Introduction Of Fluorine Research Articles

Influence of fluorination on CO2adsorption in materials derived from fluorinated covalent triazine framework precursors

Give me more fluorines: introduction of fluorine in the structure of Covalent Triazine Frameworks can improve their CO2adsorption. Materials with optimal fluorine content and narrow nanopore distribution are promising CO2scavengers.

The influence of fluorine doping on transport properties in the novel proton conductors Ba4In2Zr2O11-0.5xFx with perovskite structure

The effect of fluorine doping on the transport properties of perovskite-related complex oxides based on oxygen-ion conductor Ba4In2Zr2O11 is analyzed. The effect of fluorine doping and air humidity on the cell volume is established. The introduction of fluorine into the oxygen sublattice leads to the decreasing in the cell volume. The hydration of samples leads to the lattice expansion for both undoped and doped samples in comparison with unhydrated samples. The amount of water uptake decreases with the increase in the fluorine concentration. It was shown that fluorine doping allows to increase the proton conductivity in the region of low fluorine concentrations. The determining factor is not the change in the concentration of the current carrier, but the increase in its mobility.

18 F-Labeled Derivatives of Irbesartan for Angiotensin II Receptor PET Imaging.

The renin angiotensin aldosterone system (RAAS) is a hormonal cascade involved in the regulation of blood pressure and electrolyte balance, and represents a common target for the treatment of various diseases including hypertension, heart failure, and diabetes. Herein we present a novel 18 F-labeled derivative of the drug irbesartan, one of the most prescribed angiotensin II type 1 receptor (AT1 R) antagonists, for in vivo positron emission tomography (PET). This allows the in vivo measurement of AT1 R expression, and thus the evaluation of functional changes in its expression under pathophysiological conditions. We followed various synthetic approaches optimized for the introduction of fluorine into different positions of the aliphatic side chain of irbesartan. Radioligand binding studies revealed that fluorine atoms at specified positions (α-position (IC50 =6.6 nm) and δ-position (IC50 =8.5 nm) of the aliphatic side chain) do not alter the binding properties of irbesartan (IC50 =1.6 nm). After successful radiolabeling with fluorine-18 in a radiochemical yield of 11 %, we observed high renal uptake in healthy rats and pigs, which could be decreased by pretreatment with the parent compound irbesartan.

Therapeutic use of fluorinated nucleosides - progress in patents.

Fluorinated nucleosides constitute a large class of chemotherapeutics approved for clinical use. The pharmacokinetic and pharmacodynamic properties of a drug can be affected, as a consequence of modulation of electronic, lipophilic and steric parameters, by the introduction of fluorine into the structure of drug-like molecule. Herein, we focus on fluorinated-nucleoside analogs, their therapeutic use and applications based on the patent literature from 2014 to 2018. We briefly discuss the clinical properties of anticancer and antiviral fluorine-containing nucleos(t)ides US FDA-approved or in development, and highlight their resistance mechanisms and limitations in the clinic. We emphasize patent inventions related to improved synthetic methods toward selected nucleos(t)ide analogs including the phosphoramidate sofosbuvir and 18F-labeled nucleosides FLT and FMAU, used as a 18F-PET tracers.

Antibacterial ability, cytocompatibility and hemocompatibility of fluorinated graphene

Graphene halides are promising two-dimensional systems which have interesting physical and chemical properties. In particular, high quality fluorinated graphene offers a great potential in modulating variable properties by regulating its surface microstructure. Moreover, the fluorine introduction and carbon-fluorine bonding characters will enable some interesting biological response. Here, the biological responses to bacteria and cells of fluorinated graphene were studied. Present work revealed that partially fluorinated graphene behaved satisfactory antibacterial ability. Fluorinated graphene showed well facilitating function to cell adhesion in early period, however, after a longer incubation period, the enhanced intracellular ROS level in rBMSCs on the fully fluorinated graphene gives rise to the decrease of cell viability. It was found that there is no statistical difference in the activity of alkaline phosphatase (ALP) and matrix mineralization of rBMSCs on pristine graphene, partially fluorinated graphene and fluorographene. In addition, the introduction of fluorine into pristine graphene plane reduced the adhesion and aggregation of blood platelets due to the attenuation of π-π interaction between material surface and blood protein. The findings in this work revealed that partial fluorinated graphene exhibited better antibacterial ability and cytocompatibility, outperforming pristine graphene and fluorographene.

Selective C(sp3)−H and C(sp2)−H Fluorination of Alcohols Using Practical Auxiliaries

AbstractSelective introduction of fluorine into molecules by the cleavage of inert C−H bonds is of central academic and synthetic interest, yet remains challenging. Given the central role of alcohols in organic chemistry as the most ubiquitous building blocks, a versatile and selective C(sp3)−H and C(sp2)−H fluorination of simple alcohols, enabled by novel designed exo‐directing groups, is described. C(sp2)−H bond fluorination was achieved by using a simple acetone oxime as auxiliary, whereas a new, modular and easily accessible bidentate auxiliary was developed for the efficient and site‐selective fluorination of various primary methyl, methylene, and benzylic C(sp3)−H bonds. Fluorinated alcohols can readily be accessed by the removal of auxiliaries, and significantly expands the synthetic prospect of the present procedure.

Selective C(sp3)−H and C(sp2)−H Fluorination of Alcohols Using Practical Auxiliaries

Selective introduction of fluorine into molecules by the cleavage of inert C-H bonds is of central academic and synthetic interest, yet remains challenging. Given the central role of alcohols in organic chemistry as the most ubiquitous building blocks, a versatile and selective C(sp3 )-H and C(sp2 )-H fluorination of simple alcohols, enabled by novel designed exo-directing groups, is described. C(sp2 )-H bond fluorination was achieved by using a simple acetone oxime as auxiliary, whereas a new, modular and easily accessible bidentate auxiliary was developed for the efficient and site-selective fluorination of various primary methyl, methylene, and benzylic C(sp3 )-H bonds. Fluorinated alcohols can readily be accessed by the removal of auxiliaries, and significantly expands the synthetic prospect of the present procedure.

Synthesis, Structural Characterization, and Antiangiogenic Activity of Polyfluorinated Benzamides.

The introduction of fluorine into bioactive molecules is a matter of importance in medicinal chemistry. In this study, representatives of various chemical entities of fluoroaromatic compounds were synthesized. Depending on the reaction conditions, either tetrafluorophthalimides or ammonium tetrafluorophthalamates are accessible from tetrafluorophthalic anhydride and primary amines. Tetrafluorophthalamic acids undergo thermal decarboxylation to yield tetrafluorobenzamides. These could be successfully converted upon treatment with primary amines, in the course of an aromatic nucleophilic substitution, to 2,3,5-trifluorobenzamides with respective amino substituents at the 4-position. The five structure types were characterized by means of spectroscopic and crystallographic methods. The synthesized compounds were evaluated as inhibitors of angiogenesis by measuring microvessel outgrowth in a rat aortic ring assay. The biological activity was maintained throughout these different polyfluorinated chemotypes.

Preparation and characterization of a self‐catalyzed fluorinated novolac‐phthalonitrile resin

A self‐catalyzed fluorinated novolac‐phthalonitrile resin was synthesized by nucleophilic substitution reaction between fluorinated novolac oligomer and 4‐nitrophthalonitrile. Structure of the final product was characterized by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance. With the introduction of fluorine into the backbone, the fluorinated novolac‐phthalonitrile presented elevated performance. Compared with the analogous novolac‐phthalonitrile resin, the dielectric constant of the cured fluorinated resin decreased from 3.30 to 3.15, and the dielectric loss effectively decreased from 0.012 to 0.004 at the frequency of 1 MHz. Furthermore, the fluorinated novolac‐phthalonitrile resin possessed a broader processing window and higher thermo‐oxidative stability than the analogous novolac‐phthalonitrile resin. Consequently, the fluorinated novolac‐phthalonitrile resin may be a good candidate for matrix of high performance composite in electronic and aerospace industries.

The Introduction of Fluorine and Sulfur Atoms into Benzotriazole‐Based p‐Type Polymers to Match with a Benzotriazole‐Containing n‐Type Small Molecule: “The Same‐Acceptor‐Strategy” to Realize High Open‐Circuit Voltage

Abstract“The Same‐Acceptor‐Strategy” (SAS) adopts benzotriazole (BTA)‐based p‐type polymers paired with a new BTA based non‐fullerene acceptor BTA13 to minimize the trade‐off between the open‐circuit voltage (VOC) and short circuit current (JSC). The fluorination and sulfuration are introduced to lower the highest occupied molecular orbitals (HOMO) of the polymers. The fluorinated polymer of J52‐F shows the higher power conversion efficiency (PCE) of 8.36% than the analog polymer of J52, benefited from a good balance between an improved VOC of 1.18 V and a JSC of 11.55 mA cm−2. Further adding alkylthio groups on J52‐F, the resulted polymer, J52‐FS, exhibits the highest VOC of 1.24 V with a decreased energy loss of 0.48 eV, compared with 0.67 eV for J52 and 0.54 eV for J52‐F. However, J52‐FS shows an inferior PCE (3.84%) with a lower JSC of 6.74 mA cm−2, because the small ΔEHOMO between J52‐FS and BTA13 (0.02 eV) gives rise to the inefficient hole transfer and high charge recombination, as well as low carrier mobilities. The results of this study clearly demonstrate that the introduction of different atoms in p‐type polymers is effective to improve the SAS and realize the high (VOC) and PCE.

Fine‐Tuning the Proteolytic Stability of Peptides with Fluorinated Amino Acids

The decoration of organic compounds with fluorine substituents is a strategy well‐known to medicinal chemists. Around 25 % of drugs on the market contain at least one fluorine atom, as fluorine's unique properties very often produce effects that cannot be achieved by any other known functional group. The changes in molecular properties due to the incorporation of fluorine most relevant to medicinal chemistry are conformation, pKa values of neighboring functional groups, and interaction with proteins and membranes. The introduction of fluorine dramatically impacts these and in turn the pharmacokinetics and biological half‐lives of not only small molecules but peptides, which show high binding affinity and selectivity for their target and are, therefore, also desirable lead compounds in drug development. Unfortunately, several factors can limit the efficacy of peptides and biologicals including low bioavailability and protease digestion. Although the literature has numerous examples showing that fluorine can improve the latter aspect, there are also cases to the contrary. This review aims to provide an overview of the influence of fluorinated amino acids on the proteolytic stability of peptides.

Adjusting the Structure of 2'-Modified Nucleosides and Oligonucleotides via C4'-α-F or C4'-α-OMe Substitution: Synthesis and Conformational Analysis.

We report the first syntheses of three nucleoside analogues, namely, 2',4'-diOMe-rU, 2'-OMe,4'-F-rU, and 2'-F,4'-OMe-araU, via stereoselective introduction of fluorine or methoxy functionalities at the C4'-α-position of a 4',5'-olefinic intermediate. Conformational analyses of these nucleosides and comparison to other previously reported 2',4'-disubstituted nucleoside analogues make it possible to evaluate the effect of fluorine and methoxy substitution on the sugar pucker, as assessed by NMR, X-ray diffraction, and computational methods. We found that C4'-α-F/OMe substituents reinforce the C3'-endo ( north) conformation of 2'-OMe-rU. Furthermore, the predominant C2'-endo ( south/ east) conformation of 2'-F-araU switches to C3'-endo upon introduction of these substituents at C4'. The nucleoside analogues were incorporated into DNA and RNA oligonucleotides via standard phosphoramidite chemistry, and their effects on the thermal stability of homo- and heteroduplexes were assessed via UV thermal melting experiments. We found that 4'-substituents can modulate the binding affinity of the parent 2'-modified oligomers, inducing a mildly destabilizing or stabilizing effect depending on the duplex type. This study expands the spectrum of oligonucleotide modifications available for rational design of oligonucleotide therapeutics.

Structure-activity relationship of uridine-based nucleoside phosphoramidate prodrugs for inhibition of dengue virus RNA-dependent RNA polymerase

To identify a potent and selective nucleoside inhibitor of dengue virus RNA-dependent RNA polymerase, a series of 2′- and/or 4′-ribose sugar modified uridine nucleoside phosphoramidate prodrugs and their corresponding triphosphates were synthesized and evaluated. Replacement of 2′-OH with 2′-F led to be a poor substrate for both dengue virus and human mitochondrial RNA polymerases. Instead of 2′-fluorination, the introduction of fluorine at the ribose 4′-position was found not to affect the inhibition of the dengue virus polymerase with a reduction in uptake by mitochondrial RNA polymerase. 2′-C-ethynyl-4′-F-uridine phosphoramidate prodrug displayed potent anti-dengue virus activity in the primary human peripheral blood mononuclear cell-based assay with no significant cytotoxicity in human hepatocellular liver carcinoma cell lines and no mitochondrial toxicity in the cell-based assay using human prostate cancer cell lines.

Highly flattened donor-acceptor polymers based on fluoride-substituent acceptors for efficient heterojunction solar cells

For high performance polymer solar cells, the effects of planarity and alkyl chain steric hindrance are systematically examined in the polymer poly[1-(4-(4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)-6-methylbenzo[1,2-b:4,5-b′]dithiophen-2-yl)-6-methylthieno[3,4-b]thiophen-2-yl)-2-ethylhexan-1-one] (P4) constructed with a benzo[1,2-b:4,5-b′] dithiophene (BDT) plane with symmetrical thiophene side chains, poly[2-ethyl-1-(6-methyl-4-(6-methyl-4,4-dioctyl-4H-silolo[3,2-b:4,5-b′]dithiophen-2-yl)thieno[3,4-b]thiophen-2-yl)hexan-1-one] (P5), composed of silaindacenodithiophene, poly[2-ethyl-1- (6-methyl-4-(6-methyl-4-octyl-4H-dithieno[3,2-b:2′,3′-d]pyrrol-2-yl)thieno[3,4-b]thiophen-2-yl)hexan-1-one] (P6), based on pyrrole moieties and the corresponding F-containing polymers, poly[1-(4-(4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)-6-methylbenzo[1,2-b:4,5-b′]dithiophen-2-yl)-3-fluoro-6-methylthieno[3,4-b]thiophen-2-yl)-2-ethylhexan-1-one] (P1), Poly[2-ethyl-1-(3-fluoro-6-methyl-4-(6-methyl-4,4-dioctyl-4H-silolo[3,2-b:4,5-b′]dithiophen-2-yl)thieno[3,4-b]thiophen-2-yl)hexan-1-one] (P2), and Poly[2-ethyl-1-(3-fluoro-6-methyl-4-(6-methyl-4-octyl-4H-dithieno[3,2-b:2′,3′-d]pyrrol-2-yl)thieno[3,4-b]thiophen-2-yl)hexan-1-one] (P3). Except for P1 and P4, the alkyl chain is directly linked to the main chain in the polymers. P1 has a high degree of flatness because flanking thienyls can decrease the torsion angle between conjugated units. In addition, the introduction of fluorine (F) on the thienothiophene acceptors of P4 reduces the dihedral angle between the BDT and thienothiophene, resulting in a more planar P1. Moreover, the introduction of short alkyl and thiophene side chains minimizes the intermolecular steric hindrance of P1 and ensures strong inter-chain aggregation and π-π stacking. However, the introduction of F in P2 and P3 increases the dihedral angle relative to non-F-containing P5 and P6. Finally, an efficiency of 7.1% is obtained for P1, leading to a 50% increase in power conversion efficiency (PCE) compared with P4. This work is a step towards enhanced polymer planarity and minimal intermolecular steric hindrance for the development of efficient polymer heterojunction solar cells.

UV light induced electrophilic fluorination of graphene oxide

The introduction of fluorine into graphene endows it with unusual physical and chemical properties. Developing a valid and safe fluorinating method and advancing the fundamental understanding of fluorination mechanism are highly anticipated. Here, a photochemical route for synthesizing fluorinated graphene oxide via one-step ultraviolet (UV) irradiation using F-TEDA-BF4 (Selectfluor) as fluorinating reagent is reported. The results suggest that, unlike the general view, the oxygenic groups are not contributed to the reactivity of graphene. An electrophilic fluorination mechanism including UV induced electronic excitation and single electron transfer process is put forward.

The short-range structure and hydration process of fluorine-substituted double perovskites based on barium-calcium niobate Ba2CaNbO5.5

In this work the influence of fluorine substitution on the structure and hydration processes of solid solutions Ba2-0.5xCaNbO5.5-xFx and Ba2CaNbO5.5-0.5yFy with different concentration of oxygen vacancies was investigated. It was found that fluorine substitution leads to the decrease in the cell volume due to the decrease in niobium-oxygen bond length. The possibility of water uptake was proved, the introduction of fluorine leads to decrease in concentration of protons and to increase in hydrogen bonds.

Late-stage fluorination of bridged scaffolds: Chemoselective generation of a CHF group at three positions of the bicyclo[3.3.1]nonane system

Monofluorobicyclo[3.3.1]nonane derivatives were prepared by late-stage fluorination, often proceeding with control of stereochemistry. Introduction of fluorine at the 3-, 6- or 7-position was achieved chemoselectively, the bicyclo system being constructed by a tandem one-pot Michael-aldol annulation. The major conformer was deduced for each of the fluorobicyclo compounds prepared, each possessing a unique CF orientation on a common rigid bridged scaffold that can be polysubstituted.

Structures and photophysical performances of (fluoro)salicylate stabilized polyoxo-titanium clusters

The introduction of fluorine in salicylic acid yielded different polyoxo-titanium clusters with distinct photophysical properties.

The first lead fluorooxoborate PbB5O8F: achieving the coexistence of large birefringence and deep-ultraviolet cut-off edge.

Herein, the first lead fluorooxoborate PbB5O8F has been structurally designed following a strategy of fluorine introduction into borates. PbB5O8F presents the first case of possessing the [B5O10F]6- fundamental building block. More importantly, PbB5O8F fully achieves the coexistence of large birefringence and deep-ultraviolet cut-off edge. This short cut-off edge sets a new record among lead borates.

Fluorinated Electrolytes for Li-Ion Batteries: The Lithium Difluoro(oxalato)borate Additive for Stabilizing the Solid Electrolyte Interphase.

Fluorinated electrolytes based on fluoroethylene carbonate (FEC) have been considered as promising alternative electrolytes for high-voltage and high-energy capacity lithium-ion batteries (LIBs). However, the compatibility of the fluorinated electrolytes with graphite negative electrodes is unclear. In this paper, we have systematically investigated, for the first time, the stability of fluorinated electrolytes with graphite negative electrodes, and the result shows that unlike the ethylene carbonate (EC)-based electrolyte, the FEC-based electrolyte (EC was totally replaced by FEC) is incapable of forming a protective and effective solid electrolyte interphase (SEI) that protects the electrolyte from runaway reduction on the graphite surface. The reason is that the lowest unoccupied molecular orbital energy levels are also lowered by the introduction of fluorine into the solvent, and the FEC solvent has poorer resistance against reduction, leading to instability on the graphite negative electrode. To tackle this problem, two lithium salts of lithium bis(oxalato)borate and lithium difluoro(oxalato)borate (LiDFOB) have been investigated as negative-electrode film-forming additives. Incorporation of only 0.5 wt % LiDFOB to a FEC-based electrolyte [1.0 M LiPF6 in 3:7 (FEC–ethyl methyl carbonate)] results in excellent cycling performance of the graphite negative electrode. This improved property originates from the generation of a thinner and better quality SEI film with little LiF by the sacrificial reduction of the LiDFOB additive on the graphite negative electrode surface. On the other hand, this additive can stabilize the electrolyte by scavenging HF. Meanwhile, the incorporated LiDFOB additive has positive influence on the interphase layer on the positive electrode surface and significantly decreases the amount of HF formation, finally leading to improved cycling stability and rate capability of LiNi0.5Mn1.5O4 electrodes at a high cutoff voltage of 5 V. The data demonstrate that the LiDFOB additive not only exhibits a superior compatibility with graphite but also improves the electrochemical properties of high-voltage spinel LiNi0.5Mn1.5O4 positive electrodes considerably, confirming its potential as a prospective, multifunctional additive for 5 V fluorinated electrolytes in high-energy capacity lithium-ion batteries (LIBs).