Expedient Access to 18F-Fluoroheteroarenes via Deaminative Radiofluorination of Aniline-Derived Pyridinium Salts.

Herein, we disclose that pyridinium salts derived from abundant (hetero)anilines represent a novel precursor class for nucleophilic aromatic substitution reactions with [18F]fluoride. The value of this new 18F-fluorodeamination is demonstrated with the synthesis of over 30 structurally diverse and complex heteroaryl 18F-fluorides, several derived from scaffolds that were yet to be labelled with fluorine-18. The protocol tolerates heteroarenes and functionalities commonly found in drug discovery libraries, and is amenable to scale-up and automation on a commercial radiosynthesiser.

Sociodemographic factors and Child Opportunity Index disparities associated with missed care opportunities in pediatric patients with lymphoma and leukemia referred for FDG-PET/CT.

BACKGROUND: Little data exists on the association of missed care opportunities (MCOs) in children referred for nuclear medicine/nuclear oncology imaging examinations and socioeconomic disparities. OBJECTIVE: To determine the prevalence of MCOs in children with lymphoma/leukemia scheduled for fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and the impact of sociodemographic factors and Child Opportunity Index (COI). MATERIALS AND METHODS: Retrospective analysis of MCOs in children with lymphoma/leukemia scheduled for FDG-PET/CT (2012 to 2022) was performed. In univariate analysis, patient, neighborhood, and appointment data were assessed across MCOs and completed appointments. Logistic regression evaluated independent effects of patient-, neighborhood-, and appointment-level factors with MCOs. Two-sided P-value < .05 was considered statistically significant. RESULTS: In 643 FDG-PET/CT appointments (n = 293 patients; median age 15 years (IQR 11.0-17.0 years); 37.9% female), there were 20 MCOs (3.1%) involving 16 patients. Only 8.2% appointments involved Black/African American non-Hispanic/Latino patients, yet they made up a quarter of total MCOs. Patients living in neighborhoods with very low or low COI experienced significantly higher MCOs versus zip codes with very high COI (6.9% vs. 0.8%; P = 0.02). Logistic regression revealed significantly increased likelihood of MCOs for patients aged 18 to 21 [odds ratio (OR) 4.50; 95% CI 1.53-13.27; P = 0.007], Black/African American non-Hispanic/Latino (OR 3.20; 95% CI 1.08-9.49; P = 0.04), zip codes with very low or low COI (OR 9.60; 95% CI 1.24-74.30; P = 0.03), and unknown insurance status. CONCLUSION: Children with lymphoma/leukemia, living in zip codes with very low or low COI, and who identified as Black/African American non-Hispanic/Latino experienced more MCOs. Our study supports the need to address intersecting sociodemographic, neighborhood, and health system factors that will improve equitable access to necessary healthcare imaging for children.

Fluorine Modification Promoted Water Dissociation into Atomic Hydrogen on a Copper Electrode for Efficient Neutral Nitrate Reduction and Ammonia Recovery.

Electrocatalytic nitrate reduction to ammonia (NITRR) offers an attractive solution for alleviating environmental concerns, yet in neutral media, it is challenging as a result of the reliance on the atomic hydrogen (H*) supply by breaking the stubborn HO-H bond (∼492 kJ/mol) of H2O. Herein, we demonstrate that fluorine modification on a Cu electrode (F-NFs/CF) favors the formation of an O-H···F hydrogen bond at the Cu-H2O interface, remarkably stretching the O-H bond of H2O from 0.98 to 1.01 Å and lowering the energy barrier of water dissociation into H* from 0.64 to 0.35 eV at neutral pH. As a benefit from these advantages, F-NFs/CF could rapidly reduce NO3- to NH3 with a rate constant of 0.055 min-1 and a NH3 selectivity of ∼100%, far higher than those (0.004 min-1 and 9.2%) of the Cu counterpart. More importantly, we constructed a flow-through coupled device consisting of a NITRR electrolyzer and a NH3 recovery unit, realizing 98.1% of total nitrogen removal with 99.3% of NH3 recovery and reducing the denitrification cost to $5.1/kg of N. This study offers an effective strategy to manipulate the generation of H* from water dissociation for efficient NO3--to-NH3 conversion and sheds light on the importance of surface modification on a Cu electrode toward electrochemical reactions.

8-Bicycloalkyl-CPFPX derivatives as potent and selective tools for in vivo imaging of the A1 adenosine receptor.

Imaging of the A1 adenosine receptor (A1R) by positron emission tomography (PET) with 8-cyclopentyl-3-(3-[18F]fluoropropyl)-1-propyl-xanthine ([18F]CPFPX) has been widely used in preclinical and clinical studies. However, this radioligand suffers from rapid peripheral metabolism and subsequent accumulation of radiometabolites in the vascular compartment. In the present work, we prepared four derivatives of CPFPX by replacement of the cyclopentyl group with norbornane moieties. These derivatives were evaluated by competition binding studies, microsomal stability assays and LC-MS analysis of microsomal metabolites. In addition, the 18F-labeled isotopologue of 8-(1-norbornyl)-3-(3-fluoropropyl)-1-propylxanthine (1-NBX) as the most promising candidate was prepared by radiofluorination of the corresponding tosylate precursor and the resulting radioligand ([18F]1-NBX) was evaluated by permeability assays with Caco-2 cells and in vitro autoradiography in rat brain slices. Our results demonstrate that 1-NBX exhibits significantly improved A1R affinity and selectivity when compared to CPFPX and that it does not give rise to lipophilic metabolites expected to cross the blood-brain-barrier in microsomal assays. Furthermore, [18F]1-NBX showed a high passive permeability (Pc = 6.9 ± 2.9 × 10-5 cm/s) and in vitro autoradiography with this radioligand resulted in a distribution pattern matching A1R expression in the brain. Moreover, a low degree of non-specific binding (5%) was observed. Taken together, these findings identify [18F]1-NBX as a promising candidate for further preclinical evaluation as potential PET tracer for A1R imaging.

Fluorine-functionalized magnetic amino microporous organic network for enrichment of perfluoroalkyl substances.

Perfluoroalkyl substances (PFAS) are persistent organic pollutants that pose significant risks to human health and the environment. Efficient and selective enrichment of these compounds was crucial for their accurate detection and quantification in complex matrices. Herein, we report a novel magnetic solid-phase extraction (MSPE) method using fluorine-functionalized magnetic amino-microporous organic network (Fe3O4@MONNH2@F7) adsorbent for the efficient enrichment of PFAS from aqueous samples. The core-shell Fe3O4@MONNH2@F7 nanosphere was synthesized, featuring magnetic Fe3O4 nanoparticles as the core and a porous amino-functionalized MONs coating as the shell, which was further modified by fluorination. The synthesized adsorbent material exhibited high specific surface area, hydrophobicity, and abundant fluorine groups, facilitating efficient and selective adsorption of PFAS via electrostatic attraction, hydrophobic-hydrophobic interactions, fluorine-fluorine interactions, π-CF interactions and hydrogen bonding. Furthermore, the MSPE method coupled with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) allowed for the rapid, sensitive, and accurate determination of ultra-trace PFAS in real water samples, human serum, and human follicular fluid. Under optimal conditions, the established MSPE method demonstrated a linear range (2 to 2000 ng L-1), with a correlation coefficient exceeding 0.9977, low limits of detection ranging from 0.54 to 1.47 ng L-1, with a relative standard deviation (RSD) < 9.1%. Additionally, the method showed excellent performance in complex real samples (recovery ratio of 81.7 to 121.6 %). The adsorption mechanism was investigated through kinetic, isotherm, and molecular simulation studies, revealing that the introduction of fluorine groups enhanced the hydrophobic interaction and fluorine-fluorine attraction between the adsorbent and PFAS. This work provides a proof-of-concept strategy for designing adsorbent materials with high efficiency and selectivity by post-modification, which has great potential for the detection and analysis of PFAS in complex samples.

Fluorinated Polydopamine Shell Decorated Fillers in Polytetrafluoroethylene Composite for Achieving Highly Reduced Coefficient of Thermal Expansion.

The noticeable difference in the coefficient of thermal expansion (CTE) for polytetrafluoroethylene (PTFE) coatings and copper substrates is a major challenge for thermal debonding of the copper-clad laminate (CCL) in high-frequency communications. Theoretically, ceramic fillers with low CTEs in the coating can effectively reduce the gap, and there remains a trade-off between the dispersibility of fillers and the interfacial interactions with the polymeric matrix. Here, we propose a novel approach to prepare a pentafluorobenzoyl chloride (PFBC)-modified polydopamine (PDA) shell on silica particles by using amidation. Such modified particles perform excellent dispersion and exhibit diminished interfacial gaps in the PTFE matrix, which highly reduces CTE to 77 ppm/°C, accounting for only 48.1% of the neat coating. Moreover, the composite exhibits enhanced mechanical strength and toughness, and consequently suppresses thermal debonding in CCL under high-temperature conditions. Therefore, results present a promising potential for its use in the next-generation CCL of high-frequency communication devices.

One-Pot Assembly of 2-Trifluoromethyl Benzothiazole and Benzoselenazole via Copper-Mediated Three-Component Cascade Reaction.

A domino one-pot synthesis of 2-(trifluoromethyl)benzothiazole via copper-mediated three-component cascade reaction starting from the easily accessible starting materials such as o-iodoanilines, methyl trifluoropyruvate, and elemental sulfur is reported. The present strategy displayed a comprehensive substrate scope and good functional group tolerance and enabled access to a variety of substituted 2-(trifluoromethyl)benzothiazoles. A 2-(trifluoromethyl)benzoselenazole has also been synthesized utilizing this reaction methodology.

A flexible nanofiber membrane containing dendritic oxygen probe for visual monitoring pressure distribution.

Pressure-sensitive paints (PSP) enable non-intrusive visualization of surface pressure distribution on model surface which is important for aerodynamic studies. However, conventional PSP materials suffer from photobleaching and inadequate sensitivity. In this work, we rationally designed and synthesized novel dendritic oxygen probes (PT1 and PT2) by covalently grafting fluorinated dendrons onto platinum tetrakis(pentafluorophenyl)porphyrin (PT0) (a common oxygen probe). Subsequently, PT2 loaded nanofibers membranes from polycaprolactone (PCL) were fabricated by electrospinning. Fabricated membranes showed high oxygen sensitivity (I0/I100 = 35.3) with excellent flexibility, good reversibility, and outstanding photostability (merely 2.0% intensity loss after prolonged irradiation). The pressure sensitivity was found around 0.73 % per kilopascal. Furthermore, significant variation in emission intensity with respect to the variation in air pressure (1.3-101.32 kPa), facilitates the naked eye visualization of the pressure distribution on the membrane surface. Such excellent oxygen and pressure sensitivity and photostability might be due to high fluorine contents of complex dendritic structure of PT2. This flexible fluorine-functionalized dendritic oxygen probe puts forward a facile and effective strategy to develop advanced PSP materials enabling accurate pressure mapping for aerodynamic studies.

Synthesis and Lewis Acid Properties of Neutral Silver(III) Adducts Containing the AgIII(CF3)3 Moiety.

The acetonitrile AgIII complex [AgIII(CF3)3(NCCH3)] (2) has been reported independently by Eujen and Naumann in the last century, albeit with intriguing NMR discrepancy. In their reports, 2 was claimed to be obtained starting from either [AgIII(CF3)3Cl]- (3.Cl) or [AgIII(CF3)4]- (1) via halide abstraction using AgNO3 or acidic treatment, resp. These two synthetic routes are herein reinvestigated. The feasibility of Naumann's method is demonstrated, thus providing 2 yet accompanied by its s-triazinyl derivative [AgIII(CF3)3(C6H9N3)] (2'). The formation of 2' is unprecedented and was thereby investigated. Both 2 and 2' were isolated in pure fashion and fully characterized. In turn, halide extraction from 3.Cl leads to the AgIII-ONO2 anion 5 instead of 2, as evidenced by NMR spectroscopy, EA and Sc-XRD.

Silver(i) Perfluoroalcoholates: Synthesis, Structure, and their Use as Transfer Reagents.

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.

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

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

4-Fluoro-benzyl (Z)-2-(2-oxoindolin-3-yl-idene)hydrazine-1-carbodi-thio-ate.

The title compound, C16H12FN3OS, a fluorinated di-thio-carbazate imine derivative, was synthesized by the one-pot, multi-component condensation reaction of hydrazine hydrate, carbon di-sulfide, 4-fluoro-benzyl chloride and isatin. The compound demonstrates near-planarity across much of the mol-ecule in the solid state and a Z configuration for the azomethine C=N bond. The Z form is further stabilized by the presence of an intra-molecular N-H⋯O hydrogen bond. In the extended structure, mol-ecules are linked into dimers by N-H⋯O hydrogen bonds and further connected into chains along either [20] or [100] by weak C-H⋯S and C-H⋯F hydrogen bonds, which further link into corrugated sheets and in combination form the overall three-dimensional network.

Value of 18 F-FDG PET/CT to Identify Occult Infection in Presumed Aseptic Pseudarthrosis after Spinal Fusion: Correlation with Intraoperative Cultures.

Objective Fluorine-18 fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) has gained attention as an emerging tool in case of suspicion of infection on spine, whether native or instrumented. However, the diagnostic performance of 18 F-FDG PET/CT in clinically occult low-grade surgical site infection (SSI) after spinal fusion, an important risk factor for pseudarthrosis, remains unknown. Methods We retrospectively identified all the presumed aseptic patients with pseudarthrosis confirmed by revision surgery who underwent preoperative 18 F-FDG PET/CT scans performed between April 2019 and November 2022. These patients were presumed aseptic because they did not have clinical signs or laboratory tests suggestive of SSI, preoperatively. The PET/CT images were analyzed in consensus by two nuclear medicine physicians blinded to the clinical, biological, and imaging information. Visual assessment of increased uptake around cage/intervertebral disk space (and/or hardware) higher than background recorded from the first normal adjacent vertebra was interpreted as positive. Image data were also quantitatively analyzed by the maximum standardized uptake value as an index of 18 F-FDG uptake, and the ratio between the uptake around cage/intervertebral disk space (and/or hardware) and background recorded from the first normal adjacent vertebra was calculated. The final diagnosis of infection was based on intraoperative cultures obtained during pseudarthrosis revision surgery. Results Thirty-six presumed aseptic patients with surgically confirmed pseudarthrosis after spinal fusion underwent preoperative 18 F-FDG PET/CT scans. Cultures of samples from revisions found that 20 patients (56%) were infected. The most frequent isolated bacterium was Cutibacterium acnes ( C. acnes ) in 15 patients (75%), followed by coagulase-negative staphylococci (CNS) in 7 patients (33%). Two patients had co-infections involving both C. acnes and CNS. Of the 36 PET/CT studied in this study, 12 scans were true-negative, 10 true-positive, 10 false-negative, and 4 false-positive. This resulted in sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 50%, 75%, 71%, 55%, and 61%, respectively. Conclusion In presumed aseptic pseudarthrosis after spinal fusion, 18 F-FDG PET/CT offers good specificity (75%) but low sensitivity (50%) to identify occult SSI. The high prevalence (56%) of SSI, mostly caused by C. acnes (75%), found in our presumed aseptic cohort of patients supports the utility of systematic intraoperative cultures in revision cases for pseudarthrosis.

The 18F-Difluoromethyl Group: Challenges, Impact and Outlook.

The difluoromethyl functionality has proven useful in drug discovery, as it can modulate the properties of bioactive molecules. For PET imaging, this structural motif has been largely underexploited in (pre)clinical radiotracers due to a lack of user-friendly radiosynthetic routes. This Minireview provides an overview of the challenges facing radiochemists and summarises the efforts made to date to access 18F-difluoromethyl-containing radiotracers. Two distinct approaches have prevailed, the first of which relies on 18F-fluorination. A second approach consists of a 18F-difluoromethylation process, which uses 18F-labelled reagents capable of releasing key reactive intermediates such as the [18F]CF2H radical or [18F]difluorocarbene. Finally, we provide an outlook for future directions in the radiosynthesis of [18F]CF2H compounds and their application in tracer radiosynthesis.

Identifying PFAS hotspots in surface waters of South Carolina using a new optimized total organic fluorine method and target LC-MS/MS.

Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants of concern due to their long persistence in the environment, toxicity, and widespread presence in humans and wildlife. Knowledge regarding the extent of PFAS contamination in the environment is limited due to the need for analytical methods that can reliably quantify all PFAS, since traditional target methods using liquid chromatography (LC)-mass spectrometry (MS) fail to capture many. For a more comprehensive analysis, a total organic fluorine (TOF) method can be used as a screening tool. We combined TOF analysis with target LC-MS/MS analysis to create a statewide PFAS hotspot map for surface waters throughout South Carolina. Thirty-eight of 40 locations sampled contained detectable concentrations of organic fluorine (above 100 ng/L). Of the 33 target PFAS analyzed using LC-MS/MS, the most prevalent were perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluoroheptanoic acid (PFHpA), and perfluorohexanesulfonate (PFHxS). On average, LC-MS/MS only accounted for 2 % of the TOF measured. Locations with high TOF did not necessarily correlate to high total quantified PFAS concentrations and vice-versa, demonstrating the limitations of target PFAS analysis and indicating that LC-MS may miss highly contaminated sites. Results suggest that future surveys should utilize TOF to more comprehensively capture PFAS in water bodies.

Sonochemical degradation of PFAS in ion exchange regeneration wastes.

One of the primary technologies currently being deployed for the removal of per- and polyfluoroalkyl substances (PFAS) from water is ion exchange (IX). For regenerable IX resins, concentrated PFAS in the resulting spent brine and/or still bottoms requires further treatment. This research demonstrated that PFAS in spent brine and still bottoms can be effectively degraded sonochemically at 1000 kHz. Overall, PFAS degradation was negatively impacted by high total organic carbon (TOC) and residual methanol (MeOH) solvent (up to 50 g/kg; 5% w:w), but was enhanced by the high chloride. The addition of caustic (up to 1 N NaOH) partially mitigated the inhibition by TOC and MeOH. Sonochemical degradation of individual PFAS compounds resulted in significant mineralization to form inorganic fluoride, but small quantities of volatile organic fluorine species (VOF) were noted. This is believed to be the first report of sonochemical degradation of PFAS in ion exchange regeneration wastes, and indicates the possibility for the application of this technology as part of a complete PFAS capture and destruction treatment train.

HFIP-mediated Desulfinative Friedel-Crafts Cyclobutenylation Reaction.

In 1,1,1,3,3,3-hexafluoroisopropyl alcohol (HFIP), gem-bis(triflyl)cyclobutenes, which can be prepared by the (2+2) cycloaddition reaction of Tf2C=CH2 with alkynes, underwent desulfination to generate the corresponding cyclobutenyl cation. This unique reactivity was successfully applied to the Friedel-Crafts type cyclobutenylation reaction of several (hetero)aromatic compounds.

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

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

Tuning Green Explosives through SNAr Chemistry.

Reactivity and regioselectivity of SNAr-type fluorine substitution with azide in polyfluoronitrobenzenes was studied both theoretically and experimentally. The obtained polyazidonitrobenzene derivatives were extensively characterized by NMR, IR, HPLC, X-ray, and DFT methods. It was found that the substitution with the azide nucleophile occurs first at the para- and the ortho-positions to the NO2-group and that transazidation reactions also occur here. Thermal decomposition of prepared azidonitrobenzenes was studied both in controlled (kinetic decay) and uncontrolled (explosion) modes. In case of the controlled thermal decomposition of ortho-azidonitrobenzenes, benzofuroxans were found as major products of the reaction unless another azido group was adjacent to the furoxan moiety. The bursting power of azidonitrobenzenes was found to rise gradually with the number of the azide substituents in the aromatic ring.

Synthesis of new representatives of A3B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations.

A carboranylporphyrin of A3B-type bearing a single pentafluorophenyl ring was prepared through the regioselective nucleophilic aromatic substitution reaction of the p-fluorine atoms in 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin with 9-mercapto-m-carborane. The reaction of this porphyrin with sodium azide led to the selective substitution of the p-fluorine atom in the pentafluorophenyl substituent with an azide functionality which upon reduction with SnCl2 resulted in the formation of the corresponding porphyrin with an amino group. Pentafluorophenyl-substituted A3B-porphyrins were studied and transformed to thiol and amino-substituted compounds allowing for the preparation of porphyrins with different reactive groups such as hydroxy and amino derivatives capable for further functionalization and conjugation of these porphyrins to other substrates. In addition, conjugates containing maleimide or biotin entities in the structure of carborane A3B-porphyrin were also synthesized based on the amino-substituted A3B-porphyrin. The structures of the prepared carboranylporphyrins were determined by UV-vis, IR, 1H, 19F, 11B NMR spectroscopic data and MALDI mass spectrometry.