focus in structural biology. Elucidating specific structural and dynamic features of proteins and their interactions in the cellular context is crucial for understanding cellular processes. We introduce 19 F dynamic nuclear polarization (DNP) combined with fast magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy as a powerful technique to study proteins in mammalian cells. We demonstrate our approach on the severe acute respiratory syndrome coronavirus 2 5F-Trp-N NTD protein, electroporated into human cells. DNP signal enhancements of 30- to 40-fold were observed, translating into over 1000-fold experimental time savings. High signal-to-noise ratio spectra were acquired on nanomole quantities of a protein in cells in minutes. 2D 19 F- 19 F dipolar correlation spectra with remarkable sensitivity and resolution were obtained, exhibiting 19 F- 19 F cross peaks associated with fluorine atoms as far as ~10 angstroms apart. This work paves the way for 19 F DNP-enhanced MAS NMR applications in cells for probing protein structure, dynamics, and ligand interactions.

The membrane fouling derived from the accumulated dust pollutants and highly viscous oily particles causes irreversible damage to the filtration performance of air filters and results in a significant reduction in their service life. However, it is still challenging to construct high-efficiency and antifouling air filtration membranes with recyclable regeneration. Herein, the fluorine-free amphiphobic micro/nanofiber composite membrane was controllably constructed by integrating click chemistry reaction and electrospinning technique. Low-surface-energy fibers were constructed by a thiol-ene click chemical reaction between mercaptosilane and vinyl groups of polystyrene-butadiene-styrene (SBS), combined with hydroxyl-terminated poly(dimethylsiloxane) during the electrospinning process. The functional air filter is then prepared by the two-layer composite strategy. Because of the advantages of liquid-like fibrous surface and micro/nanofibrous porous structure, SBS/PAN composite membrane simultaneously shows superior antifouling performances of pollutants and filtration efficiency of over 97% PM 0.3 removal. More importantly, the antifouling fibrous membrane still presents a stable and efficient filtration efficiency after multiple washes. Its service life in dust filtration environments is approximately 1.7 times longer than that of the substrate membrane. This work may provide a significant reference for the design of antifouling fiber membranes and high-efficiency air filters with long life spans and reusability.

Significant progress has been made in developing fluorine-free firefighting foams (F3) as alternatives to perfluoroalkyl substances (PFAS)-containing aqueous film-forming foams (AFFF) to help eliminate the health and environmental concerns linked to PFAS exposure. However, developing viable F3 options hinges on a thorough assessment of potential risks alongside the technical performance evaluations. This study showcases the capability of a zebrafish-based platform to discern the developmental and behavioral toxicities associated with exposure to one AFFF and two F3 formulations. To facilitate direct exposure to the chemicals, embryos were enzymatically dechorionated and then exposed to the diluted formulations (6-120 hours post fertilization (hpf)) at concentrations folding from 0.1% of the manufacturer-recommended working concentrations. The exposure regimen also included daily automated media changes (50%) and mortality assessments (24 and 120 hpf). At 120 hpf, a comprehensive assessment encompassing overall development, prevalence of morphological defects, and behavioral responses to acute stressors (visual, acoustic, and peripheral irritant) was conducted. Exposure to both F3s significantly increased larval mortalities to percentages exceeding 90%, whereas AFFF exposures did not cause any significant effect. Overall development, marked by total larval length, was significantly impacted following exposures to all foams. Behavioral responses to acute stressors were also significantly altered following exposures to both F3s, whereas the AFFF did not alter behavior at the concentrations tested. Our findings demonstrate toxicities associated with tested F3 formulations that encompass several endpoints and highlight the utility of the proposed platform in evaluating the developmental toxicities of current and future foam formulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

By integrating TiO 2 with rare earth upconversion nanocrystals (NaREF 4 ), efficient energy transfer can be achieved between the two subunits under near-infrared (NIR) excitation, which hold tremendous potential in the fields of photocatalysis, photodynamic therapy (PDT), etc. However, in the previous studies, the combination of TiO 2 with NaREF 4 is a non-epitaxial random blending mode, resulting in a diminished energy transfer efficiency between the NaREF 4 and TiO 2 . Herein, we present a fluorine doping-mediated epitaxial growth strategy for the synthesis of TiO 2 -NaREF 4 heteronanocrystals (HNCs). Due to the epitaxial growth connection, NaREF 4 can transfer energy through phonon-assisted pathway to TiO 2 , which is more efficient than the traditional indirect secondary photon excitation. Additionally, F doping brings oxygen vacancies in the TiO 2 subunit, which further introduces new impurity energy levels in the intrinsic band gap of TiO 2 subunit, and facilitates the energy transfer through phonon-assisted method from NaREF 4 to TiO 2 . As a proof of concept, TiO 2 -NaGdF 4  : Yb,Tm@NaYF 4 @NaGdF 4  : Nd@NaYF 4 HNCs were rationally constructed. Taking advantage of the dual-model up- and downconversion luminescence of the delicately designed multi-shell structured NaREF 4 subunit, highly efficient photo-response capability of the F-doped TiO 2 subunit and the efficient phonon-assisted energy transfer between them, the prepared HNCs provide a distinctive nanoplatform for bioimaging-guided NIR-triggered PDT., (© 2024 Wiley-VCH GmbH.)

Triclosan (TCS), triclocarban (TCC), and chlorophenols (CPs) are broad-spectrum antibacterials widely used in dermatological and oral hygiene products, which could induce severe liver and intestine injuries. Hence, it is essential to establish a rapid and sensitive method to monitor TCS, TCC, and CPs in various organisms. In this work, fluorine-functionalized covalent organic framework (COF-F) was prepared by using 4,4',4''-(1,3,5-triazine-2,4,6-triyl)tri-aniline and 2,3,5,6-tetrafluoroterephthalaldehyde as two building units and employed as a solid phase microextraction (SPME) probe for the extraction of TCS, TCC and CPs. The COF-F possessed excellent hydrophobicity, a large specific surface area (1354.3 m 2  g -1 ) and high uniform porosity (3.2 nm), which facilitated high selectivity and adsorption properties towards TCS, TCC, and CPs. Therefore, the as-prepared COF-F-SPME in combination with electrospray ionization mass spectrometry has been developed to provide fast and ultrasensitive detection of TCS, TCC, and CPs in biological samples. The established method demonstrated satisfactory linear ranges (0.01-100.00 μg L -1 ) and low limits of detection (0.003-0.040 μg L -1 ) for TCS, TCC and CPs. The developed method could be successfully applied to detect TCS, TCC and CPs in the liver and kidney tissues of mice, demonstrating the potential for the detection of chlorinated aromatic pollutants in the biological samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The novel donor-acceptor (D-A) type covalent organic frameworks TATF-COF and TATP-COF, with multiple fluorine groups as electron storage units, were successfully constructed to achieve efficient charge transfer and photocatalytic activity for antibacterial photocatalytic therapy. Fluorine, the most electronegative element, was utilized as an electron-withdrawing substituent for the acceptor, which could unite the donor unit together and efficiently improve the charge transfer from the donor to acceptor. The unique D-A structures of TATF-COF and TATP-COF ensure that they have narrow band gaps, strong photocurrent responses, long fluorescence lifetimes, and good capacity to generate reactive oxygen species (ROS) to realize good antibacterial activity. Meanwhile, the inclusion of multiple hydrophilic fluorine groups means that TATF-COF and TATP-COF are highly water dispersible, which is also beneficial in terms of promoting the generation of adequate quantities of ROS. Hence, in view of their excellent photoelectric properties and good water dispersibility, further investigations were performed, and excellent antibacterial activities in vitro against both gram-negative and gram-positive bacteria were demonstrated for TATF-COF and TATP-COF. In addition, we also showed that they can function as effective antibacterial dental materials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A variable or non-stoichiometric hydrate of GDC-4379 was developed into a formulated capsule with a 1% drug loading. The water content of this hydrate varied from 0-0.7 moles over the relative humidity (RH) range of 0-98% (25°C). Since a variable state of hydration coupled with rapid equilibration of lattice water with the environmental RH can lead to challenges in formulation development, an analytical method to directly and accurately determine the state of hydration of the active in such a low dose formulation was deemed necessary. Owing to its high selectivity and fast acquisition times, 19 F solid-state NMR was effectively utilized to directly determine the lattice water content of the active in the formulated capsule. By correlating Δδ, the chemical shift difference between the isotropic peaks, with the relative humidity and ultimately the lattice water content, the state of hydration of GDC-4379 in the formulated capsule was experimentally determined as 0.63 moles of water/mole of anhydrate., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paroma Chakravarty, Joe Lubach, Antonio DiPasquale, Jonathan Hau reports a relationship with Genentech USA Inc South San Francisco that includes: employment and equity or stocks. None If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Magnetic resonance imaging (MRI) relies on appropriate contrast agents, especially for visualizing transplanted cells within host tissue. In recent years, compounds containing fluorine-19 have gained significant attention as MRI probe, particularly in dual 1 H/ 19 F-MR imaging. However, various factors affecting probe sensitivity, such as fluorine content and the equivalency of fluorine atoms, must be considered. In this study, we synthesized fluorinated micelles with adjustable surface positive charge density and investigated their physicochemical properties and MRI efficacy in phantoms and labeled cells. While the micelles exhibited clear signals in 19 F-MR spectra and imaging, the concentrations required for MRI visualization of labeled cells were relatively high, adversely affecting cell viability. Despite their favourable physicochemical properties, achieving higher labeling rates without compromising cell viability during labeling remains a challenge for potential in vivo applications., (© 2024. The Author(s).)

The Lewis superacid Ga(OTeF 5 ) 3 has been synthesized and characterized, revealing a monomeric structure in solution and a dimeric structure in the solid state. Isolated adducts of Ga(OTeF 5 ) 3 with strong and weak Lewis bases have been characterized spectroscopically as well as by single-crystal X-ray diffractometry. The Lewis acidity of this new species has been evaluated by means of different experimental and theoretical methods, which has allowed to classify it as one of only a few examples of a gallium-based Lewis superacid. The high Lewis acidity of Ga(OTeF 5 ) 3 was used to amplify the strength of the Brønsted acid HOTeF 5 , leading to the protonation of diethyl ether. Furthermore, Ga(OTeF 5 ) 3 was utilized to access the strong oxidizing system Ga(OTeF 5 ) 3 /Xe(OTeF 5 ) 2 in SO 2 ClF, which was successfully employed in the synthesis of the dimethyl chloronium salt [Cl(CH 3 ) 2 ][Ga(OTeF 5 ) 4 ], a strong electrophilic methylation reagent., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

This study investigates the immobilization of cyanobacterial photosystem I (PSI) from Synechocystis sp. PCC 6803 onto fluorine-doped tin oxide (FTO) conducting glass plates to create photoelectrodes for biohybrid solar cells. The fabrication of these PSI-FTO photoelectrodes is based on two immobilization processes: rapid electrodeposition driven by an external electric field and slower adsorption during solvent evaporation, both influenced by gravitational sedimentation. Deposition and performance of photoelectrodes was investigated by UV-Vis absorption spectroscopy and photocurrent measurements. We investigated the efficiency of PSI immobilization under varying conditions, including solution pH, applied electric field intensity and duration, and electrode polarization, with the goals to control (1) the direction of migration and (2) the orientation of the PSI particles on the substrate surface. Variation in the pH value of the PSI solution alters the surface charge distribution, affecting the net charge and the electric dipole moment of these proteins. Results showed PSI migration to the positively charged electrode at pH 6, 7, and 8, and to the negatively charged electrode at pH 4.4 and 5, suggesting an isoelectric point of PSI between 5 and 6. At acidic pH, the electrophoretic migration was largely hindered by protein aggregation. Notably, photocurrent generation was consistently cathodic and correlated with PSI layer thickness, and no conclusions can be drawn on the orientation of the immobilized proteins. Overall, these findings suggest mediated electron transfer from FTO to PSI by the used electrolyte containing 10 mM sodium ascorbate and 200 μM dichlorophenolindophenol.

19 F magnetic resonance imaging ( 19 F MRI) is gaining attention as an emerging diagnostic technology. Effective 19 F MRI contrast agents (CAs) for in vivo applications require a long transverse (or spin-spin) relaxation time ( T 2 ), short longitudinal (or spin-lattice) relaxation time ( T 1 ), high fluorine content, and excellent biocompatibility. Here, we present a novel hyperbranched polymeric 19 F MRI CA based on β-cyclodextrin and phosphorylcholine. The influence of the branching degree and fluorine content on T 2 was thoroughly investigated. Results demonstrated a maximum fluorine content of 11.85% and a T 2 of 612 ms. This hyperbranched polymeric 19 F MRI CA exhibited both great biocompatibility against cells and organs of mice and high-performance imaging capabilities both in vitro and in vivo. The research provides positive insights into the synthesis strategies, topological design, and selection of fluorine tags for 19 F MRI CAs.

Fluorine magnetic resonance imaging ( 19 F MRI) is a rapidly evolving research area with a high potential to advance the field of clinical diagnostics. In this review, we provide an overview of the recent progress in the field of fluorinated stimuli-responsive polymers applied as 19 F MRI tracers. These polymers respond to internal or external stimuli (e.g., temperature, pH, oxidative stress, and specific molecules) by altering their physicochemical properties, such as self-assembly, drug release, and polymer degradation. Incorporating noninvasive 19 F labels enables us to track the biodistribution of such polymers. Furthermore, by triggering polymer transformation, we can induce changes in 19 F MRI signals, including attenuation, amplification, and chemical shift changes, to monitor alterations in the environment of the tracer. Ultimately, this review highlights the emerging potential of stimuli-responsive fluoropolymer 19 F MRI tracers in the current context of polymer diagnostics research.

Ligand binding hotspots are regions of protein surfaces that form particularly favourable interactions with small molecule pharmacophores. Targeting interactions with these hotspots maximises the efficiency of ligand binding. Existing methods are capable of identifying hotspots but often lack assays to quantify ligand binding and direct elaboration at these sites. Herein, we describe a fragment-based competitive 19 F Ligand Based NMR (LB-NMR) screening platform that enables routine, quantitative ligand profiling focused at ligand-binding hotspots. As a proof of concept, the method was applied to 4'-phosphopantetheine adenylyltransferase (PPAT) from Mycobacterium abscessus (Mabs). X-ray crystallographic characterisation of the hits from a 960-member fragment screen identified three ligand-binding hotspots across the PPAT active site. From the fragment hits a collection of 19 F reporter candidates were designed and synthesised. By rigorous prioritisation and use of optimisation workflows, a single 19 F reporter molecule was generated for each hotspot. Profiling the binding of a set of structurally characterised ligands by competitive 19 F LB-NMR with this suite of 19 F reporters recapitulated the binding affinity and site ID assignments made by ITC and X-ray crystallography. This quantitative mapping of ligand binding events at hotspot level resolution establishes the utility of the fragment-based competitive 19 F LB-NMR screening platform for hotspot-directed ligand profiling., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Active site lids are common features of enzymes and typically undergo conformational changes upon substrate binding to promote catalysis. Iodotyrosine deiodinase is no exception and contains a lid segment in all of its homologues from human to bacteria. The solution-state dynamics of the lid have now been characterized using 19 F NMR spectroscopy with a CF 3 -labeled enzyme and CF 3 O-labeled ligands. From two-dimensional 19 F- 19 F NMR exchange spectroscopy, interconversion rates between the free and bound states of a CF 3 O-substituted tyrosine (45 ± 10 s -1 ) and the protein label (40 ± 3 s -1 ) are very similar and suggest a correlation between ligand binding and conformational reorganization of the lid. Both occur at rates that are ∼100-fold faster than turnover, and therefore these steps do not limit catalysis. A simple CF 3 O-labeled phenol also binds to the active site and induces a conformational change in the lid segment that was not previously detectable by crystallography. Exchange rates of the ligand (130 ± 20 s -1 ) and protein (98 ± 8 s -1 ) in this example are faster than those above but remain self-consistent to affirm a correlation between ordering of the lid and binding of the ligand. Both ligands also protect the protein from limited proteolysis, as expected from their ability to stabilize a compact lid structure. However, the minimal turnover of simple phenol substrates indicates that such stabilization may be necessary but is not sufficient for efficient catalysis.

Structural characterization of protein-ligand binding interfaces at atomic resolution is essential for improving the design of specific and potent inhibitors. Herein, we explored fast 19 F- and 1 H-detected magic angle spinning NMR spectroscopy to investigate the interaction between two fluorinated ligand diastereomers with the microcrystalline galectin-3 carbohydrate recognition domain. The detailed environment around the fluorine atoms was mapped by 2D 13 C- 19 F and 1 H- 19 F dipolar correlation experiments and permitted characterization of the binding interface. Our results demonstrate that 19 F MAS NMR is a powerful tool for detailed characterization of protein-ligand interfaces and protein interactions at the atomic level.

Hydrofluoric Acid (HF) is considered one of the most hazardous chemicals used in industrial plants. Even small exposures to HF can have fatal consequences if not promptly and properly treated. Various research teams have presented numerous substances with the objective of capturing or detecting toxic HF gas. In this study, we explore the impact of HF gas on a single layer of SnS by employing density functional theory (DFT). The interaction nature between the gas molecule and the adsorbent is elucidated by analyzing the related adsorption energy, electronic structure properties and differential charge transfer. The findings indicate that HF is physically adsorbed on the pristine SnS with an adsorption energy value of -0.63 eV. By introducing a Sn mono vacancy defect, the modification of SnS enhances the adsorption energy to -1.26 eV, resulting in a chemisorption process. Molecular fluorine (F 2 ) was discovered to undergo a barrierless reaction with SnS, resulting in the formation of fluorine-substituted SnS. It has been discovered that the substitution of fluorine atoms enhances the reactivity of SnS towards hydro-gen fluoride gas. The adsorption potential of the studied structures towards HF gas was determined to be in the following order: F 2 SnS > V Sn -SnS > V S -SnS ∼ SnS. The current study is anticipated to offer new molecular insights that could lead to the creation of innovative devices for detecting or eliminating HF toxic gas from a specific atmosphere., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Fluorine ( 19 F) NMR is emerging as an invaluable analytical technique in chemistry, biochemistry, structural biology, material science, drug discovery, and medicine, especially due to the inherent rarity of naturally occurring fluorine in biological, organic, and inorganic compounds. Here, we revisit the under-reported problem of fluoride leaching from new and unused glass NMR tubes. We characterised the leaching of free fluoride from various types of new and unused glass NMR tubes over the course of several hours and quantify this contaminant to be at micromolar concentrations for typical NMR sample volumes across multiple glass types and brands. We find that this artefact is undetectable for samples prepared in quartz NMR tubes within the timeframes of our experiments. We also observed that pre-soaking new glass NMR tubes combined with rinsing removes this contamination below micromolar levels. Given the increasing popularity of 19 F NMR across a wide range of fields, increasing popularity of single-use screening tubes, the long collection times required for relaxation studies and samples of low concentrations, and the importance of avoiding contamination in all NMR experiments, we anticipate that our simple solution will be useful to biomolecular NMR spectroscopists., (© 2024. The Author(s).)

Membrane distillation (MD) equipped with omniphobic (non-wetting) membranes has found a niche in water reclamation from hypersaline industrial wastewater. Here, we examined the efficacy of non-fluorinated materials as surface coating agents for omniphobic MD membrane fabrication, and identified necessary mechanisms to attain a maximized wetting resistance using fluorine-free materials. We first prepared MD membranes with different surface chemistries using a series of linear alkylsilanes and polydimethylsiloxane (PDMS) as representative fluorine-free, low surface energy materials. Membranes modified with a longer chain alkylsilane exhibited a lower surface energy and demonstrated a greater wetting resistance in direct contact MD experiments using feedwaters of various surface tensions. Despite the nearly identical surface energy measured for the longest alkylsilane and PDMS, PDMS-modified membrane exhibited an extended antiwetting performance as compared to the membrane treated with the longest alkylsilane. To elucidate the source of the distinctive wetting resistance, we examined the nucleation and condensation kinetics on the surfaces with the different surface chemistries via environmental scanning electron microscopy. Our analysis suggests that the membranes treated with long chain alkylsilanes contain surface defects (i.e., hydrophilic regions) whereas the high mobility of the PDMS effectively minimizes the defect exposure, slowing down the condensation and subsequent surface wetting., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

In NMR spectroscopy of biomolecular systems, the use of fluorine-19 probes benefits from a clean background and high sensitivity. Therefore, 19 F-labeling procedures are of wide-spread interest. Here, we use 5-fluoroindole as a precursor for cost-effective residue-specific introduction of 5-fluorotryptophan (5F-Trp) into G protein-coupled receptors (GPCRs) expressed in Pichia pastoris. The method was successfully implemented with the neurokinin 1 receptor (NK1R). The 19 F-NMR spectra of 5F-Trp-labeled NK1R showed one well-separated high field-shifted resonance, which was assigned by mutational studies to the "toggle switch tryptophan". Residue-selective labeling thus enables site-specific investigations of this functionally important residue. The method described here is inexpensive, requires minimal genetic manipulation and can be expected to be applicable for yeast expression of GPCRs at large., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

• Anion photoelectron spectroscopy provides a direct measure of fluorinated isomers of phenolate. • The electron affinity of mono-fluorinated phenoxy radicals is found to depend on substitution site. • The increase in electron affinity is the sum of individual fluorinations, bar a small co-operative contribution. • Computational work recovers the observed trends. • A predictable electron affinity of fluorinated species offers design tools for application in fluorine chemistry. The site-specific fluorination of organic compounds can alter their electron affinity, EA , which in turn can be used to control their reactivity, physical properties, or binding affinities. Using anion photoelectron spectroscopy, we show that for the multiply fluorinated phenoxy radical, the change in EA is predominantly additive per fluorination and can be predicted by the simple formula: Δ EA = ∑ i Δ EA i − Δ EA C , where the numeric index i indicates the positions of fluorination. A small cooperative effect, Δ EA C , destabilizes the anion, but this only accounts for 11 % of the total Δ EA , in the extreme case of pentafluorophenolate. Our experimental results are consistent with those calculated using density functional theory, demonstrating the suitability of electronic structure calculations in the prediction of fluorination effects, for practical use in the synthetic design of organofluorines. [Display omitted] [ABSTRACT FROM AUTHOR]

Several novel copper (II) complexes of reduced Schiff bases containing fluoride substituents were prepared and structurally characterized by single-crystal X-ray diffraction. The complexes exhibited diverse structures, with the central atom in distorted tetrahedral geometry. The biological effects of the products were evaluated, specifically their cytotoxicity, antimicrobial, and antiurease activities, as well as affinity for albumin (BSA) and DNA (ct-DNA). The complexes showed marked cytotoxic activities in the HepG2 hepatocellular carcinoma cell line, considerably higher than the standard cisplatin. The cytotoxicity depended significantly on the substitution pattern. The best activity was observed in the complex with a trifluoromethyl group in position 4 of the benzene ring-the dichloro[(±)-trans- N , N '-bis-(4-trifluoromethylbenzyl)-cyclohexane-1,2-diamine]copper (II) complex, whose activity (IC 50 28.7 μM) was higher than that of the free ligand and markedly better than the activity of the standard cisplatin (IC 50 336.8 μM). The same complex also showed the highest antimicrobial effect in vitro. The affinity of the complexes towards bovine serum albumin (BSA) and calf thymus DNA (ct-DNA) was established as well, indicating only marginal differences between the complexes. In addition, all complexes were shown to be excellent inhibitors of the enzyme urease, with the IC 50 values in the lower micromolar region.

Oblique-incidence reflectivity difference (OIRD) is a dielectric constant-sensitive technique and exhibits intriguing applications in label-free and high-throughput detection of protein microarrays. With the outstanding advantage of being compatible with arbitrary substrates, however, the effect of the substrate, particularly its dielectric constant on the OIRD sensitivity has not been fully disclosed. In this paper, for the first time we investigated the dependence of OIRD sensitivity on the dielectric constant of the substrate under top-incident OIRD configuration by combining theoretical modeling and experimental evaluation. Optical modeling suggested that the higher dielectric constant substrate exhibits a higher intrinsic sensitivity. Experimentally, three substrates including glass, fluorine-doped tin oxide (FTO) and silicon (Si) with different dielectric constants were selected as microarray substrates and their detection performances were evaluated. In good agreement with the modeling, high dielectric constant Si-based microarray exhibited the highest sensitivity among three chips, reaching a detection limit of as low as 5 ng mL -1 with streptavidin as the model target. Quantification of captured targets on three chips with on-chip enzyme-linked immunosorbent assay (ELISA) further confirmed that the enhanced performance originates from the high dielectric constant enhanced intrinsic OIRD sensitivity. This work thus provides a new way to OIRD-based label-free microarrays with improved sensitivity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Weihua Hu reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The development and the use of fluorinated polyproline-type II (PPII) foldamers are still underexplored. Herein, trifluoromethyl pseudoprolines have been incorporated into polyproline backbones without affecting their PPII helicity. The ability of the trifluoromethyl groups to increase hydrophobicity and to act as 19 F NMR probes is demonstrated. Moreover, the enzymatic stability and the non-cytotoxicity of these fluorinated foldamers make them valuable templates for use in medicinal chemistry.

Increasing evidence has demonstrated that oxidative phosphorylation (OXPHOS) is closely associated with the progression of pancreatic cancer (PC). Given its central role in mitochondrial transcription, the human mitochondrial RNA polymerase (POLRMT) is a promising target for developing PC treatments. Herein, structure-activity relationship exploration led to the identification of compound S7 , which was the first reported POLRMT inhibitor possessing single-digit nanomolar potency of inhibiting PC cells proliferation. Mechanistic studies showed that compound S7 exerted antiproliferative effects without affecting the cell cycle, apoptosis, mitochondrial membrane potential (MMP), or intracellular reactive oxygen species (ROS) levels specifically in MIA PaCa-2 cells. Notably, compound S7 inhibited tumor growth in MIA PaCa-2 xenograft tumor model with a tumor growth inhibition (TGI) rate of 64.52% demonstrating significant improvement compared to the positive control (44.80%). In conclusion, this work enriched SARs of POLRMT inhibitors, and compound S7 deserved further investigations of drug-likeness as a candidate for PC treatment.

Fluorine (F) is a pivotal element in the formation of human dental and skeletal tissues, and the consumption of water and tea constitutes a significant source of fluoride intake. However, prolonged ingestion of water and tea with excessive fluoride content can lead to fluorosis, which poses a serious health hazard. In this manuscript, a novel turn-on fluorescent probe DCF synthesized by bis-coumarin and tert-butyldiphenylsilane (TBDPS) was introduced for detecting F - in potable water and tea infusions. By leveraging the unique chemical affinity between fluoride and silicon, F - triggers the silicon-oxygen bond cleavage in DCF, culminating in a conspicuous emission of yellow fluorescence. Validated through a succession of optical tests, this probe exhibits remarkable advantages in terms of superior selectivity, a low detection limit, a large Stokes shift, and robust interference resistance when detecting inorganic fluoride. Moreover, it can serve as portable test strips for on-site real-time identification and quantitative analysis of F - . Furthermore, the application of DCF for in-situ monitoring and imaging of F - in zebrafish and soybean root tissues proved its significant value for F - detection in both animal and plant systems. This probe potentially functions as an efficient instrument for delving into the toxic mechanisms of fluoride in physiological processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The structure of cis- or trans-bridged [GeF 5 ] - anionic chains have been investigated [Mallouk et al. (1984). Inorg. Chem. 23, 3160-3166] showing the first crystal structures of μ-F-bridged pentafluorogermanates. Herein, we report the second crystal structure of trans-pentafluorogermanate anions present in the crystal structure of sodium trans-pentafluorogermanate(IV) bis(hydrogen fluoride), Na[GeF 5 ]·2HF. The crystal structure [orthorhombic Pca2 1 , a = 12.3786 (3), b = 7.2189 (2), c = 11.4969 (3) Å and Z = 8] is built up from infinite chains of trans-linked [GeF 6 ] 2- octahedra, extending along the b axis and spanning a network of pentagonal bipyramidal distorted Na-centred polyhedra. These [NaF 7 ] polyhedra are linked in a trans-edge fashion via hydrogen fluoride molecules, in analogy to already known sodium hydrogen fluorides and potassium hydrogen fluorides., (open access.)

This research aimed to introduce a novel method for the valorization of mineral waste, focusing on the development of hydroxyapatite (HAP) as an effective and economical adsorbent for immobilizing fluoride ions (F - ) in soil. Hydroxyapatites were produced through the reaction between potassium dihydrogen phosphate (KH 2 PO 4 ) and calcium-abundant limestone soil (CLS). X-ray diffraction analyses revealed that the primary phases in HAP CLS were brushite (CaHPO 5 ·2H 2 O) and hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ). The FTIR spectra exhibited characteristics akin to natural HAP, including the presence of orthophosphate groups (PO 4 3- ), hydroxyl groups (OH - ), and both A/B types of carbonates in the apatite structure. The morphology of the synthesized HAP, as observed through SEM-EDS, was consistent with that of phosphocalcic hydroxyapatite crystals. The EDS results indicated a Ca/P atomic ratio of 1.7 for HAP CLS , aligning closely with the typical hydroxyapatite stoichiometry (Ca/P = 1.67). The application of HAP to reduce fluoride (F - ) levels in soil proved to be successful; introducing 1% of various HAP formulations reduced the fluoride concentration from 51.4 mg/kg in untreated soil to levels below the IWSI limit (10 mg/kg), achieving a reduction to 8.1 mg/kg for HAP CLS . The sequential extraction of fluoride demonstrated that after soil treatment, fluoride was predominantly removed from the residual fraction (Fraction 4) and was effectively sequestered by the hydroxyapatites (Ca 10 (PO 4 ) 6 (OH) 2 ) through anionic exchange with hydroxide ions (OH - ), resulting in the formation of stable and insoluble fluorapatite (Ca 10 (PO 4 ) 6 F 2 )., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The incorporation of fluorine atoms into a biomacromolecule provides a background-free and environmentally sensitive reporter of structure, conformation and interactions using 19 F NMR. There are several methods to introduce the 19 F reporter - either by synthetic incorporation via solid phase peptide synthesis; by suppressing the incorporation or biosynthesis of a natural amino acid and supplementing the growth media with a fluorinated counterpart during protein expression; and by genetic code expansion to add new amino acids to the amino acid alphabet. This review aims to discuss progress in the field of introducing fluorinated handles into biomolecules for NMR studies by post-translational bioconjugation or 'fluorine-tagging'. We will discuss the range of chemical tagging 'warheads' that have been used, explore the applications of fluorine tags, discuss ways to enhance reporter sensitivity and how the signal to noise ratios can be boosted. Finally, we consider some key challenges of the field and offer some ideas for future directions., (© 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Polyene cyclizations are among the most complex and challenging transformations in biology. In a single reaction step, multiple carbon-carbon bonds, ring systems and stereogenic centres are constituted from simple, acyclic precursors 1-3 . Simultaneously achieving this kind of precise control over product distribution and stereochemistry poses a formidable task for chemists. In particular, the polyene cyclization of (3E,7E)-homofarnesol to the valuable naturally occurring ambergris odorant (-)-ambrox is recognized as a longstanding challenge in chemical synthesis 1,4-7 . Here we report a diastereoselective and enantioselective synthesis of (-)-ambrox and the sesquiterpene lactone natural product (+)-sclareolide by a catalytic asymmetric polyene cyclization by using a highly Brønsted-acidic and confined imidodiphosphorimidate catalyst in the presence of fluorinated alcohols. Several experiments, including deuterium-labelling studies, suggest that the reaction predominantly proceeds through a concerted pathway in line with the Stork-Eschenmoser hypothesis 8-10 . Mechanistic studies show the importance of the enzyme-like microenvironment of the imidodiphosphorimidate catalyst for attaining exceptionally high selectivities, previously thought to be achievable only in enzyme-catalysed polyene cyclizations., (© 2024. The Author(s).)

Thermal inactivation is a major bottleneck to the scalable production, storage, and transportation of protein-based reagents and therapies. Failures in temperature control both compromise protein bioactivity and increase the risk of microorganismal contamination. Herein, we report the rational design of fluorochemical additives that promiscuously bind to and coat the surfaces of proteins to enable their stable dispersion within fluorous solvents. By replacing traditional aqueous liquids with fluorinated media, this strategy conformationally rigidifies proteins to preserve their structure and function at extreme temperatures (≥90 °C). We show that fluorous protein formulations resist contamination by bacterial, fungal, and viral pathogens, which require aqueous environments for survival, and display equivalent serum bioavailability to standard saline samples in animal models. Importantly, by designing dispersants that decouple from the protein surface in physiologic solutions, we deliver a fluorochemical formulation that does not alter the pharmacologic function or safety profile of the functionalized protein in vivo . As a result, this nonaqueous protein storage paradigm is poised to open technological opportunities in the design of shelf-stable protein reagents and biopharmaceuticals.

The purpose of this Special Issue is to showcase the latest findings in fluorine chemistry [...].

The unique properties of per- and polyfluoroalkyl substances (PFAS) have led to their extensive use in consumer products, including ski wax. Based on the risks associated with PFAS, and to align with PFAS regulations, the international ski federation (FIS) implemented a ban on products containing "C 8 fluorocarbons/perfluorooctanoate (PFOA)" at all FIS events from the 2021/2022 season, leading manufactures to shift their formulations towards short-chain PFAS chemistries. To date, most studies characterising PFAS in ski waxes have measured a suite of individual substances using targeted analytical approaches. However, the fraction of total fluorine (TF) in the wax accounted for by these substances remains unclear. In this study, we sought to address this question by applying a multi-platform, fluorine mass balance approach to a total of 10 commercially available ski wax products. Analysis of TF by combustion ion chromatography (CIC) revealed concentrations of 1040-51700 μg F g -1 for the different fluorinated waxes. In comparison, extractable organic fluorine (EOF) determined in methanol extracts by CIC (and later confirmed by inductively-coupled plasma-mass spectrometry and 19 F- nuclear magnetic resonance spectroscopy) ranged from 92 to 3160 μg g -1 , accounting for only 3-8.8 % of total fluorine (TF). Further characterisation of extracts by cyclic ion mobility-mass spectrometry (IMS) revealed 15 individual PFAS with perfluoroalkyl carboxylic acid concentrations up to 33 μg F g -1 , and 3 products exceeding the regulatory limit for PFOA (0.025 μg g -1 ) by a factor of up to 100. The sum of all PFAS accounted for only 0.01-1.0 % of EOF, implying a high percentage of unidentified PFAS, thus, pyrolysis gas chromatography-mass spectrometry was used to provide evidence of the nature of the non-extractable fluorine present in the ski wax products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)