Self-assembling dendrimer nanosystems for specific fluorine magnetic resonance imaging and effective theranostic treatment of tumors.

Fluorine magnetic resonance imaging (19F-MRI) is particularly promising for biomedical applications owing to the absence of fluorine in most biological systems. However, its use has been limited by the lack of safe and water-soluble imaging agents with high fluorine contents and suitable relaxation properties. We report innovative 19F-MRI agents based on supramolecular dendrimers self-assembled by an amphiphilic dendrimer composed of a hydrophobic alkyl chain and a hydrophilic dendron. Specifically, this amphiphilic dendrimer bears multiple negatively charged terminals with high fluorine content, which effectively prevented intra- and intermolecular aggregation of fluorinated entities via electrostatic repulsion. This permitted high fluorine nuclei mobility alongside good water solubility with favorable relaxation properties for use in 19F-MRI. Importantly, the self-assembling 19F-MRI agent was able to encapsulate the near-infrared fluorescence (NIRF) agent DiR and the anticancer drug paclitaxel for multimodal 19F-MRI and NIRF imaging of and theranostics for pancreatic cancer, a deadly disease for which there remains no adequate early detection method or efficacious treatment. The 19F-MRI and multimodal 19F-MRI and NIRF imaging studies on human pancreatic cancer xenografts in mice confirmed the capability of both imaging modalities to specifically image the tumors and demonstrated the efficacy of the theranostic agent in cancer treatment, largely outperforming the clinical anticancer drug paclitaxel. Consequently, these dendrimer nanosystems constitute promising 19F-MRI agents for effective cancer management. This study offers a broad avenue to the construction of 19F-MRI agents and theranostics, exploiting self-assembling supramolecular dendrimer chemistry.

Fluorinated Protein-Ligand Complexes: A Computational Perspective.

Fluorine is an element renowned for its unique properties. Its powerful capability to modulate molecular properties makes it an attractive substituent for protein binding ligands; however, the rational design of fluorination can be challenging with effects on interactions and binding energies being difficult to predict. In this Perspective, we highlight how computational methods help us to understand the role of fluorine in protein-ligand binding with a focus on molecular simulation. We underline the importance of an accurate force field, present fluoride channels as a showcase for biomolecular interactions with fluorine, and discuss fluorine specific interactions like the ability to form hydrogen bonds and interactions with aryl groups. We put special emphasis on the disruption of water networks and entropic effects.

Modification and characterization of a novel and fluorine-free cellulose nanofiber with hydrophobic and oleophobic properties.

In this study, a brand-new, easy, and environmentally friendly approach for chemically functionalizing 2,2,6,6-tetramethylpiperidinyloxyl radical (TEMPO)-oxidized cellulose nanofiber (TOCNF) to produce modified cellulose nanofiber (octadecylamine-citric acid-CNF) was proposed. Effects of octadecylamine (ODA)/TOCNF mass ratio on the chemical structure, morphology, surface hydrophobicity and oleophobicity were studied. According to Fourier transform infrared spectroscopy (FTIR) analysis, ODA was successfully grafted onto the TOCNF by simple citric acid (CA) esterification and amidation reactions. Scanning electron microscopy (SEM) showed that a new rough structure was formed on the ODA-CA-CNF surface. The water contact angle (WCA) and the castor oil contact angle (OCA) of the ODA-CA-CNF reached 139.6° and 130.6°, respectively. The high-grafting-amount ODA-CA-CNF was sprayed onto paper, and the OCA reached 118.4°, which indicated good oil-resistance performance. The low-grafting-amount ODA-CNF was applied in a pH-responsive indicator film, exhibiting a colour change in response to the pH level, which can be applied in smart food packaging. The ODA-CA-CNF with excellent water/oil-resistance properties and fluorine-free properties can replace petrochemical materials and can be used in the fields of fluorine-free oil-proof paper.

A multi-platform approach for the comprehensive analysis of per- and polyfluoroalkyl substances (PFAS) and fluorine mass balance in commercial ski wax products.

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 "C8 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 19F- 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.

Synergistic effects of Co-pyrolysis on the immobilization and transformation of lead (Pb), chromium (Cr), nickel (Ni), and fluorine (F) in phosphogypsum-biomass mixtures.

Co-pyrolysis of biomass with phosphogypsum (PG) presents an effective strategy for facilitating the recycling of PG resources. However, it is crucial to note the environmental threats arising from the presence of Pb, Cr, Ni, and F in PG. This study investigated the effect of immobilization and transformation of four elements during co-pyrolysis with biomass and its components. The co-pyrolysis experiments were carried out in a tube furnace with a mixture of PG and corn stover (CS), cellulose (C), lignin (L), glucose (G). Co-pyrolysis occurred at varying temperatures (600 °C, 700 °C, 800 °C, and 900 °C) and different addition ratios (10%, 15%, and 20%). The results indicated that an increase in co-pyrolysis temperature was more conducive to the immobilization and transformation of harmful elements in PG, demonstrating significant efficacy in controlling F. Additionally, the addition of biomass components exerts a significant impact on inhibiting product toxicity, with small molecules such as glucose playing a prominent role in this process. The mechanism underlying the control of harmful elements during co-pyrolysis of PG and biomass was characterized by three main aspects. Firstly, biomass components have the potential to melt-encapsulate the harmful elements in PG, leading to precipitation. Secondly, the pyrolysis gas produced during the co-pyrolysis process contributes to the formation of a rich pore structure in the product. Finally, this process aids in transforming hazardous substances into less harmful forms and stabilizing these elements. The findings of this study are instrumental in optimizing the biomass and PG blend to mitigate the environmental impact of their co-pyrolysis products.

Quantifying CO-release from a photo-CORM using 19F NMR: An investigation into light-induced CO delivery.

Carbon monoxide (CO) is an innate signaling molecule that can regulate immune responses and interact with crucial elements of the circadian clock. Moreover, pharmacologically, CO has been substantiated for its therapeutic advantages in animal models of diverse pathological conditions. Given that an excessive level of CO can be toxic, it is imperative to quantify the necessary amount for therapeutic use accurately. However, estimating gaseous CO is notably challenging. Therefore, novel techniques are essential to quantify CO in therapeutic applications and overcome this obstacle precisely. The classical Myoglobin (Mb) assay technique has been extensively used to determine the amount of CO-release from CO-releasing molecules (CORMs) within therapeutic contexts. Nevertheless, specific challenges arise when applying the Mb assay to evaluate CORMs featuring innovative molecular architectures. Here, we report a fluorinated photo-CORM (CORM-FBS) for the photo-induced CO-release. We employed the 19F NMR spectroscopy approach to monitor the release of CO as well as quantitative evaluation of CO release. This new 19F NMR approach opens immense opportunities for researchers to develop reliable techniques for identifying molecular structures, quantitative studies of drug metabolism, and monitoring the reaction process.

A Dopamine Detection Sensor Based on Au-Decorated NiS2 and Its Medical Application.

This article reports a simple hydrothermal method for synthesizing nickel disulfide (NiS2) on the surface of fluorine-doped tin oxide (FTO) glass, followed by the deposition of 5 nm Au nanoparticles on the electrode surface by physical vapor deposition. This process ensures the uniform distribution of Au nanoparticles on the NiS2 surface to enhance its conductivity. Finally, an Au@NiS2-FTO electrochemical biosensor is obtained for the detection of dopamine (DA). The composite material is characterized using transmission electron microscopy (TEM), UV-Vis spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The electrochemical properties of the sensor are investigated using cyclic voltammetry (CV), differential pulse voltammetry (DPV), and time current curves in a 0.1 M PBS solution (pH = 7.3). In the detection of DA, Au@NiS2-FTO exhibits a wide linear detection range (0.1~1000 µM), low detection limit (1 nM), and fast response time (0.1 s). After the addition of interfering substances, such as glucose, L-ascorbic acid, uric acid, CaCl2, NaCl, and KCl, the electrode potential remains relatively unchanged, demonstrating its strong anti-interference capability. It also demonstrates strong sensitivity and reproducibility. The obtained Au@NiS2-FTO provides a simple and easy-to-operate example for constructing nanometer catalysts with enzyme-like properties. These results provide a promising method utilizing Au coating to enhance the conductivity of transition metal sulfides.

Fluorinated 1,7-DO2A-Based Iron(II) Complexes as Sensitive 19F MRI Molecular Probes for Visualizing Renal Dysfunction in Living Mice.

Kidney diseases have become an important global health concern due to their high incidence, inefficient diagnosis, and poor prognosis. Devising direct methods, especially imaging means, to assess renal function is the key for better understanding the mechanisms of various kidney diseases and subsequent development of effective treatment. Herein, we developed a fluorinated ferrous chelate-based sensitive probe, 1,7-DO2A-Fe(II)-F18 (Probe 1), for 19F magnetic resonance imaging (MRI). This highly fluorinated probe (containing 18 chemically equivalent 19F atoms with a fluorine content at 35 wt %) achieves a 15-time enhancement in signal intensity compared with the fluorine-containing ligand alone due to the appropriately regulated 19F relaxation times by the ferrous ion, which significantly increases imaging sensitivity and reduces acquisition time. Owing to its high aqueous solubility, biostability, and biocompatibility, this probe could be rapidly cleared by kidneys, which provides a means for monitoring renal dysfunction via 19F MRI. With this probe, we accomplish in vivo imaging of the impaired renal dysfunction caused by various kidney diseases including acute kidney injury, unilateral ureteral obstruction, and renal fibrosis at different stages. Our study illustrates the promising potential of Probe 1 for in vivo real-time visualization of kidney dysfunction, which is beneficial for the study, diagnosis, and even stratification of different kidney diseases. Furthermore, the design strategy of our probe is inspiring for the development of more high-performance 19F MRI probes for monitoring various biological processes.

Probing and evaluating transmembrane chloride ion transport in double walled trifluorophenyl/phthalimide extended calix[4]pyrrole-based supramolecular receptors.

Therapeutic applications have sparked increased interest in the use of synthetic anion receptors for ion transport across lipid membranes. In this context, the construction of synthetic transmembrane transporters for the physiologically important chloride ion is currently of enormous interest. As a result, considerable effort is being devoted to the design and synthesis of artificial transmembrane chloride ion transporters. However, only inadequate progress has been made in developing macrocyclic chloride ion transporters using the fundamental principles of supramolecular chemistry, and hence this field entails fostering investigations. In this investigation, the synthesis of two new double walled trifluorophenyl/phthalimide extended calix[4]pyrrole (C4P) receptors (3 and 7) has been successfully reported. 1H-NMR titration and HRMS studies confirmed the 1 : 1 binding stoichiometry of the chloride ion with these receptors in the solution phase (only receptor 3b was studied by 1H-NMR). Regarding ion transport of 3b and 7, when studied in the HPTS-based vesicular system, 3b showed better activity with an EC50 value of 0.39 µM. The detailed ion transport studies on 3b have revealed that ion transport occurs through the Cl-/NO3- antiport mode.

Exploring fluorine-substituted piperidines as potential therapeutics for diabetes mellitus and Alzheimer's diseases.

In the current study, a series of fluorine-substituted piperidine derivatives (1-8) has been synthesized and characterized by various spectroscopic techniques. In vitro and in vivo enzyme inhibitory studies were conducted to elucidate the efficacy of these compounds, shedding light on their potential therapeutic applications. To the best of our knowledge, for the first time, these heterocyclic structures have been investigated against α-glucosidase and cholinesterase enzymes. The antioxidant activity of the synthesized compounds was also assessed. Evaluation of synthesized compounds revealed notable inhibitory effects on α-glucosidase and cholinesterases. Remarkably, the target compounds (1-8) exhibited extraordinary α-glucosidase inhibitory activity as compared to the standard acarbose by several-fold. Subsequently, the potential antidiabetic effects of compounds 2, 4, 5, and 6 were validated using a STZ-induced diabetic rat model. Kinetic studies were also performed to understand the mechanism of inhibition, while structure-activity relationship analyses provided valuable insights into the structural features governing enzyme inhibition. Kinetic investigations revealed that compound 4 displayed a competitive mode of inhibition against α-glucosidase, whereas compound 2 demonstrated mixed-type behavior against AChE. To delve deeper into the binding interactions between the synthesized compounds and their respective enzyme targets, molecular docking studies were conducted. Overall, our findings highlight the promising potential of these densely substituted piperidines as multifunctional agents for the treatment of diseases associated with dysregulated glucose metabolism and cholinergic dysfunction.

Label-free OIRD detection of protein microarrays on high dielectric constant substrate with enhanced intrinsic sensitivity.

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.

Gold nanoparticle-decorated fluorine-doped tin oxide substrate for sensitive label-free OIRD microarray chips.

Oblique incidence reflectance difference (OIRD) is an emerging technique enabling real-time and label-free detection of bio-affinity binding events on microarrays. The interfacial architecture of the microarray chip is critical to the performance of OIRD detection. In this work, a sensitive label-free OIRD microarray chip was developed by using gold nanoparticle-decorated fluorine-doped tin oxide (AuNPs-FTO) slides as a chip substrate. This AuNPs-FTO chip demonstrates a higher signal-to-noise ratio and improved sensitivity compared to that built on FTO glass, showing a detection limit of as low as 10 ng mL-1 for the model target, HRP-conjugated streptavidin. On-chip ELISA experiments and optical calculations suggest that the enhanced performance is not only due to the higher probe density enabling a high capture efficiency toward the target, but most importantly, the AuNP layer arouses optical interference to improve the intrinsic sensitivity of OIRD. This work provides an effective strategy for constructing OIRD-based microarray chips with enhanced sensitivity, and may help extend their practical applications in various fields.

(2S,4S)-5-Fluoroleucine, (2S,4R)-5-Fluoroleucine, and 5,5'-Difluoroleucine in Escherichia coli PpiB: Protein Production, 19F NMR, and Ligand Sensing Enhanced by the γ-Gauche Effect.

Global substitution of leucine for analogues containing CH2F instead of methyl groups delivers proteins with multiple sites for monitoring by 19F nuclear magnetic resonance (NMR) spectroscopy. The 19 kDa Escherichia coli peptidyl-prolyl cis-trans isomerase B (PpiB) was prepared with uniform high-level substitution of leucine by (2S,4S)-5-fluoroleucine, (2S,4R)-5-fluoroleucine, or 5,5'-difluoroleucine. The stability of the samples toward thermal denaturation was little altered compared to the wild-type protein. 19F nuclear magnetic resonance (NMR) spectra showed large chemical shift dispersions between 6 and 17 ppm. The 19F chemical shifts correlate with the three-bond 1H-19F couplings (3JHF), providing the first experimental verification of the γ-gauche effect predicted by [Feeney, J. J. Am. Chem. Soc. 1996, 118, 8700-8706] and establishing the effect as the predominant determinant of the 19F chemical shifts of CH2F groups. Individual CH2F groups can be confined to single rotameric states by the protein environment, but most CH2F groups exchange between different rotamers at a rate that is fast on the NMR chemical shift scale. Interactions between fluorine atoms in 5,5'-difluoroleucine bias the CH2F rotamers in agreement with results obtained previously for 1,3-difluoropropane. The sensitivity of the 19F chemical shift to the rotameric state of the CH2F groups potentially renders them particularly sensitive for detecting allosteric effects.

Effects of swine manure and straw biochars on fluorine adsorption-desorption in soils.

With increasing global awareness of soil health, attention must be paid to fluorine exposure in soils, which poses a threat to human health. Therefore, this study aimed to study the fluorine adsorption characteristics of swine manure and straw biochars and their impact on fluorine adsorption-desorption in soil with batch experiments. The biochar samples originated from high-temperature anaerobic cracking of swine manure (350°C, 500°C, and 650°C) and straw (500°C). Results indicated that the adsorption of soil fluorine reached adsorption equilibrium at around 4 h after the mixing of swine manure and straw biochar. Fluorine adsorption kinetics using these biochars conformed to the quasi-two-stage kinetic model. The fluorine adsorption kinetics for biochar-treated soils conformed to the double-constant equation and the Elovich equation, and the soil treated with straw biochar showed the fastest fluorine adsorption rate. The adsorption isotherms of fluorine for biochars and biochar-treated soils could be fitted by the isothermal adsorption model of Langmuir and Freundlich. The maximal equilibrium quantity of fluorine was 73.66 mg/g for swine manure biochar. The soil, adding with 2% of swine manure biochar achieved with showed at 650°C had the smallest adsorption. This study also shows that the adsorption of fluorine by biochar gradually decreased with the increase of pH. Comparing with other factors, the mixture pH with biochars added had a significant effect on fluorine adsorption. The decreased fluorine adsorption capacities for soils treated with swine manure and straw biochars were closely related to the increased pH in soils after adding biochars. Considering the fluorine threat in soil, this study provides a theoretical basis for the application of biochars on soil fluorine adsorption.

Synthesis of Fluorinated Nucleosides/Nucleotides and Their Antiviral Properties.

The FDA has approved several drugs based on the fluorinated nucleoside pharmacophore, and numerous drugs are currently in clinical trials. Fluorine-containing nucleos(t)ides offer significant antiviral and anticancer activity. The insertion of a fluorine atom, either in the base or sugar of nucleos(t)ides, alters its electronic and steric parameters and transforms the lipophilicity, pharmacodynamic, and pharmacokinetic properties of these moieties. The fluorine atom restricts the oxidative metabolism of drugs and provides enzymatic metabolic stability towards the glycosidic bond of the nucleos(t)ide. The incorporation of fluorine also demonstrates additional hydrogen bonding interactions in receptors with enhanced biological profiles. The present article discusses the synthetic methodology and antiviral activities of FDA-approved drugs and ongoing fluoro-containing nucleos(t)ide drug candidates in clinical trials.

Optoelectronic Response to the Fluor Ion Bond on 4-(4,4,5,5-Tetramethyl-1,3,2-dioxoborolan-2-yl)benzaldehyde.

Boronate esters are a class of compounds containing a boron atom bonded to two oxygen atoms in an ester group, often being used as precursors in the synthesis of other materials. The characterization of the structure and properties of esters is usually carried out by UV-visible, infrared, and nuclear magnetic resonance (NMR) spectroscopic techniques. With the aim to better understand our experimental data, in this article, the density functional theory (DFT) is used to analyze the UV-visible and infrared spectra, as well as the isotropic shielding and chemical shifts of the hydrogen atoms 1H, carbon 13C and boron 11B in the compound 4-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)benzaldehyde. Furthermore, this study considers the change in its electronic and spectroscopic properties of this particular ester, when its boron atom is coordinated with a fluoride anion. The calculations were carried out using the LSDA and B3LYP functionals in Gaussian-16, and PBE in CASTEP. The results show that the B3LYP functional gives the best approximation to the experimental data. The formation of a coordinated covalent B-F bond highlights the remarkable sensitivity of the NMR chemical shifts of carbon, oxygen, and boron atoms and their surroundings. Furthermore, this bond also highlights the changes in the electron transitions bands n → π* and π → π* during the absorption and emission of a photon in the UV-vis, and in the stretching bands of the C=C bonds, and bending of BO2 in the infrared spectrum. This study not only contributes to the understanding of the properties of boronate esters but also provides important information on the interactions and responses optoelectronic of the compound when is bonded to a fluorine atom.

Development of Ln(III) Derivatives as 19F Parashift Probes.

19F parashift probes with paramagnetically shifted reporter nuclei provide attractive platforms to develop molecular imaging probes. These probes enable ratiometric detection of molecular disease markers using a direct detection technique. Here, we describe a series of trivalent lanthanide (Ln(III)) complexes that are structural analogues of the clinically approved MR contrast agent (CA) ProHance to obtain LnL 19F parashift probes. We evaluated trans-gadolinium paramagnetic lanthanides compared to diamagnetic YL for 19F chemical shift and relaxation rate enhancement. The paramagnetic contribution to chemical shift (δPCS) for paramagnetic LnL exhibited either shifts to lower frequency (δPCS < 0 for TbL, DyL, and HoL) or shifts to higher frequency (δPCS > 0 for ErL, TmL, and YbL) compared to YL 19F spectroscopic signal. Zero-echo time pulse sequences achieved 56-fold sensitivity enhancement for DyL over YL, while developing probe-specific pulse sequences with fast delay times and acquisition times achieved 0.6-fold enhancement in limit of detection for DyL. DyL provides an attractive platform to develop 19F parashift probes for ratiometric detection of enzymatic activity.

A V-shaped bis-coumarin based fluorescence probe for F- detection in tea infusions and potable water and bioimaging applications in living systems.

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.

Total and Class-Specific Determination of Fluorinated Compounds in Consumer and Food Packaging Samples Using Fluorine-19 Solid-State Nuclear Magnetic Resonance Spectroscopy.

Hamburger wrapping paper, coated with water-based barrier coatings, used in the food packaging industry was studied by using the total organic fluorine (TOF) method based on combustion ion chromatography and fluorine-19 solid-state nuclear magnetic resonance (19F ss-NMR) spectroscopy. Although the TOF method is a fast and affordable method used to screen for per- and polyfluoroalkyl substances (PFAS), the amount of fluorine it measures is heavily dependent on the extraction step and, therefore could lead to inaccurate results. Fluorine-19 ss-NMR spectroscopy can differentiate between organic and inorganic fluorinated sources, eliminating the need for sample clean up. To illustrate this, the 19F ss-NMR spectra of clean coated paper samples that contained naturally occurring F- ions from the talc raw material and spiked samples containing perfluorooctanoic acid were compared. A range of experimental conditions was explored to improve sensitivity for low PFAS concentrations (in the order of 10-20 mg/kg). Despite the disadvantages of ss-NMR spectroscopy, such as the low limit of detection and resolution, the results demonstrate it can be a viable tool to directly detect PFAS moieties in consumer and food packaging. Therefore, 19F solid-state NMR spectroscopy challenges and complements current methods, which only provide indirect evidence of the presence of PFAS.

Fluorine-modified polymers reduce the adsorption of immune-reactive proteins to PEGylated gold nanoparticles.

Aim: To investigate the influence of fluorine in reducing the adsorption of immune-reactive proteins onto PEGylated gold nanoparticles. Methods: Reversible addition fragmentation chain transfer polymerization, the Turkevich method and ligand exchange were used to prepare polymer-coated gold nanoparticles. Subsequent in vitro physicochemical and biological characterizations and proteomic analysis were performed. Results: Fluorine-modified polymers reduced the adsorption of complement and other immune-reactive proteins while potentially improving circulatory times and modulating liver toxicity by reducing apolipoprotein E adsorption. Fluorine actively discouraged phagocytosis while encouraging the adsorption of therapeutic targets, CD209 and signaling molecule calreticulin. Conclusion: This study suggests that the addition of fluorine in the surface coating of nanoparticles could lead to improved performance in nanomedicine designed for the intravenous delivery of cargos.

Nanomedicines are based around the delivery of therapies by tiny, nanosized delivery vehicles. This method offers a much better way of specifically targeting life-threatening diseases. For fast delivery, nanomedicines can be injected into the blood (intravenously); however, this often leads to an unwanted and exaggerated immune response. The immune system is activated by proteins in the blood that attach themselves to nanoparticles through various chemical interactions (the protein corona effect). Fluorine is a chemical routinely used in surfactants such as firefighting foam and more recently in molecular imaging and nanoparticles designed for the delivery of therapies aimed at cancer. While fluorine has great potential to improve the cellular uptake of therapies, little is known about whether it can also help camouflage the nanoparticles against the immune system responses. Here, using fluorinated polymer-coated gold nanoparticles, the authors demonstrate that fluorine reduces uptake by immune cells and is highly effective at reducing the binding of immune system-initiating proteins. This work successfully illustrates the rationale for more widespread investigation of fluorine during the development of polymer-coated nanoparticles designed for the intravenous delivery of nanomedicines.