91 results on '"Fluorine chemistry"'
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2. F,N-Doped carbon dots as efficient Type I photosensitizers for photodynamic therapy.
- Author
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Wu X, Xu M, Wang S, Abbas K, Huang X, Zhang R, Tedesco AC, and Bi H
- Subjects
- Humans, Hep G2 Cells, Cell Survival drug effects, Photochemotherapy, Carbon chemistry, Carbon pharmacology, Photosensitizing Agents chemistry, Photosensitizing Agents pharmacology, Photosensitizing Agents chemical synthesis, Quantum Dots chemistry, Nitrogen chemistry, Fluorine chemistry
- Abstract
Photodynamic therapy (PDT) is a promising and emerging method for the treatment of cancer. Usually, Type II PDT is used in the clinic, and mainly involves three key elements: a photosensitizer, molecular oxygen and laser light. However, it is known that tumor tissue is deficient in oxygen molecules which is why Type I PDT is mostly preferred in the therapy of tumors in which the hypoxic tissue plays a major role. Fluorescent carbon dots (CDs) have shown great potential in cancer theranostics, acting as bioimaging agents and photosensitizers. Herein, we have synthesized novel kinds of fluorine and nitrogen co-doped carbon dots (F,NCDs) that emit bright green fluorescence under ultra-violet light. The F,NCDs have excellent water solubility and low cytotoxicity. They can generate hydroxyl radicals (˙OH) and superoxide anions (˙O
2 - ) under LED light (400-500 nm, 15 mW cm-2 ) irradiation, making them ideal photosensitizers for Type I PDT. Furthermore, upon using the HepG2 cell line as an in vitro model, the F,NCDs exhibit a better cell imaging effect and higher PDT efficiency than the control sample of CDs without F and N doping. This work has illustrated that the F,NCDs are promising in achieving the image-guided PDT of cancers, usually in a hypoxia tumor microenvironment.- Published
- 2022
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3. Why Is the Biodegradation of Polyfluorinated Compounds So Rare?
- Author
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Wackett LP
- Subjects
- Bacteria, Biodegradation, Environmental, Carbon chemistry, Fluorine chemistry, Phylogeny, Carbon metabolism, Fluorine metabolism
- Abstract
Thousands of heavily fluorinated chemicals are found in the environment, impact human and ecosystem health, and are relatively resistant to biological and chemical degradation. Their persistence in the environment is due to the inability of most microorganisms to biodegrade them. Only a very few examples of polyfluorinated compound biodegradation are known, and the reported rates are very low. This has been mostly attributed to the low chemical reactivity of the C-F bond. This Perspective goes beyond that explanation to highlight microbiological reasons why polyfluorinated compounds resist metabolism. The evolutionary and physiological impediments must be appreciated to better find, study, and harness microbes that degrade polyfluorinated compounds.
- Published
- 2021
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4. Phosphorus-mediated sp 2 -sp 3 couplings for C-H fluoroalkylation of azines.
- Author
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Zhang X, Nottingham KG, Patel C, Alegre-Requena JV, Levy JN, Paton RS, and McNally A
- Subjects
- Alkylation, Animals, Humans, Ligands, Pharmaceutical Preparations chemistry, Pharmacokinetics, Phosphines chemistry, Carbon chemistry, Fluorine chemistry, Hydrogen chemistry, Phosphorus chemistry, Pyridines chemistry
- Abstract
Fluoroalkyl groups profoundly affect the physical properties of pharmaceuticals and influence almost all metrics associated with their pharmacokinetic and pharmacodynamic profile
1-4 . Drug candidates increasingly contain trifluoromethyl (CF3 ) and difluoromethyl (CF2 H) groups, and the same trend in agrochemical development shows that the effect of fluoroalkylation translates across human, insect and plant life5,6 . New fluoroalkylation reactions have undoubtedly stimulated this shift; however, methods that directly convert C-H bonds into C-CF2 X groups (where X is F or H) in complex drug-like molecules are rare7-13 . Pyridines are the most common aromatic heterocycles in pharmaceuticals14 , but only one approach-via fluoroalkyl radicals-is viable for achieving pyridyl C-H fluoroalkylation in the elaborate structures encountered during drug development15-17 . Here we develop a set of bench-stable fluoroalkylphosphines that directly convert the C-H bonds in pyridine building blocks, drug-like fragments and pharmaceuticals into fluoroalkyl derivatives. No preinstalled functional groups or directing groups are required. The reaction tolerates a variety of sterically and electronically distinct pyridines, and is exclusively selective for the 4-position in most cases. The reaction proceeds through initial formation of phosphonium salts followed by sp2 -sp3 coupling of phosphorus ligands-an underdeveloped manifold for forming C-C bonds.- Published
- 2021
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5. Bifunctional Nitrogen and Fluorine Co-doped Carbon Dots as Fluorescence Probe for Silicon and Mercury by pH Switching.
- Author
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Tabaraki R and Rahmatinya Z
- Subjects
- Hydrogen-Ion Concentration, Spectrometry, Fluorescence, Limit of Detection, Carbon chemistry, Mercury analysis, Fluorescent Dyes chemistry, Fluorescent Dyes chemical synthesis, Nitrogen chemistry, Quantum Dots chemistry, Silicon chemistry, Fluorine chemistry
- Abstract
New nitrogen and fluorine co-doped carbon dots were synthesized and used as a dual function fluorescent probe for silicon and mercury ions. The size of CDs was 10 nm. At optimum conditions (pH = 13, λ
ex = 360 nm, and λem = 518 nm), the detection limit (DL) of silicon was 16.6 nM. Linear calibration was observed in the range of 0.8-35 µM. This fluorescence probe for silicon detection is presented for the first time and had the lowest detection limit in comparison with different previously reported techniques. In addition to the above property, these co-doped carbon dots had the second function as a fluorescence probe for mercury detection at pH = 8. The DL for mercury was 38 nM. The performance of this probe was also compared with other co-doped carbon dots. Excellent sensitivity and selectivity, simple method, low-cost materials, and applicability in real sample analysis are advantages of this dual function fluorescence probe.- Published
- 2021
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6. Formation of Monofluorinated Radical Cofactor in Galactose Oxidase through Copper-Mediated C-F Bond Scission.
- Author
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Li J, Davis I, Griffith WP, and Liu A
- Subjects
- Catalysis, Crystallography, X-Ray, Directed Molecular Evolution, Electron Spin Resonance Spectroscopy, Galactose Oxidase chemistry, Galactose Oxidase genetics, Kinetics, Ligands, Mutagenesis, Site-Directed, Oxidation-Reduction, Protein Structure, Tertiary, Tyrosine analogs & derivatives, Tyrosine metabolism, Carbon chemistry, Copper chemistry, Fluorine chemistry, Free Radicals chemistry, Galactose Oxidase metabolism, Tyrosine chemistry
- Abstract
Galactose oxidase (GAO) contains a Cu(II)-ligand radical cofactor. The cofactor, which is autocatalytically generated through the oxidation of the copper, consists of a cysteine-tyrosine radical (Cys-Tyr
• ) as a copper ligand. The formation of the cross-linked thioether bond is accompanied by a C-H bond scission on Tyr272 with few details known thus far. Here, we report the genetic incorporation of 3,5-dichlorotyrosine (Cl2 -Tyr) and 3,5-difluorotyrosine (F2 -Tyr) to replace Tyr272 in the GAOV previously optimized for expression through directed evolution. The proteins with an unnatural tyrosine residue are catalytically competent. We determined the high-resolution crystal structures of the GAOV , Cl2 -Tyr272, and F2 -Tyr272 incorporated variants at 1.48, 1.23, and 1.80 Å resolution, respectively. The structural data showed only one halogen remained in the cofactor, indicating that an oxidative carbon-chlorine/fluorine bond scission has occurred during the autocatalytic process of cofactor biogenesis. Using hydroxyurea as a radical scavenger, the spin-coupled hidden Cu(II) was observed by EPR spectroscopy. Thus, the structurally defined catalytic center with genetic unnatural tyrosine substitution is in the radical containing form as in the wild-type, i.e., Cu(II)-(Cl-Tyr• -Cys) or Cu(II)-(F-Tyr• -Cys). These findings illustrate a previously unobserved C-F/C-Cl bond cleavage in biology mediated by a mononuclear copper center.- Published
- 2020
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7. Carbon-fluorine bond cleavage mediated by metalloenzymes.
- Author
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Wang Y and Liu A
- Subjects
- Carbon chemistry, Fluorine chemistry, Metalloproteins chemistry, Carbon metabolism, Fluorine metabolism, Metalloproteins metabolism
- Abstract
Fluorochemicals are a widely distributed class of compounds and have been utilized across a wide range of industries for decades. Given the environmental toxicity and adverse health threats of some fluorochemicals, the development of new methods for their decomposition is significant to public health. However, the carbon-fluorine (C-F) bond is among the most chemically robust bonds; consequently, the degradation of fluorinated hydrocarbons is exceptionally difficult. Here, metalloenzymes that catalyze the cleavage of this chemically challenging bond are reviewed. These enzymes include histidine-ligated heme-dependent dehaloperoxidase and tyrosine hydroxylase, thiolate-ligated heme-dependent cytochrome P450, and four nonheme oxygenases, namely, tetrahydrobiopterin-dependent aromatic amino acid hydroxylase, 2-oxoglutarate-dependent hydroxylase, Rieske dioxygenase, and thiol dioxygenase. While much of the literature regarding the aforementioned enzymes highlights their ability to catalyze C-H bond activation and functionalization, in many cases, the C-F bond cleavage has been shown to occur on fluorinated substrates. A copper-dependent laccase-mediated system representing an unnatural radical defluorination approach is also described. Detailed discussions on the structure-function relationships and catalytic mechanisms provide insights into biocatalytic defluorination, which may inspire drug design considerations and environmental remediation of halogenated contaminants.
- Published
- 2020
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8. Desymmetrization of difluoromethylene groups by C-F bond activation.
- Author
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Butcher TW, Yang JL, Amberg WM, Watkins NB, Wilkinson ND, and Hartwig JF
- Subjects
- Alkenes chemistry, Catalysis, Cations, Halogenation, Hydrogen chemistry, Iridium chemistry, Organophosphorus Compounds chemistry, Oxidation-Reduction, Palladium chemistry, Carbon chemistry, Fluorine chemistry
- Abstract
Tertiary stereogenic centres containing one fluorine atom are valuable for medicinal chemistry because they mimic common tertiary stereogenic centres containing one hydrogen atom, but they possess distinct charge distribution, lipophilicity, conformation and metabolic stability
1-3 . Although tertiary stereogenic centres containing one hydrogen atom are often set by enantioselective desymmetrization reactions at one of the two carbon-hydrogen (C-H) bonds of a methylene group, tertiary stereocentres containing fluorine have not yet been constructed by the analogous desymmetrization reaction at one of the two carbon-fluorine (C-F) bonds of a difluoromethylene group3 . Fluorine atoms are similar in size to hydrogen atoms but have distinct electronic properties, causing C-F bonds to be exceptionally strong and geminal C-F bonds to strengthen one another4 . Thus, exhaustive defluorination typically dominates over the selective replacement of a single C-F bond, hindering the development of the enantioselective substitution of one fluorine atom to form a stereogenic centre5,6 . Here we report the catalytic, enantioselective activation of a single C-F bond in an allylic difluoromethylene group to provide a broad range of products containing a monofluorinated tertiary stereogenic centre. By combining a tailored chiral iridium phosphoramidite catalyst, which controls regioselectivity, chemoselectivity and enantioselectivity, with a fluorophilic activator, which assists the oxidative addition of the C-F bond, these reactions occur in high yield and selectivity. The design principles proposed in this work extend to palladium-catalysed benzylic substitution, demonstrating the generality of the approach.- Published
- 2020
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9. Be cautious applying carbon-fluorine bonds in drug delivery.
- Author
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Sonne C, Lam SS, Kim KH, Rinklebe J, and Ok YS
- Subjects
- Fluorides, Fluorocarbons, Humans, Carbon chemistry, Drug Delivery Systems, Fluorine chemistry
- Abstract
As reported in Chemosphere by Colles et al. (2020), there are multiple pathways for human exposure to poly- and perfluoroalkyl substances (PFAS). Now, a new chemical formation of C-F bonds in drug delivery lead to concerns for human exposure as these inert chemical formations are resistance to metabolic degradation and excretion., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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10. Quantification of Uncoupled Spin Domains in Spin-Abundant Disordered Solids.
- Author
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Walder BJ and Alam TM
- Subjects
- Algorithms, Fluorine chemistry, Fluorocarbon Polymers chemistry, Graphite chemistry, Limit of Detection, Materials Testing, Petroleum, Programming Languages, Reproducibility of Results, Carbon chemistry, Magnetic Resonance Spectroscopy methods, Signal Processing, Computer-Assisted
- Abstract
Materials often contain minor heterogeneous phases that are difficult to characterize yet nonetheless significantly influence important properties. Here we describe a solid-state NMR strategy for quantifying minor heterogenous sample regions containing dilute, essentially uncoupled nuclei in materials where the remaining nuclei experience heteronuclear dipolar couplings. NMR signals from the coupled nuclei are dephased while NMR signals from the uncoupled nuclei can be amplified by one or two orders of magnitude using Carr-Meiboom-Purcell-Gill (CPMG) acquisition. The signal amplification by CPMG can be estimated allowing the concentration of the uncoupled spin regions to be determined even when direct observation of the uncoupled spin NMR signal in a single pulse experiment would require an impractically long duration of signal averaging. We use this method to quantify residual graphitic carbon using
13 C CPMG NMR in poly(carbon monofluoride) samples synthesized by direct fluorination of carbon from various sources. Our detection limit for graphitic carbon in these materials is better than 0.05 mol%. The accuracy of the method is discussed and comparisons to other methods are drawn.- Published
- 2020
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11. Late-stage oxidative C(sp 3 )-H methylation.
- Author
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Feng K, Quevedo RE, Kohrt JT, Oderinde MS, Reilly U, and White MC
- Subjects
- Androstenes chemical synthesis, Androstenes chemistry, Catalysis, Drug Inverse Agonism, Electrons, Fluorine chemistry, Hydroxylation, Lewis Acids chemistry, Manganese chemistry, Methylation, Nuclear Receptor Subfamily 1, Group F, Member 3 agonists, Nuclear Receptor Subfamily 1, Group F, Member 3 antagonists & inhibitors, Oxazolidinones chemical synthesis, Oxazolidinones chemistry, Oxidation-Reduction, Sphingosine-1-Phosphate Receptors antagonists & inhibitors, Tetrazoles chemical synthesis, Tetrazoles chemistry, Biological Products chemical synthesis, Biological Products chemistry, Carbon chemistry, Chemistry Techniques, Synthetic, Hydrogen chemistry, Pharmaceutical Preparations chemical synthesis, Pharmaceutical Preparations chemistry
- Abstract
Frequently referred to as the 'magic methyl effect', the installation of methyl groups-especially adjacent (α) to heteroatoms-has been shown to dramatically increase the potency of biologically active molecules
1-3 . However, existing methylation methods show limited scope and have not been demonstrated in complex settings1 . Here we report a regioselective and chemoselective oxidative C(sp3 )-H methylation method that is compatible with late-stage functionalization of drug scaffolds and natural products. This combines a highly site-selective and chemoselective C-H hydroxylation with a mild, functional-group-tolerant methylation. Using a small-molecule manganese catalyst, Mn(CF3 PDP), at low loading (at a substrate/catalyst ratio of 200) affords targeted C-H hydroxylation on heterocyclic cores, while preserving electron-neutral and electron-rich aryls. Fluorine- or Lewis-acid-assisted formation of reactive iminium or oxonium intermediates enables the use of a mildly nucleophilic organoaluminium methylating reagent that preserves other electrophilic functionalities on the substrate. We show this late-stage C(sp3 )-H methylation on 41 substrates housing 16 different medicinally important cores that include electron-rich aryls, heterocycles, carbonyls and amines. Eighteen pharmacologically relevant molecules with competing sites-including drugs (for example, tedizolid) and natural products-are methylated site-selectively at the most electron rich, least sterically hindered position. We demonstrate the syntheses of two magic methyl substrates-an inverse agonist for the nuclear receptor RORc and an antagonist of the sphingosine-1-phosphate receptor-1-via late-stage methylation from the drug or its advanced precursor. We also show a remote methylation of the B-ring carbocycle of an abiraterone analogue. The ability to methylate such complex molecules at late stages will reduce synthetic effort and thereby expedite broader exploration of the magic methyl effect in pursuit of new small-molecule therapeutics and chemical probes.- Published
- 2020
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12. Fluorine-Doped Carbon Dots with Intrinsic Nucleus-Targeting Ability for Drug and Dye Delivery.
- Author
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Gao P, Liu S, Su Y, Zheng M, and Xie Z
- Subjects
- Aziridines chemistry, Biological Transport, Coloring Agents chemistry, Drug Carriers chemistry, HeLa Cells, Humans, Nanoparticles chemistry, Solvents chemistry, Boron Compounds chemistry, Boron Compounds metabolism, Carbon chemistry, Cell Nucleus metabolism, Doxorubicin chemistry, Doxorubicin metabolism, Fluorine chemistry
- Abstract
A new type of fluorine-doped carbon dots (FCDs) with the nucleus-targeting capability was prepared and utilized as a promising candidate for drug and dye delivery. Doxorubicin (DOX) and boron dipyrromethene (BODIPY) was used as a model drug and dye, respectively, to construct FCD-DOX and FCD-BODIPY nanocomposites via coassembly with FCDs. The results demonstrate that FCDs can remarkably increase the cellular uptake and delivery of DOX and BODIPY. This work developed a convenient strategy to construct CDs-based nanohybrids for nucleus-targeted bioimaging and cancer treatment.
- Published
- 2020
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13. Tritiodefluorination of alkyl C-F groups.
- Author
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Brož B and Marek A
- Subjects
- Alkylation, Isotope Labeling, Oxidation-Reduction, Carbon chemistry, Fluorine chemistry, Halogenation, Tritium chemistry
- Abstract
A straightforward methodology of fluorine substitution by tritium/deuterium is reported. The described method is selective towards the F─C (sp
3 ) group and leaves both the aromatic F─C (sp2 ) and F2 ─C (sp3 ) moieties unaffected. Alkylfluorides, readily synthesized from appropriate alcohols by treatment with diethylaminosulfur trifluoride (DAST) reagent in an overall yield up to 76%, undergoes activation with the boron-based Lewis acid B(C6 F5 )3 , and stoichiometric in situ reduction with a tritide/deuteride reagent-the [TMP2(3) H][2(3) HB(C6 F5 )3 ] system of frustrated Lewis pair. This methodology provides an isolated yield of up to 93% of regio-specifically labeled small organic compounds with superior2 H-enrichment of over 95%. The specific activity of prepared 1-(2-[3 H]-ethyl)naphthalene was determined at 29.0 Ci/mmol. The site selectivity of the Lewis acid/ [TMP2(3) H][2(3) HB(C6 F5 )3 ] approach is orthogonal to currently used methods and allows for isotopic labeling of complementary positions in molecules. Reported labeling methodology proceeds well at ultra-mild reaction conditions (220 mbar of T2 ), allowing very low consumption of the radioactive source (4.2 Ci/156 GBq), and producing limited amount of radioactive waste., (© 2019 John Wiley & Sons, Ltd.)- Published
- 2019
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14. A Novel Application of Fluorine Doped Carbon Dots Combining Vortex-Assisted Liquid-Liquid Microextraction for Determination of 4-Nitrophenol with Spectrofluorimetric Method.
- Author
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Feng S, Mu Z, Liu H, Huang J, Li X, and Yang Y
- Subjects
- Fluorometry, Water Pollutants, Chemical chemistry, Carbon chemistry, Fluorine chemistry, Liquid Phase Microextraction, Nitrophenols analysis, Quantum Dots chemistry
- Abstract
A simple and fast vortex-assisted liquid-liquid microextraction (VA-LLME) combining with fluorescent carbon dots have been developed for the determination 4-nitrophenol (4-NP). The high fluorescent quantum yield (58.9%) fluorine doped carbon dots (F-CDs) were synthesized using tetrafluoroterephthalic acid as a fluorine source and using citric acid as a fluorine source and using ethylenediamine as a nitrogen source via a one-step hydrothermal method. F-CDs fluorescence was effectively quenched by 4-NP due to inner filter effect (IFE) and the strong interactions between functional groups (-COOH,-OH, -NH
2 and -F groups) of the F-CDs and 4-NP. In VALLME method, n-octanol was employed as extraction solvent, and vortex-mix was exploited as a gentle mix method to reduce emulsification time and improve the extraction efficiency. The detection limits, the quantification limit and relative standard deviation for the 4-NP were found as 15 nM, 50 nM and 3.5%, respectively. Moreover, the obtained F-CDs can be employed as fluorescent probe to detect 4-NP in real environmental water samples.- Published
- 2019
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15. Fluorine and Nitrogen Co-Doped Carbon Dot Complexation with Fe(III) as a T 1 Contrast Agent for Magnetic Resonance Imaging.
- Author
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Wang J, Hu X, Ding H, Huang X, Xu M, Li Z, Wang D, Yan X, Lu Y, Xu Y, Chen Y, Morais PC, Tian Y, Zhang RQ, and Bi H
- Subjects
- Animals, HeLa Cells, Humans, Mice, Mice, Inbred BALB C, Neoplasms, Experimental metabolism, Neoplasms, Experimental pathology, Carbon chemistry, Carbon pharmacology, Contrast Media chemistry, Contrast Media pharmacology, Ferric Compounds chemistry, Ferric Compounds pharmacology, Fluorine chemistry, Fluorine pharmacology, Magnetic Resonance Imaging, Nanoparticles chemistry, Nanoparticles therapeutic use, Neoplasms, Experimental diagnostic imaging, Nitrogen chemistry, Nitrogen pharmacology
- Abstract
Commercial gadolinium-based materials have been widely used as contrast agents for magnetic resonance imaging (MRI), but the high toxicity of leaking free Gd
3+ ions still raises biosafety concerns. Here, we develop a novel, safe, and efficient MRI contrast agent based on a stable Fe(III) complex of fluorine and nitrogen co-doped carbon dots (F,N-CDs) that was prepared from glucose and levofloxacin by a simple microwave-assisted thermal decomposition method. The obtained Fe3+ @F,N-CD complex exhibits higher longitudinal relaxivity ( r1 = 5.79 mM-1 ·s-1 ) than that of the control samples of the Fe3+ @CD complex ( r1 = 4.23 mM-1 s-1 ) and free Fe3+ ( r1 = 1.59 mM-1 s-1 ) in aqueous solution, as assessed by a 1.5 T NMR analyzer. More importantly, the Fe3+ @F,N-CD complex is very stable with a large coordination constant of 1.06 × 107 in aqueous medium. While incubated with HeLa cells, the Fe3+ @F,N-CD complex shows clear MR images, demonstrating that it has potential to be an excellent MRI contrast agent. Furthermore, in vivo MRI experiments indicate that the Fe3+ @F,N-CD complex provides high-resolution MRI pictures of 4T1 tumor bearing BALB/c mice 15 min after injection and can be completely excreted 2 h after administration. No cytotoxicity was observed with F,N-CDs and Fe concentration up to 0.2 mg/mL and 0.3 mM in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assay, respectively. The possible mechanism of the enhanced MRI effect of the Fe3+ @F,N-CD complex is therefore proposed. The extremely low toxicity, high r1 relaxivity, strong photoluminescence, and low synthetic cost enable the Fe3+ @F,N-CD complex to be a safe and promising T1 -weighted MRI contrast agent for clinical applications.- Published
- 2019
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16. Calculations of 13 C NMR chemical shifts and F-C coupling constants of ciprofloxacin.
- Author
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Koch A, Stamboliyska B, Mikhova B, Breznica-Selmani P, Mladenovska K, and Popovski E
- Subjects
- Carbon-13 Magnetic Resonance Spectroscopy standards, Density Functional Theory, Reference Standards, Carbon chemistry, Ciprofloxacin chemistry, Fluorine chemistry
- Abstract
Ciprofloxacin is a widely used fluoroquinolone antibiotic. In this work, a comprehensive evaluation of MP2 and DFT with different functionals and basis sets was carried out to select the most suitable level of theory for the study of the NMR properties of ciprofloxacin. Their relative predictive capabilities were evaluated comparing the theoretically predicted and experimental spectral data. Our computational results indicated that in contrast to the solid state, the molecule of ciprofloxacin does not exist as a zwitterion in gaseous state. The results of the calculations of the chemical shifts most close to the experimental were obtained with B3LYP/aug-cc-pVDZ. The F-C coupling constants were calculated systematically with different DFT methods and several basis sets. In general, the calculations of the coupling constants with the BHandH computational method including the applied in this work 6-311++G**, EPRII, and EPRIII basis sets showed a good reproducibility of the experimental values of the coupling constants., (© 2019 John Wiley & Sons, Ltd.)
- Published
- 2019
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17. Cleavage of a carbon-fluorine bond by an engineered cysteine dioxygenase.
- Author
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Li J, Griffith WP, Davis I, Shin I, Wang J, Li F, Wang Y, Wherritt DJ, and Liu A
- Subjects
- Biocatalysis, Carbon chemistry, Crystallography, X-Ray, Cysteine Dioxygenase analysis, Fluorine chemistry, Humans, Models, Molecular, Carbon metabolism, Cysteine Dioxygenase metabolism, Fluorine metabolism, Protein Engineering
- Abstract
Cysteine dioxygenase (CDO) plays an essential role in sulfur metabolism by regulating homeostatic levels of cysteine. Human CDO contains a post-translationally generated Cys93-Tyr157 cross-linked cofactor. Here, we investigated this Cys-Tyr cross-linking by incorporating unnatural tyrosines in place of Tyr157 via a genetic method. The catalytically active variants were obtained with a thioether bond between Cys93 and the halogen-substituted Tyr157, and we determined the crystal structures of both wild-type and engineered CDO variants in the purely uncross-linked form and with a mature cofactor. Along with mass spectrometry and
19 F NMR, these data indicated that the enzyme could catalyze oxidative C-F or C-Cl bond cleavage, resulting in a substantial conformational change of both Cys93 and Tyr157 during cofactor assembly. These findings provide insights into the mechanism of Cys-Tyr cofactor biogenesis and may aid the development of bioinspired aromatic carbon-halogen bond activation.- Published
- 2018
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18. Modern Approaches for Asymmetric Construction of Carbon-Fluorine Quaternary Stereogenic Centers: Synthetic Challenges and Pharmaceutical Needs.
- Author
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Zhu Y, Han J, Wang J, Shibata N, Sodeoka M, Soloshonok VA, Coelho JAS, and Toste FD
- Subjects
- Alkylation, Catalysis, Coordination Complexes chemistry, Halogenation, Molecular Structure, Stereoisomerism, Transition Elements chemistry, Carbon chemistry, Chemistry Techniques, Synthetic methods, Fluorine chemistry, Pharmaceutical Preparations chemistry
- Abstract
New methods for preparation of tailor-made fluorine-containing compounds are in extremely high demand in nearly every sector of chemical industry. The asymmetric construction of quaternary C-F stereogenic centers is the most synthetically challenging and, consequently, the least developed area of research. As a reflection of this apparent methodological deficit, pharmaceutical drugs featuring C-F stereogenic centers constitute less than 1% of all fluorine-containing medicines currently on the market or in clinical development. Here we provide a comprehensive review of current research activity in this area, including such general directions as asymmetric electrophilic fluorination via organocatalytic and transition-metal catalyzed reactions, asymmetric elaboration of fluorine-containing substrates via alkylations, Mannich, Michael, and aldol additions, cross-coupling reactions, and biocatalytic approaches.
- Published
- 2018
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19. Palladium-catalysed electrophilic aromatic C-H fluorination.
- Author
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Yamamoto K, Li J, Garber JAO, Rolfes JD, Boursalian GB, Borghs JC, Genicot C, Jacq J, van Gastel M, Neese F, and Ritter T
- Subjects
- Blood-Brain Barrier, Catalysis, Indicators and Reagents chemistry, Pharmaceutical Preparations chemistry, Carbon chemistry, Fluorine chemistry, Halogenation, Hydrogen chemistry, Palladium chemistry
- Abstract
Aryl fluorides are widely used in the pharmaceutical and agrochemical industries, and recent advances have enabled their synthesis through the conversion of various functional groups. However, there is a lack of general methods for direct aromatic carbon-hydrogen (C-H) fluorination. Conventional methods require the use of either strong fluorinating reagents, which are often unselective and difficult to handle, such as elemental fluorine, or less reactive reagents that attack only the most activated arenes, which reduces the substrate scope. A method for the direct fluorination of aromatic C-H bonds could facilitate access to fluorinated derivatives of functional molecules that would otherwise be difficult to produce. For example, drug candidates with improved properties, such as increased metabolic stability or better blood-brain-barrier penetration, may become available. Here we describe an approach to catalysis and the resulting development of an undirected, palladium-catalysed method for aromatic C-H fluorination using mild electrophilic fluorinating reagents. The reaction involves a mode of catalysis that is unusual in aromatic C-H functionalization because no organometallic intermediate is formed; instead, a reactive transition-metal-fluoride electrophile is generated catalytically for the fluorination of arenes that do not otherwise react with mild fluorinating reagents. The scope and functional-group tolerance of this reaction could provide access to functional fluorinated molecules in pharmaceutical and agrochemical development that would otherwise not be readily accessible.
- Published
- 2018
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20. Intramolecular C-H and C-F Bond Oxygenation Mediated by a Putative Terminal Oxo Species in Tetranuclear Iron Complexes.
- Author
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de Ruiter G, Thompson NB, Takase MK, and Agapie T
- Subjects
- Ligands, Models, Molecular, Carbon chemistry, Fluorine chemistry, Hydrogen chemistry, Iron chemistry, Macromolecular Substances chemistry
- Abstract
Herein we report the intramolecular arene C-H and C-F bond oxygenation by tetranuclear iron complexes. Treatment of [LFe3(PhPz)3OFe][OTf]2 (1) or its fluorinated analog [LFe3(F2ArPz)3OFe][OTf]2 (5) with iodosobenzene results in the regioselective hydroxylation of a bridging pyrazolate ligand, converting a C-H or C-F bond into a C-O bond. The observed reactivity suggests the formation of terminal and reactive Fe-oxo intermediates. With the possibility of intramolecular electron transfer within clusters in 1 and 5, different reaction pathways (Fe(IV)-oxo vs Fe(III)-oxo) might be responsible for the observed arene hydroxylation.
- Published
- 2016
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21. An organocatalytic strategy for the stereoselective synthesis of C-galactosides with fluorine at the pseudoanomeric carbon.
- Author
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Altiti AS, Bachan S, Alrowhani W, and Mootoo DR
- Subjects
- Aldehydes chemical synthesis, Aldehydes chemistry, Catalysis, Crystallography, X-Ray, Models, Molecular, Molecular Conformation, Stereoisomerism, Carbon chemistry, Fluorine chemistry, Galactosides chemical synthesis, Galactosides chemistry, Proline chemistry
- Abstract
The α-fluorination of α- and β-C-ethanals of galactose using Jørgensen catalysts and NFSI was investigated. The crude reaction products were transformed to their primary alcohol or methylenated derivatives, which are versatile precursors to biologically interesting fluorinated glycomimetics. The α-C-glycoside substrate gave moderate to high yields of fluorinated α-C-glycosides with minor amounts of β-C-glycoside analogues. The reactions on the β-C-glycoside were lower yielding but gave exclusively fluorinated β-C-glycosides. For both α- and β-C-glycoside substrates (R) and (S) catalyst showed complementary stereoselectivity. The preparation of difluorinated materials required the use of racemic catalyst as enantiomerically pure catalyst gave intractable mixtures of products. These results are in line with the results for simple achiral aldehydes, and suggest that stereochemistry in the reactions of these chiral, highly substituted, carbohydrate-derived aldehydes are controlled primarily by the chirality in the catalyst.
- Published
- 2015
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22. Highly Efficient C-SeCF3 Coupling of Aryl Iodides Enabled by an Air-Stable Dinuclear Pd(I) Catalyst.
- Author
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Aufiero M, Sperger T, Tsang AS, and Schoenebeck F
- Subjects
- Catalysis, Models, Molecular, Molecular Structure, Carbon chemistry, Hydrocarbons, Iodinated chemistry, Organometallic Compounds chemistry, Palladium chemistry, Selenium chemistry
- Abstract
Building on our recent disclosure of catalysis at dinuclear Pd(I) sites, we herein report the application of this concept to the realization of the first catalytic method to convert aryl iodides into the corresponding ArSeCF3 compounds. Highly efficient C-SeCF3 coupling of a range of aryl iodides was achieved, enabled by an air-, moisture-, and thermally stable dinuclear Pd(I) catalyst. The novel SeCF3 -bridged dinuclear Pd(I) complex 3 was isolated, studied for its catalytic competence and shown to be recoverable. Experimental and computational data are presented in support of dinuclear Pd(I) catalysis., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2015
- Full Text
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23. Electronic structures and current conductivities of B, C, N and F defects in amorphous titanium dioxide.
- Author
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Pham HH and Wang LW
- Subjects
- Electric Conductivity, Electronics, Molecular Dynamics Simulation, Molecular Structure, Quantum Theory, Boron chemistry, Carbon chemistry, Fluorine chemistry, Nitrogen chemistry, Titanium chemistry
- Abstract
Although titanium dioxide (TiO2) has been extensively studied and widely used in energy and environmental areas, the amorphous form and its related defect properties are poorly understood. Recent studies, however, have emphasized the crucial role of amorphousness in producing competitively good performances in photochemical applications. In this work we have investigated for the first time the effects of various dopants (B, C, N and F) on charge carrier transport in amorphous titanium dioxide (a-TiO2), given that doping is a common technique used to tune the electronic properties of semiconductors, and that the existence of these impurities could also be unintentionally introduced during the synthesis process. The a-TiO2 model was obtained using a classical molecular dynamics method, followed by density-functional theory calculations (DFT + U, with Hubbard correction term U) on electronic structures and defect states. The formation of these impurity defects in a-TiO2 was found to be energetically more favorable by several eV than their crystal counterparts (in rutile). The contributions of these defect states to the charge transfer processes were examined by means of Marcus theory.
- Published
- 2015
- Full Text
- View/download PDF
24. Transition-metal-free C-H oxidative activation: persulfate-promoted selective benzylic mono- and difluorination.
- Author
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Ma JJ, Yi WB, Lu GP, and Cai C
- Subjects
- Catalysis, Fluorides chemistry, Gas Chromatography-Mass Spectrometry, Molecular Structure, Oxygen chemistry, Sulfates chemistry, Temperature, Carbon chemistry, Fluorine chemistry, Hydrogen chemistry, Metals chemistry, Transition Elements chemistry
- Abstract
An operationally simple and selective method for the direct conversion of benzylic C-H to C-F to obtain mono- and difluoromethylated arenes using Selectfluor™ as a fluorine source is developed. Persulfate can be used to selectively activate benzylic hydrogen atoms toward C-F bond formation without the aid of transition metal catalysts.
- Published
- 2015
- Full Text
- View/download PDF
25. Fluorine-decoupled carbon spectroscopy for the determination of configuration at fully substituted, trifluoromethyl- and perfluoroalkyl-bearing carbons: comparison with 19F-1H heteronuclear Overhauser effect spectroscopy.
- Author
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Mandhapati AR, Kato T, Matsushita T, Ksebati B, Vasella A, Böttger EC, and Crich D
- Subjects
- Crystallography, X-Ray, Fluorine chemistry, Magnetic Resonance Spectroscopy, Molecular Structure, Alkenes chemistry, Carbon chemistry, Fluorine Radioisotopes chemistry, Hydrocarbons, Fluorinated chemistry
- Abstract
The synthesis of a series of α-trifluoromethylcyclohexanols and analogous trimethylsilyl ethers by addition of the Ruppert-Prakash reagent to substituted cyclohexanones is presented. A method for the assignment of configuration of such compounds, of related α-trifluoromethylcyclohexylamines and of quaternary trifluoromethyl-substituted carbons is described based on the determination of the (3)J(CH) coupling constant between the fluorine-decoupled (13)CF3 resonance and the vicinal hydrogens. This method is dubbed fluorine-decoupled carbon spectroscopy and abbreviated FDCS. The method is also applied to the configurational assignment of substances bearing mono-, di-, and perfluoroalkyl rather than trifluoromethyl groups. The configuration of all substances was verified by either (19)F-(1)H heteronuclear Overhauser spectroscopy (HOESY) or X-ray crystallography. The relative merits of FDCS and HOESY are compared and contrasted. (2)J(CH), (3)J(CH), and (4)J(CH) coupling constants to (19)F decoupled CF3 groups in alkenes and arenes have also been determined and should prove to be useful in the structural assignment of trifluoromethylated alkenes and arenes.
- Published
- 2015
- Full Text
- View/download PDF
26. Reductive electropolymerization of a vinyl-containing poly-pyridyl complex on glassy carbon and fluorine-doped tin oxide electrodes.
- Author
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Harrison DP, Carpenter LS, and Hyde JT
- Subjects
- Electrochemical Techniques instrumentation, Electrodes, Oxidation-Reduction, Polymerization, Polymers chemical synthesis, Polymers chemistry, Pyrroles chemical synthesis, Carbon chemistry, Electrochemical Techniques methods, Fluorine chemistry, Pyrroles chemistry, Tin Compounds chemistry, Vinyl Compounds chemistry
- Abstract
Controllable electrode surface modification is important in a number of fields, especially those with solar fuels applications. Electropolymerization is one surface modification technique that electrodeposits a polymeric film at the surface of an electrode by utilizing an applied potential to initiate the polymerization of substrates in the Helmholtz layer. This useful technique was first established by a Murray-Meyer collaboration at the University of North Carolina at Chapel Hill in the early 1980s and utilized to study numerous physical phenomena of films containing inorganic complexes as the monomeric substrate. Here, we highlight a procedure for coating electrodes with an inorganic complex by performing reductive electropolymerization of the vinyl-containing poly-pyridyl complex onto glassy carbon and fluorine doped tin oxide coated electrodes. Recommendations on electrochemical cell configurations and troubleshooting procedures are included. Although not explicitly described here, oxidative electropolymerization of pyrrole-containing compounds follows similar procedures to vinyl-based reductive electropolymerization but are far less sensitive to oxygen and water.
- Published
- 2015
- Full Text
- View/download PDF
27. Understanding API-polymer proximities in amorphous stabilized composite drug products using fluorine-carbon 2D HETCOR solid-state NMR.
- Author
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Abraham A and Crull G
- Subjects
- Carbon chemistry, Fluorine chemistry, Magnetic Resonance Spectroscopy methods, Polymers chemistry
- Abstract
A simple and robust method for obtaining fluorine-carbon proximities was established using a (19)F-(13)C heteronuclear correlation (HETCOR) two-dimensional (2D) solid-state nuclear magnetic resonance (ssNMR) experiment under magic-angle spinning (MAS). The method was applied to study a crystalline active pharmaceutical ingredient (API), avagacestat, containing two types of fluorine atoms and its API-polymer composite drug product. These results provide insight into the molecular structure, aid with assigning the carbon resonances, and probe API-polymer proximities in amorphous spray dried dispersions (SDD). This method has an advantage over the commonly used (1)H-(13)C HETCOR because of the large chemical shift dispersion in the fluorine dimension. In the present study, fluorine-carbon distances up to 8 Å were probed, giving insight into the API structure, crystal packing, and assignments. Most importantly, the study demonstrates a method for probing an intimate molecular level contact between an amorphous API and a polymer in an SDD, giving insights into molecular association and understanding of the role of the polymer in API stability (such as recrystallization, degradation, etc.) in such novel composite drug products.
- Published
- 2014
- Full Text
- View/download PDF
28. The enhancing effects of group V σ-hole interactions on the F···O halogen bond.
- Author
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Li W, Zeng Y, Zhang X, Zheng S, and Meng L
- Subjects
- Static Electricity, Carbon chemistry, Fluorine chemistry, Nitrogen chemistry, Oxygen chemistry, Phosphorus chemistry
- Abstract
The σ-hole interaction, which occurs between the covalent IV-VII atoms and nucleophilic substances, has become a hot issue of weak interaction. In this work, NCF···O=PX3···(NCF)n (X = F, Cl, Br, H, CH3·; n = 0, 1, 2) complexes were constructed and studied based on the second-order Møller-Plesset perturbation theory (MP2) calculations to investigate the enhancing effects of group V σ-hole interactions on the F···O halogen bond. With increasing n, the FO halogen bond becomes stronger, indicating that the group V σ-hole interactions could enhance the F···O halogen bond. As the capacity of donating electrons of X increases, the most negative electrostatic potentials outside the oxygen atom of O=PX3···(NCF)n (n = 0, 1, 2) become more negative, resulting in a stronger F···O halogen bond. In the formation of a F···O halogen bond, along the sequence of X = F, Cl, Br, H, CH3 of the negative sites O=PX3, the electric field of the lone pair of oxygen becomes greater and causes a larger decrease in electron density outside the fluorine atom. On the other hand, with increasing n from 0 to 2, the group V σ-hole interactions also increase the electric field of lone pair of oxygen and results in a larger decrease in electron density outside the fluorine atom.
- Published
- 2014
- Full Text
- View/download PDF
29. Late-stage formation of carbon-fluorine bonds.
- Author
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Campbell MG and Ritter T
- Subjects
- Coordination Complexes chemical synthesis, Coordination Complexes chemistry, Fluorine Radioisotopes chemistry, Halogenation, Humans, Palladium chemistry, Positron-Emission Tomography, Radiopharmaceuticals chemical synthesis, Radiopharmaceuticals chemistry, Silver chemistry, Carbon chemistry, Fluorine chemistry
- Abstract
In this account, we review work from our lab on the development of methods for carbon-fluorine bond formation, with an emphasis on late-stage fluorination of functionalized small molecules and synthesis of (18) F-labeled molecules for potential use as tracers in positron emission tomography (PET). We attempt to highlight reactions that we feel are of particular practical relevance, as well as areas of research where there is still significant room for advancement., (Copyright © 2014 The Chemical Society of Japan and Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2014
- Full Text
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30. A convenient photocatalytic fluorination of unactivated C-H bonds.
- Author
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Halperin SD, Fan H, Chang S, Martin RE, and Britton R
- Subjects
- Catalysis, Positron-Emission Tomography, Carbon chemistry, Fluorine chemistry, Fluorine Radioisotopes chemistry, Halogenation, Hydrogen chemistry, Light, Sulfonamides chemistry
- Abstract
Fluorination reactions are essential to modern medicinal chemistry, thus providing a means to block site-selective metabolic degradation of drugs and access radiotracers for positron emission tomography imaging. Despite current sophistication in fluorination reagents and processes, the fluorination of unactivated CH bonds remains a significant challenge. Reported herein is a convenient and economic process for direct fluorination of unactivated CH bonds that exploits the hydrogen abstracting ability of a decatungstate photocatalyst in combination with the mild fluorine atom transfer reagent N-fluorobenzenesulfonimide. This operationally straightforward reaction provides direct access to a wide range of fluorinated organic molecules, including structurally complex natural products, acyl fluorides, and fluorinated amino acid derivatives., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2014
- Full Text
- View/download PDF
31. Preparation of fluorine-doped, carbon-encapsulated hollow Fe3O4 spheres as an efficient anode material for Li-ion batteries.
- Author
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Geng H, Zhou Q, Pan Y, Gu H, and Zheng J
- Subjects
- Electrochemical Techniques, Electrodes, Ions chemistry, Metal Nanoparticles chemistry, Polyvinyls chemistry, Carbon chemistry, Electric Power Supplies, Ferrosoferric Oxide chemistry, Fluorine chemistry, Lithium chemistry
- Abstract
Herein we report the design and synthesis of fluorine-doped, carbon-encapsulated hollow Fe3O4 spheres (h-Fe3O4@C/F) through mild heating of polyvinylidene fluoride (PVDF)-coated hollow Fe3O4 spheres. The spheres exhibit enhanced cyclic and rate performances. The as-prepared h-Fe3O4@C/F shows significantly improved electrochemical performance, with high reversible capacities of over 930 mA h g(-1) at a rate of 0.1 C after 70 cycles, 800 mA h g(-1) at a rate of 0.5 C after 120 cycles and 620 mA h g(-1) at a rate of 1 C after 200 cycles. This improved lithium storage performance is mainly ascribed to the encapsulation of the spheres with fluorine-doped carbon, which not only improves the reaction kinetics and stability of the solid electrolyte interface film but also prevents aggregation and drastic volume change of the Fe3O4 particles. These spheres thus represent a promising anode material in lithium-ion battery applications.
- Published
- 2014
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- View/download PDF
32. Modulating "jousting" C-F---H-C interactions with a bit of hydrogen bonding.
- Author
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Struble MD, Strull J, Patel K, Siegler MA, and Lectka T
- Subjects
- Quantum Theory, Carbon chemistry, Fluorine chemistry, Hydrogen Bonding
- Abstract
We have synthesized a series of molecules wherein very close C-F---H-C σ-bond interactions, which we have termed "jousting", can be perturbed through both red- and blue-shifted hydrogen bonding effects. These interactions were induced by the placement of various functional groups geminal to the H-C bond. "Jousting" interactions appear to be an admixture of F---H hydrogen bonding and C-H bond compression. The associated electronic effects from changes in the functional group at the X-position were also studied.
- Published
- 2014
- Full Text
- View/download PDF
33. Oxidative aliphatic C-H fluorination with manganese catalysts and fluoride ion.
- Author
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Liu W, Huang X, and Groves JT
- Subjects
- Catalysis, Gas Chromatography-Mass Spectrometry, Oxidation-Reduction, Carbon chemistry, Chemistry Techniques, Synthetic, Fluorine chemistry, Halogenation, Hydrogen chemistry, Manganese chemistry
- Abstract
Fluorination is a reaction that is useful in improving the chemical stability and changing the binding affinity of biologically active compounds. The protocol described here can be used to replace aliphatic, C(sp(3))-H hydrogen in small molecules with fluorine. Notably, isolated methylene groups and unactivated benzylic sites are accessible. The method uses readily available manganese porphyrin and manganese salen catalysts and various fluoride ion reagents, including silver fluoride (AgF), tetrabutylammonium fluoride and triethylamine trihydrofluoride (TREAT·HF), as the source of fluorine. Typically, the reactions afford 50-70% yield of mono-fluorinated products in one step. Two representative examples, the fragrance component celestolide and the nonsteroidal anti-inflammatory drug ibuprofen, are described; they produced useful isolated quantities (250-300 mg, ~50% yield) of fluorinated material over periods of 1-8 h. The procedures are performed in a typical fume hood using ordinary laboratory glassware. No special precautions to rigorously exclude water are required.
- Published
- 2013
- Full Text
- View/download PDF
34. Selective C-F bond activation: substitution of unactivated alkyl fluorides using YbI₃.
- Author
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Träff AM, Janjetovic M, Ta L, and Hilmersson G
- Subjects
- Fluorides chemistry, Lanthanoid Series Elements chemistry, Stereoisomerism, Carbon chemistry, Fluorine chemistry, Iodine chemistry, Ytterbium chemistry
- Published
- 2013
- Full Text
- View/download PDF
35. Asymmetric electrophilic fluorocyclization with carbon nucleophiles.
- Author
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Wolstenhulme JR, Rosenqvist J, Lozano O, Ilupeju J, Wurz N, Engle KM, Pidgeon GW, Moore PR, Sandford G, and Gouverneur V
- Subjects
- Crystallography, X-Ray, Cyclization, Metals chemistry, Molecular Conformation, Pyridinium Compounds chemistry, Stereoisomerism, Carbon chemistry, Fluorine chemistry
- Published
- 2013
- Full Text
- View/download PDF
36. Molecular tuning of the closed shell C-H···F-C hydrogen bond.
- Author
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Lu N, Ley RM, Cotton CE, Chung WC, Francisco JS, and Negishi E
- Subjects
- Hydrogen Bonding, Models, Chemical, Molecular Structure, Thermodynamics, Carbon chemistry, Electrons, Fluorine chemistry, Hydrogen chemistry
- Abstract
The existence of the rare six-membered and intramolecular C-H···F-C hydrogen-bond has been experimentally proven in the gas phase and in the solid state recently. However, the effect of the substituents on this C-H···F-C hydrogen-bond system has never been reported. In view of the importance of this type of C-H···F-C H-bonding whose weak interaction has been found critical in nanotechnology and biological systems, the nine functional groups composed of electron donating and electron withdrawing groups are inserted into this C-H···F-C interaction to study the group effect on the hydrogen bonding. Group effects on this C-H···F-C H-bonding system have been found, and their effects on the H-bonding system have been found to be tunable.
- Published
- 2013
- Full Text
- View/download PDF
37. C60/Bi2TiO4F2 heterojunction photocatalysts with enhanced visible-light activity for environmental remediation.
- Author
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Li G, Jiang B, Li X, Lian Z, Xiao S, Zhu J, Zhang D, and Li H
- Subjects
- Adsorption, Catalysis, Light, Photochemistry methods, Rhodamines analysis, Spectroscopy, Fourier Transform Infrared, Bismuth chemistry, Carbon chemistry, Environmental Restoration and Remediation methods, Fluorine chemistry, Fullerenes chemistry, Nanostructures chemistry, Oxides chemistry, Rhodamines isolation & purification, Titanium chemistry, Water Pollutants, Chemical chemistry, Water Purification methods
- Abstract
Fullerene (C60)-enhanced Bi2TiO4F2 hierarchical microspheres were prepared by a facile solvothermal method. Compared to the pure Bi2TiO4F2 photocatalyst, the C60/Bi2TiO4F2 samples exhibit much stronger photocatalytic performance for degrading Rhodamine B (RhB) and Eosin Y (EY) under visible light irradiation. Such greatly enhanced photocatalytic activity may be ascribed to strong combination and heterojunctions between C60 and Bi2TiO4F2, favorable for charge separation and light adsorption. Loading C60 on Bi2TiO4F2 results in a new photocatalytic mechanism (based on photo-generated hvb(+) and ·O2(-) radicals) different from that of pure Bi2TiO4F2.
- Published
- 2013
- Full Text
- View/download PDF
38. Fluorine detected 2D NMR experiments for the practical determination of size and sign of homonuclear F-F and heteronuclear C-F multiple bond J-coupling constants in multiple fluorinated compounds.
- Author
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Aspers RL, Ampt KA, Dvortsak P, Jaeger M, and Wijmenga SS
- Subjects
- Algorithms, Carbon analysis, Carbon chemistry, Fluorine analysis, Fluorine chemistry, Fluorine Compounds analysis, Fluorine Compounds chemistry, Nuclear Magnetic Resonance, Biomolecular methods
- Abstract
The use of fluorine in molecules obtained from chemical synthesis has become increasingly important within the pharmaceutical and agricultural industry. NMR characterization of these compounds is of great value with respect to their structure elucidation, their screening in metabolomics investigations and binding studies. The favorable NMR properties of the fluorine nucleus make NMR with fluorine detection of great value in this respect. A suite of NMR 2D F-F- and F-C-correlation experiments with fluorine detection was applied to the assignment of resonances, (n)J(CF)- and (n)J(FF)-couplings as well as the determination of their size and sign. The utilization of this experiment suite was exemplarily demonstrated for a highly fluorinated vinyl alkyl ether. Especially F-C HSQC and J-scaled F-C HMBC experiments allowed determining the size of the J-couplings of this compound. The relative sign of its homo- and heteronuclear couplings was achieved by different combinations of 2D NMR experiments, including non-selective and F2-selective F-C XLOC, F2-selective F-C HMQC, and F-F COSY. The F2-one/two-site selective F-C XLOC versions were found highly useful, as they led to simplifications of the common E.COSY patterns and resulted in a higher confidence level of the assignment by using selective excitation. The combination of F2-one/two-site selective F-C XLOC experiments with a F2-one-site selective F-C HMQC experiment provided the signs of all (n)J(CF)- and (n)J(FF)-couplings in the vinyl moiety of the test compound. Other combinations of experiments were found useful as well for special purposes when focusing for example on homonuclear couplings a combination of F-F COSY-10 with a F2-one-site selective F-C HMQC could be used. The E.COSY patterns in the spectra demonstrated were analyzed by use of the spin-selective displacement vectors, and in case of the XLOC also by use of the DQ- and ZQ-displacement vectors. The variety of experiments presented shall contribute to facilitate the interpretation of F-C correlations as well as to open alternative pathways for the determination of size and signs of homo- and heteronuclear couplings of multiply fluorinated small molecules., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
39. Noncatalytic pyridyl-directed alkylation and arylation carbon-fluorine bond of polyfluoroarenes with Grignard reagents.
- Author
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Xiong Y, Wu J, Xiao S, Xiao J, and Cao S
- Subjects
- Alkylation, Catalysis, Fluorobenzenes chemistry, Organometallic Compounds chemistry, Pyridines chemistry, Carbon chemistry, Fluorine chemistry, Fluorobenzenes chemical synthesis, Pyridines chemical synthesis
- Abstract
Cross-coupling reaction of polyfluoroarenes with Grignard reagents via pyridine-directed cleavage of C-F bond in the absence of metal catalysts was developed. A possible mechanism was suggested.
- Published
- 2013
- Full Text
- View/download PDF
40. Metal-free fluorination of C(sp3)-H bonds using a catalytic N-oxyl radical.
- Author
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Amaoka Y, Nagatomo M, and Inoue M
- Subjects
- Catalysis, Halogenation, Hydrogen Bonding, Molecular Structure, Carbon chemistry, Fluorine chemistry, Metals chemistry
- Abstract
A direct conversion of C(sp(3))-H bonds to C(sp(3))-F bonds has been developed. In this process, a catalytic N-oxyl radical generated from N,N-dihydroxypyromellitimide abstracts hydrogen from the C(sp(3))-H bond and Selectfluor acts to trap the resulting carbon radical to form the C(sp(3))-F bond. This simple metal-free protocol enables the chemoselective introduction of a fluorine atom into various aromatic and aliphatic compounds and serves as a powerful tool for the efficient synthesis of fluorinated molecules.
- Published
- 2013
- Full Text
- View/download PDF
41. Alkene trifluoromethylation coupled with C-C bond formation: construction of trifluoromethylated carbocycles and heterocycles.
- Author
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Egami H, Shimizu R, Kawamura S, and Sodeoka M
- Subjects
- Catalysis, Copper chemistry, Dioxanes chemistry, Fluorine chemistry, Alkenes chemistry, Carbon chemistry, Heterocyclic Compounds chemistry
- Published
- 2013
- Full Text
- View/download PDF
42. C(sp3)-F bond formation: a free-radical approach.
- Author
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Sibi MP and Landais Y
- Subjects
- Catalysis, Contrast Media chemical synthesis, Contrast Media chemistry, Halogenation, Manganese chemistry, Quantum Theory, Carbon chemistry, Fluorine chemistry, Free Radicals chemistry
- Published
- 2013
- Full Text
- View/download PDF
43. Enantioselective synthesis of epoxides having a tetrasubstituted trifluoromethylated carbon center: methylhydrazine-induced aerobic epoxidation of β,β-disubstituted enones.
- Author
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Kawai H, Okusu S, Yuan Z, Tokunaga E, Yamano A, Shiro M, and Shibata N
- Subjects
- Cyclic N-Oxides chemistry, Epoxy Compounds chemical synthesis, Molecular Structure, Oxygen chemistry, Stereoisomerism, Alkenes chemistry, Carbon chemistry, Epoxy Compounds chemistry, Fluorine chemistry, Monomethylhydrazine chemistry
- Published
- 2013
- Full Text
- View/download PDF
44. Anisotropy of chemical bonding in semifluorinated graphite C2F revealed with angle-resolved X-ray absorption spectroscopy.
- Author
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Okotrub AV, Yudanov NF, Asanov IP, Vyalikh DV, and Bulusheva LG
- Subjects
- Anisotropy, Binding Sites, Materials Testing, Nanostructures ultrastructure, Particle Size, Carbon chemistry, Fluorine chemistry, Graphite chemistry, Nanostructures chemistry, Spectrometry, X-Ray Emission methods
- Abstract
Highly oriented pyrolytic graphite characterized by a low misorientation of crystallites is fluorinated using a gaseous mixture of BrF(3) with Br(2) at room temperature. The golden-colored product, easily delaminating into micrometer-size transparent flakes, is an intercalation compound where Br(2) molecules are hosted between fluorinated graphene layers of approximate C(2)F composition. To unravel the chemical bonding in semifluorinated graphite, we apply angle-resolved near-edge X-ray absorption fine structure (NEXAFS) spectroscopy and quantum-chemical modeling. The strong angular dependence of the CK and FK edge NEXAFS spectra on the incident radiation indicates that room-temperature-produced graphite fluoride is a highly anisotropic material, where half of the carbon atoms are covalently bonded with fluorine, while the rest of the carbon atoms preserve π electrons. Comparison of the experimental CK edge spectrum with theoretical spectra plotted for C(2)F models reveals that fluorine atoms are more likely to form chains. This conclusion agrees with the atomic force microscopy observation of a chain-like pattern on the surface of graphite fluoride layers.
- Published
- 2013
- Full Text
- View/download PDF
45. Tuning efficiency of the 4-exo-trig cyclization by the electronic effect: ring closure of 3,3-difluoro-4-pentenyl carbon radicals and synthesis of a gem-difluorocyclobutane nucleoside.
- Author
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Kumamoto H, Kawahigashi S, Wakabayashi H, Nakano T, Miyaike T, Kitagawa Y, Abe H, Ito M, Haraguchi K, Balzarini J, Baba M, and Tanaka H
- Subjects
- Adenine chemical synthesis, Adenine chemistry, Alkenes chemistry, Butanes chemical synthesis, Cyclization, Free Radicals, Molecular Structure, Nucleosides chemical synthesis, Adenine analogs & derivatives, Butanes chemistry, Carbon chemistry, Fluorine chemistry, Nucleosides chemistry
- Abstract
4-exo-trig Cyclization reaction of a 4-pentenyl carbon radical containing the gem-difluoromethylene moiety adjacent to a radical accepting α,β-unsaturated ester was found to proceed efficiently to furnish a novel gem-difluorocyclobutane derivative. The cyclized product could be transformed into a gem-difluoromethylene analogue of oxetanocin T.
- Published
- 2012
- Full Text
- View/download PDF
46. A new entry to the construction of a quaternary carbon center having a fluorine atom--S(N)2' reaction of γ-fluoroallylic alcohol derivatives with various cyanocuprates.
- Author
-
Konno T, Ikemoto A, and Ishihara T
- Subjects
- Hydrocarbons, Fluorinated chemistry, Molecular Structure, Stereoisomerism, Carbon chemistry, Copper chemistry, Fluorine chemistry, Hydrocarbons, Fluorinated chemical synthesis, Organometallic Compounds chemistry, Propanols chemistry
- Abstract
Treatment of γ-fluoroallylic phosphate with various lower-ordered cyanocuprates derived from Grignard reagents, organolithium, and organozincs gave the corresponding S(N)2' products having a fluorine atom at a quaternary carbon center in excellent yields. This system could be successfully extended to the chiral version, enantiomerically pure fluorine-containing materials also being obtained in high yield.
- Published
- 2012
- Full Text
- View/download PDF
47. Proton transfer from C-6 of uridine 5'-monophosphate catalyzed by orotidine 5'-monophosphate decarboxylase: formation and stability of a vinyl carbanion intermediate and the effect of a 5-fluoro substituent.
- Author
-
Tsang WY, Wood BM, Wong FM, Wu W, Gerlt JA, Amyes TL, and Richard JP
- Subjects
- Humans, Models, Molecular, Orotidine-5'-Phosphate Decarboxylase chemistry, Protein Conformation, Saccharomyces cerevisiae enzymology, Alkenes chemistry, Biocatalysis, Carbon chemistry, Fluorine chemistry, Orotidine-5'-Phosphate Decarboxylase metabolism, Protons, Uridine Monophosphate chemistry
- Abstract
The exchange for deuterium of the C-6 protons of uridine 5'-monophosphate (UMP) and 5-fluorouridine 5'-monophosphate (F-UMP) catalyzed by yeast orotidine 5'-monophosphate decarboxylase (ScOMPDC) at pD 6.5-9.3 and 25 °C was monitored by (1)H NMR spectroscopy. Deuterium exchange proceeds by proton transfer from C-6 of the bound nucleotide to the deprotonated side chain of Lys-93 to give the enzyme-bound vinyl carbanion. The pD-rate profiles for k(cat) give turnover numbers for deuterium exchange into enzyme-bound UMP and F-UMP of 1.2 × 10(-5) and 0.041 s(-1), respectively, so that the 5-fluoro substituent results in a 3400-fold increase in the first-order rate constant for deuterium exchange. The binding of UMP and F-UMP to ScOMPDC results in 0.5 and 1.4 unit decreases, respectively, in the pK(a) of the side chain of the catalytic base Lys-93, showing that these nucleotides bind preferentially to the deprotonated enzyme. We also report the first carbon acid pK(a) values for proton transfer from C-6 of uridine (pK(CH) = 28.8) and 5-fluorouridine (pK(CH) = 25.1) in aqueous solution. The stabilizing effects of the 5-fluoro substituent on C-6 carbanion formation in solution (5 kcal/mol) and at ScOMPDC (6 kcal/mol) are similar. The binding of UMP and F-UMP to ScOMPDC results in a greater than 5 × 10(9)-fold increase in the equilibrium constant for proton transfer from C-6, so that ScOMPDC stabilizes the bound vinyl carbanions, relative to the bound nucleotides, by at least 13 kcal/mol. The pD-rate profile for k(cat)/K(m) for deuterium exchange into F-UMP gives the intrinsic second-order rate constant for exchange catalyzed by the deprotonated enzyme as 2300 M(-1) s(-1). This was used to calculate a total rate acceleration for ScOMPDC-catalyzed deuterium exchange of 3 × 10(10) M(-1), which corresponds to a transition-state stabilization for deuterium exchange of 14 kcal/mol. We conclude that a large portion of the total transition-state stabilization for the decarboxylation of orotidine 5'-monophosphate can be accounted for by stabilization of the enzyme-bound vinyl carbanion intermediate of the stepwise reaction.
- Published
- 2012
- Full Text
- View/download PDF
48. Unexpected geometrical effects on paramagnetic spin-orbit and spin-dipolar 2J(FF) couplings.
- Author
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Ducati LC, Contreras RH, and Tormena CF
- Subjects
- Reference Standards, Carbon chemistry, Fluorine chemistry, Magnetic Resonance Spectroscopy standards, Quantum Theory
- Abstract
The second-rank tensor character of the paramagnetic spin-orbit and spin-dipolar contributions to nuclear spin-spin coupling constants is usually ignored when NMR measurements are carried out in the isotropic phase. However, in this study it is shown that isotropic (2)J(FF) couplings strongly depend on the relative orientation of the C-F bonds containing the coupling nuclei and the eigenvectors of such tensors. Predictions about such effect are obtained using a qualitative approach based on the polarization propagator formalism at the RPA, and results are corroborated performing high-level ab initio spin-spin coupling calculations at the SOPPA(CCSD)/EPR-III//MP2/EPR-III level in a model system. It is highlighted that no calculations at the RPA level were carried out in this work. The quite promising results reported in this paper suggest that similar properties are expected to hold for the second-rank nuclear magnetic shielding tensor.
- Published
- 2012
- Full Text
- View/download PDF
49. Facile carbon-fluorine bond activation and subsequent functionalisation of 1,1-difluoroethylene and tetrafluoroethylene promoted by adjacent metal centres.
- Author
-
Slaney ME, Anderson DJ, Ristic-Petrovic D, McDonald R, and Cowie M
- Subjects
- Crystallography, X-Ray, Ligands, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Structure, Alkenes chemistry, Carbon chemistry, Fluorine chemistry, Fluorocarbons chemistry, Iridium chemistry, Metals chemistry, Organometallic Compounds chemistry, Vinyl Compounds chemistry
- Abstract
The bridging fluoroolefin ligands in the complexes [Ir(2)(CH(3))(CO)(2)(μ-olefin)(dppm)(2)][OTf] (olefin = tetrafluoroethylene, 1,1-difluoroethylene; dppm = μ-Ph(2)PCH(2)PPh(2); OTf(-) = CF(3)SO(3)(-)) are susceptible to facile fluoride ion abstraction. Both fluoroolefin complexes react with trimethylsilyltriflate (Me(3)SiOTf) to give the corresponding fluorovinyl products by abstraction of a single fluoride ion. Although the trifluorovinyl ligand is bound to one metal, the monofluorovinyl group is bridging, bound to one metal through carbon and to the other metal through a dative bond from fluorine. Addition of two equivalents of Me(3)SiOTf to the tetrafluoroethylene-bridged species gives the difluorovinylidene-bridged product [Ir(2)(CH(3))(OTf)(CO)(2)(μ-OTf)(μ-C=CF(2))(dppm)(2)][OTf]. The 1,1-difluoroethylene species is exceedingly reactive, reacting with water to give 2-fluoropropene and [Ir(2)(CO)(2)(μ-OH)(dppm)(2)][OTf] and with carbon monoxide to give [Ir(2)(CO)(3)(μ-κ(1):η(2)-C≡CCH(3))(dppm)(2)][OTf] together with two equivalents of HF. The trifluorovinyl product [Ir(2)(κ(1)-C(2)F(3))(OTf)(CO)(2)(μ-H)(μ-CH(2))(dppm)(2)][OTf], obtained through single C-F bond activation of the tetrafluoroethylene-bridged complex, reacts with H(2) to form trifluoroethylene, allowing the facile replacement of one fluorine in C(2)F(4) with hydrogen., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2012
- Full Text
- View/download PDF
50. Selective palladium-catalyzed C-F activation/carbon-carbon bond formation of polyfluoroaryl oxazolines.
- Author
-
Yu D, Shen Q, and Lu L
- Subjects
- Aldehydes chemistry, Boronic Acids chemistry, Catalysis, Esters chemistry, Ketones chemistry, Ligands, Magnetic Resonance Spectroscopy, Molecular Structure, Carbon chemistry, Fluorine chemistry, Hydrocarbons, Fluorinated chemical synthesis, Oxazoles chemical synthesis, Palladium chemistry
- Abstract
A selective palladium-catalyzed Suzuki-Miyaura coupling reaction of polyfluorophenyl oxazolines through ortho C-F activation is described. It was found that reactions with DPPF as the ligand occurred much faster than those with other ligands. A variety of arylboronic acids including challenging functionalized arylboronic acids such as enolizable ketones, aldehyde, cyano, ester, and trifluoromethyl groups were tolerated with the reaction conditions.
- Published
- 2012
- Full Text
- View/download PDF
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