Hexaphyrin as a Potential Theranostic Dye for Photothermal Therapy and 19F Magnetic Resonance Imaging

Two features of meso‐Aryl‐substituted expanded porphyrins suggest suitability as theranostic agents. They have excellent absorption in near infrared (NIR) region, and they offer the possibility of introduction of multiple fluorine atoms at structurally equivalent positions. Here, hexaphyrin (hexa) was synthesized from 2,6‐bis(trifluoromethyl)‐4‐formyl benzoate and pyrrole and evaluated as a novel expanded porphyrin with the above features. Under NIR illumination hexa showed intense photothermal and weak photodynamic effects, which were most likely due to its low excited states, close to singlet oxygen. The sustained photothermal effect caused ablation of cancer cells more effectively than the photodynamic effect of indocyanine green (a clinical dye). In addition, hexa showed potential for use in the visualization of tumors by ¹⁹F magnetic resonance imaging (MRI), because of the multiple fluorine atoms. Our results strongly support the utility of expanded porphyrins as theranostic agents in both photothermal therapy and ¹⁹F MRI.     

Perfluoro-tert-butyl Group-Derived Capmatinib: Synthesis,Biological Evaluation and Its Application in 19F Magnetic Resonance Imaging

Capmatinib is an FDA-approved drug to treat metastatic non-small cell lung cancer with MET-exon 14 skipping. Herein, the perfluoro-tert-butyl group, which possesses nine chemically identical fluorine atoms, was introduced on Capmatinib to afford a targeted ¹⁹F magnetic resonance imaging (MRI) probe, perfluoro-tert-butyl group-derived Capmatinib ( 9F-CAP ). The ¹⁹F MRI concentration limit was found to be 25 mM in FLASH sequence. Molecular docking simulation, surface plasmon resonance (SPR) (with a K_d of 40.7 μM), half-inhibitory concentration (with a IC₅₀ of 168 nM), Annexin V, and cytotoxicity assays jointly demonstrated that the 9F-CAP targeted cMET protein specifically. Therefore, the targeted imaging capability of 9F-CAP is of great significance for the preoperative diagnosis of specific cancers.     

Chemically modifiable fluorinated copolymer nanoparticles for 19F‐MRI contrast enhancement

Recently there has been interest in developing imaging contrast media for magnetic resonance imaging (MRI) that contain biologically rare, magnetically active nuclei such as fluorine. In principle, fluorinated contrast agents can be used to generate highly selective ¹⁹F magnetic resonance images that can be superimposed over complimentary ¹H magnetic resonance images to provide an anatomical context for the fluorinated contrast agent. Additionally, nanoparticles can be made to target various pathological sites via active and passive targeting mechanisms. In this study, fluorinated nanoparticles were produced using a free radical polymerization of vinyl formamide monomers with two different fluorinated monomers. The nanoparticles showed a clear, single ¹⁹F‐NMR signal. Additionally, surface amide groups were hydrolyzed to primary amines to yield additional surface reactivity. Fluorinated nanoparticles produced using a free‐radial polymerization method yield a new nanoparticle for ¹⁹F‐MRI applications with potential for facile functionalization. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

The properties of fluorine-containing diamond-like carbon films prepared by pulsed DC plasma-activated chemical vapour deposition

Diamond-like carbon films containing up to 23.1 at. % of fluorine (F-DLC), were deposited onto silicon substrates by low-frequency, pulsed DC, plasma-activated, chemical vapour deposition (PACVD). The influence of fluorine on plasma current density, deposition rate, composition, bonding structure, surface energy, hardness, stress and biocompatibility was investigated and correlated with the fluorine content. X-ray photoelectron spectroscopy (XPS) analysis revealed the presence C–C, C–CF and C–F for F-DLC films with a low fluorine concentration (1.5–12.1 at. %), however for films with a higher fluorine content (23.0 at. %) an additional peak due to CF₂ bonding was detected. The addition of fluorine into the DLC film resulted in lower stress and hardness values. The reduction in these values was attributed to the substitution of strong C=C by weaker C–F bonds which induces a decrease in hardness. Ion scattering spectrometery (ISS) measurements revealed the presence of fluorine atoms in the outmost layer of the F-DLC films and there was no evidence of surface oxygen contamination. The water contact angle was found to increase with increasing fluorine content and has been attributed to the change of the bonding nature in the films, in particularly increasing CF and CF₂ bonds. Biocompatibility tests performed using MG-63 osteoblast-like cell cultures indicated homogeneous and optimal tissue integration for both the DLC and the F-DLC surfaces. This pulsed-PACVD technique has been shown to produce biocompatible DLC and F-DLC coatings with a potential for large area applications.     

Compositional effects on the crosslink density of Ca–(Mg)–(Y)–Si–Al–oxyfluoronitride glasses

The effects of fluorine and nitrogen substitution for oxygen in aluminosilicate glasses, effectively oxyfluoronitride (OFN) glasses, modified by calcium, calcium–yttrium or calcium–magnesium on thermal and physical/mechanical properties have been compared. Thus, 42 glasses in the Ca–(Mg)–(Y)–Si–Al–O–(N)–(F) system have been prepared and characterized with respect to density (ρ), molar volume (MV), compactness (C), free volume (FV), glass transition temperatures measured by DTA (T_g,DTA) and dilatometry (T_g,dil), dilatometric softening point (T_DS), microhardness (μHv) and Young's modulus (E). Gradients of property variation with nitrogen or fluorine substitutions for oxygen are similar for all three different oxyfluoronitride glass systems and are comparable with those reported for other OFN glasses, again indicating independent and additive effects of nitrogen and fluorine. In attempting to further understand how fluorine affects the cross‐link density (CLD) in OFN glasses, it becomes apparent that it is necessary to allow for a greater contribution by aluminum in a modifier role as fluorine content is increased. This modified calculation of CLD values results in good linear fits between T_g and CLD values. This analysis clearly demonstrates and endorses the concepts that thermal properties are related to CLD while physical/mechanical properties are dependent on glass compactness.     

MOISTURE PROFILES IN A MODEL FOOD GEL DURING DRYING: MEASUREMENT USING MAGNETIC RESONANCE IMAGING AND EVALUATION OF THE HCKIAN MODEL

Magnetic resonance imaging (MRI) was used to obtain moisture profiles of a model food gel during drying. A cylinder of gel, 1 cm in diameter, with an initial moisture content of 76% was imaged while drying at room temperature. Moisture profiles were obtained from the imaging data by imaging calibration samples of known moisture content. Signal intensity of the images was found to be highly proportional to solids content. The moisture profiles were compared to profiles predicted by a finite difference solution of Fickian radial diffusion in a cylinder. Actual moisture profiles obtained by MRI were much flatter near the center of the cylinder, with a steeper moisture profile near the edge, compared to the typical parabolic shape of the Fickian model. The Fickian model was found to be an inaccurate predictor of the interior moisture profile of the model food gel, since effective diffusivity was found to not be solely a function of moisture content. The moisture profiles obtained provide for a method to evaluate other mass transfer models, and the methods outlined provide a technique to explore mass transfer within actual food materials during processing.     

Fluorine Gettering by Activated Charcoal in a Radiation Environment

Abstract

Activated charcoal has been shown to be an effective gettering agent for the fluorine gas that is liberated in a radiation environment. Even though activated charcoal is a commonly used getter, little is known about the radiation stability of the fluorine-charcoal product. This work has shown that not only is the product stable in high gamma radiation fields, but also that radiation enhances the capacity of the charcoal for the fluorine. The most useful application of this work is with the Molten Salt Reactor Experiment (MSRE) fuel salt because the radioactive components (fission products and actinides) cause radiolytic damage to the solid LiF-BeF²-ZrF⁴-UF⁴ (64.5, 30.3, 5.0, 0.13 mol %, respectively) resulting in the liberation of fluorine gas. This work has also demonstrated that the maximum damage to the fuel salt by ～3 × 10⁷ R/h gamma radiation is approximately 2%, at which point the the rate of recombination of fluorine with active metal sites within the salt lattice equals the rate of fluorine generation. The enhanced reactivity of the activated charcoal and radiation stability of the product ensures that the gettered fluorine will stay sequestered in the charcoal.     

Effects of fluorine doping on the electrochemical properties of LiV3O8 cathode material

A series of fluorine-doped lithium trivanadates LiV₃O_8−yF_z (z = 0, 0.03, 0.05, 0.1, 0.15, 0.2 and 0.5) were synthesized by the solid-state reaction. X-ray diffraction (XRD), Fourier transform infrared (FTIR) and scanning electron microscope (SEM) tests show that a proper amount of fluorine substituting for oxygen in LiV₃O₈ can modify its structure and surface morphology. Charge-discharge tests show that the doped samples with a proper amount of fluorine display good cycling stability, high coulombic efficiency and good rate capability, compared with undoped sample. The cyclic voltammetry (CV), area-specific impedance (ASI) and electrochemical impedance spectroscopy (EIS) tests indicate that the doped samples with a low fluorine content can stabilize the interface between the surface layer of the active particles and the electrolyte after cycling, while a high fluorine content form an unstable interface. The fluorine substitution is a convenient and effective method for improving the electrochemical performances of LiV₃O₈.     

A fluorine gas monitoring system for the direct oxy‐fluorination of polyethylene sheets

A new technique is presented to measure the concentration of fluorine in a reaction gas consisting of fluorine, nitrogen, and oxygen in a reaction chamber. The method is described as follows: The gas is directly taken from the chamber using a peristaltic pump and dissolved in a TISAB (total ionic strength adjusted buffer) solution. The concentration of fluorine ion is measured using the selected fluorine ion electrode, the output voltage of which is monitored. The concentration of the fluorine ion and the output voltage follow the Nernst relation so that the measurement of the output voltage of the system enables us to know the concentration of fluorine gas. This technique was applied to monitor the concentration of fluorine gas in the chamber in which a sheet of polyethylene nonwoven fabric was continuously oxy‐fluorinated. The monitored concentration of the fluorine gas as a function of time coincided with the variation of the incorporated fluorine in the sheet measured by X‐ray fluorescence (XRF) spectroscopy after the treatment. This technique can be best used for process control of the continuous oxy‐fluorination of polymeric materials. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 684–691, 2002     

Modes of occurrence of fluorine in the Late Paleozoic No. 6 coal from the Haerwusu Surface Mine, Inner Mongolia, China

The No. 6 coal from the Haerwusu Surface Mine, Inner Mongolia, China, is enriched in Al and Ga, which are valuable metal resources that could be extracted from fly ash. However, fluorine in the coal is unusually high (mean 286 μg/g) and potentially toxic to the environment in the extraction process. In this paper, a sequential extraction/density separation procedure (SE/DS) was designed to examine the modes of occurrence of fluorine in the coal. The results show that fluorine extracted in distilled water, NH₄Ac (1 mol/l), and HCl (0.5%) leachates is low, and that in sulfide fraction is below the detection limit. The organic and silicate associations are inferred to account for more than 90% of the total fluorine in the coal. Boehmite and kaolinite are prime carriers of fluorine (the fluorine content in silicate fraction of the boehmite-enriched sample H-14 is up to 1906 μg/g, and that of the kaolinite-enriched sample H-29 is 384 μg/g). In bench samples H-2 and H-3, a minor amount of fluorine is related to goyazite. The relationship between fluorine and boehmite indicates that they were probably derived from the sediment source region, the weathered bauxite of the uplifted Benxi Formation situated to the northeastern Jungar coalfield.     

部分进口煤炭中氟元素的含量特征及赋存形态

为加强对进口高氟煤炭的管理,评价进口煤炭中氟元素的环境迁入风险,采用高温燃烧水解-氟离子选择电极法对唐山港口岸进口的225批煤炭中的氟含量进行了测定;用稳健统计描述了其整体含量水平,并根据我国煤炭行业分级标准及富集比进行了质量评价;用相关分析对氟的赋存形态进行了分析。结果表明:唐山港口进口煤炭中的氟含量可描述为(137±24)mg/kg;按我国煤炭行业标准进行质量分级评价,唐山港口进口的68%的朝鲜煤、62%的加拿大煤属于中氟煤,氟含量算术平均值高于中国煤、世界煤,其迁入风险值得关注;进口朝鲜煤中氟含量与灰分、全硫含量呈中度正相关、与磷含量呈微弱正相关,推断氟的赋存形态主要为无机硫结合态(硫化物和硫酸盐)和黏土矿物,少部分可能存在于磷酸盐类矿物及有机硫结合态中;进口澳大利亚煤中氟含量与灰分、全硫含量相关性不显著,与磷含量呈低度正相关,推断氟的赋存形态比较复杂,可能部分以磷酸盐结合态存在,赋存于氟磷灰石、磷铝钙石中;进口加拿大煤中氟含量与灰分、全硫含量相关性不显著,与磷含量的相关性系数为0.763,显著性水平为0.01,表明二者呈高度正相关,具有显著性,说明二者有很强的伴生关系,推断氟主要以磷酸盐结合态存在,赋存于氟磷灰石、磷铝钙石中。     

Relationship between fluorine emission during firing of ceramic products and the firing temperature and composition of raw material

The fluorine content of clays from Lower Saxony and Bavaria was determined before and after firing. Although the mineral composition of the samples varied greatly, there was no evidence that any of the clay minerals contained significant amounts of fluorine. The amount of fluorine emitted within different temperature ranges during firing tests was determined for selected samples. Rates of temperature increase and heating times were also taken in consideration.A clear relationship between fluorine emission during firing and the Ca-content of the raw materials was demonstrated. Clays with low Ca-content started emitting fluorine at about 600°C; clays with a high Ca-content did not begin to release fluorine until 800°C. The addition of 10% CaCO₃ to a clay with a low Ca-content delayed the emission of fluorine until the higher temperature was reached.Because of the very low fluorine concentration in the raw materials, X-ray analysis could not be used to determine the compound in which calcium binds fluorine in the firing products. Tests with synthetic mixtures (NaF-CaCO₃ and NaF-CaCO₃-SiO₂) led to the conclusion that CaF₂ and various calciumfluorosilicates were involved.     

Properties of Ca–(Y)–Si–Al–O–N–F Glasses: Independent and Additive Effects of Fluorine and Nitrogen

Thirty glasses of composition (in equivalent percent) 20‐xCa:xY:50Si:30Al:(100‐y‐z)O:yN:zF, with x = 0, 10; y = 0, 10, 20, and z = 0, 1, 3, 5, 7 were prepared by melting and casting. All glasses were X‐ray amorphous. Glass molar volumes (MV) decreased with nitrogen substitution for oxygen for all fluorine contents and, correspondingly, glass fractional compactness increased. Fluorine substitution of oxygen had virtually no effect on molar volume or fractional glass compactness for the three nitrogen contents tested. Young's modulus and microhardness were virtually unaffected by fluorine substitution for oxygen while nitrogen substitution for oxygen caused increases in these two properties. Glass‐transition temperature and dilatometric‐softening point values all decreased with increasing fluorine substitution levels, while increasing nitrogen substitution caused values for these thermal properties to increase. Correspondingly, the thermal expansion coefficient increased with fluorine and decreased with nitrogen substitution levels. Using property value differences between glasses containing fluorine and the corresponding glass containing 0 eq.% F enabled 24 data points to be used to determine the effect of fluorine on T_g,dil and T_DS. The trends were linear with a gradient for both properties of the order of ?22°C (eq.% F)^?1. For the nitrogen effect, 20 data points were analyzed for trend effects. As expected from earlier work, all trends had good linearity. Gradients were for T_g,dil and T_DS +2.5°C (eq.% N)^?1, which are fairly similar to previous results in oxynitride systems. All of the data collected and its analysis clearly shows that the substitution effects of fluorine for oxygen and nitrogen for oxygen are independent and additive with the fluorine substitution. The property trends of the glasses are discussed in terms of their implications for glass structure.     

Application of a new modified epoxy adhesive for bonding fluorine rubber to metal

Adhesion of fluorine rubber to metals is an important issue. The aim of this work was to develop a new kind of adhesive for bonding fluorine rubber to metals. A new modified epoxy adhesive containing a special tackifier resin obtained from polysulfones with a high heat deflection temperature (HDT) was prepared. Study on the curing behavior of the adhesive was carried out. Properties of the adhesive and the effects of several main factors were studied by gelation time test, differential scanning calorimetry (DSC) and Fourier transform infrared (FT-IR) spectroscopy. The optimum amount of the tackifier resin was found to be 50 phr; the average tensile lap shear strength could be achieved to a level of 8–10 MPa. Infrared attenuated total reflection (IRATR) spectroscopy indicated that the tackifier resin accelerated the establishment of epoxy resin adhesion to steel, and also promoted bonding and vulcanization of fluorine rubber. Easy diffusion of cyanamide (decomposition compound of dicyandiamide (DICY) in the curing process) into epoxy resin and fluorine rubber facilitated the dissolution and reaction of DICY, and also promoted formation of complex bond between fluorine rubber and adhesive, hence an enhanced adhesion of fluorine rubber to metal was achieved.     

Analysis of partial suspension in stirred mixing cells using both MRI and ERT

Magnetic resonance imaging (MRI) and electrical resistance tomography (ERT) are collectively used to examine partial suspension of various glass and nylon particles in the same stirred baffled mixing cell of inner diameter 50 mm. Virtually complete suspension is observed to occur at critical agitation rates considerably lower than expected. Radial and axial particle concentration profiles, as measured using MRI and ERT, compare reasonably well. The higher resolution of MRI is able to detect concentration variations adjacent to the vessel wall whilst fillet formation of unsuspended solids is imaged at the base of the cell. To the best of our knowledge, this study represents the first direct comparison of MRI against ERT.     

A Compact and Synthetically Accessible Fluorine‐18 Labelled Cyclooctyne Prosthetic Group for Labelling of Biomolecules by Copper‐Free Click Chemistry

A new fluorine‐containing azadibenzocyclooctyne (ADIBO‐F) was designed using a synthetically accessible pathway. The fluorine‐18 prosthetic group was prepared from its toluenesulfonate precursor and isolated in 21–35 % radiochemical yield in 30 minutes of synthetic time. ADIBO‐F has been incorporated into azide‐functionalized, cancer‐targeting peptides through a strain‐promoted alkyne–azide cycloaddition with high radiochemical yields and purities. The final products are novel peptide‐based positron emission tomography (PET) imaging agents that possess high affinities for their targets, growth hormone secretagogue receptor 1a (GHSR‐1a) and gastrin‐releasing peptide receptor (GRPR), with IC₅₀ values of 9.7 and 0.50 nm , respectively. This is a new and rapid labelling option for the incorporation of fluorine‐18 into biomolecules for PET imaging.     

Effect of fluorine content on the crystallization and flexural strength of fluoro-mica glass ceramics

Two glasses with different contents of fluorine were fabricated. A single phase, KMg_3.25Si_3.625O₁₀F₂, precipitated in both of the glass samples after heat treatment. Both the crystallization activation energy (En) and the frequency factor (ν) increased with increasing fluorine content. This means that the fluorine content has a dual effect on the crystallization of fluorosilicic mica glass; the effect on the frequency factor is predominant. The flexural strength of the as-cerammed glass ceramic containing more fluorine is larger than that containing less fluorine when heated to the same temperature.     

Fluorinated a-C:H films investigated by thermal-induced gas effusion

Using thermal-induced gas effusion the decomposition of plasma deposited fluorinated a-C:H films has been investigated. The main contributions to the effusion spectra were found to come from hydrogen, hydrocarbons, CF₄ and HF. It is observed that hydrogen-related effusion is progressively substituted by the effusion of CF₄-related species as the fluorine content is increased, confirming that fluorine atoms substitute hydrogen in the amorphous network. At low fluorine contents (<10 at.%) the material is relatively compact and the effusion of hydrogen-related species (hydrogen molecules and hydrocarbons) dominate. For high enough fluorine concentrations a strong change in the effusion characteristics indicates that an interconnected network of voids is present. Strong effusion of CF₄-related species is found to be consistent with a surface desorption process and can be observed when CF_n bonds are present in the film microstructure and the void network dimensions are large enough, i.e. for films with the highest fluorine contents (∼20 at.%). The effusion results can be correlated to a structural transition from diamond-like to polymer-like film.     

Characterisation of fluorine containing glasses and glass-ceramics by 19F magic angle spinning nuclear magnetic resonance spectroscopy

¹⁹F magic angle spinning nuclear magnetic resonance (MAS-NMR) spectroscopy was used to characterise the local environment of fluorine in three types of fluorine containing glass-ceramics. The glass-ceramic compositions studied included four that crystallised to fluorcanasite, one which crystallised to barium fluorphlogopite and one which crystallised to fluorrichterite. In the fluorcanasite glasses, prior to crystallisation, the fluorine was present solely as an F–Ca(n) species whilst following crystallisation it was also present as an F–Ca(n) species in the fluorcanasite phase and in those glasses containing AlPO₄ it was also present as an F–Ca(n) species in fluorapatite.In the fluorrichterite and fluorphlogopite glasses the fluorine was present predominantly as F–Mg(3) and following crystallisation it was also present as F–Mg(3) in the fluorrichterite and fluorphlogopite phases. In all these glass-ceramics fluorine appears to be preferentially associated with the cations of highest charge to size ratio and the local environment of fluorine in the glass and the crystal phase is almost identical.     

Effect of Fluorine and Magnesium on the Polymorphism of Tricalcium Silicate: A New Fluorine-Containing Tricalcium Silicate Superlattice

There is evidence both by XRPD and by TEM electron diffraction of the presence of a new tricalcium silicate phase containing fluorine with triclinic cell parameters a = 2.32(7), b = 0.71(3), c = 1.28(3) nm, α= 106.5(3), β= 90(1), γ= 118(1)°. It is a superlattice of the rhombohedral C₃S, whose structure is probably deformed by the fluorine/oxygen substitution plus some calcium vacancies, the deformation being nevertheless smaller than that found in the triclinic polymorph of pure C₃S. Magnesium proves to have an effect additional to that observed for fluorine probably because it fixes the fluorine to the silicate lattice.