Fluorine Substituents Research Articles

Skeletal Transformation Triggered by C-F Bond Activation after Photochemical Rearrangement of Fluorinated [7]Helicenes.

Tri- and tetra-fluorinated [7]helicenes are photolabile and undergo a double fluorine atom transfer. Herein, we show that the transferred product further undergoes a skeletal transformation on silica gel. The transformation begins with activation of the allylic C-F bond on the silanol surface. Then, the resulting carbocation readily undergoes a regioselective nucleophilic aromatic substitution with water, depending on the position of the fluorine substituents. Hexafluoro-2-propanol also activated the allylic C-F bond and acted as a nucleophile. These findings support the generation of a highly reactive cationic electrophilic intermediate in the successive transformations involving fluorine atoms.

Effect of fluorine substituents on photovoltaic properties of D–a type conjugated polymers with quinoxaline unit

Two quinoxaline-based polymers were synthesized to investigate the effect of electron-withdrawing fluorine substituents on the photovoltaic properties of the polymers. In order to prepare the reference quinoxaline-based D-A type polymer PBS-T-Q, the electron-donating benzodithiophene derivative and electron-accepting 2,3-dithenylquinoxaline moiety were polymerized under the Stille condition. Thereafter, the strong electron-withdrawing fluorine atom was incorporated into the 6-position of the 2,3-dithenylquinoxaline unit of the reference polymer to yield the additional target polymer PBS-T-QF. The photovoltaic properties of the two polymers were examined by manufacturing an inverted-type device the photovoltaic properties of the quinoxaline-based polymers were enhanced by the addition of a fluorine substituent.

Fluorinated Phosphoadenosine 5'-Phosphosulfate Analogues for Continuous Sulfotransferase Activity Monitoring and Inhibitor Screening by 19F NMR Spectroscopy.

Sulfotransferases (STs) are ubiquitous enzymes that participate in a vast number of biological processes involving sulfuryl group (SO3) transfer. 3′-phosphoadenosine 5′-phosphosulfate (PAPS) is the universal ST cofactor, serving as the “active sulfate” source in cells. Herein, we report the synthesis of three fluorinated PAPS analogues that bear fluorine or trifluoromethyl substituents at the C2 or C8 positions of adenine and their evaluation as substitute cofactors that enable ST activity to be quantified and real-time-monitored by fluorine-19 nuclear magnetic resonance (19F NMR) spectroscopy. Using plant AtSOT18 and human SULT1A3 as two model enzymes, we reveal that the fluorinated PAPS analogues show complementary properties with regard to recognition by enzymes and the working 19F NMR pH range and are attractive versatile tools for studying STs. Finally, we developed an 19F NMR assay for screening potential inhibitors against SULT1A3, thereby highlighting the possible use of fluorinated PAPS analogues for the discovery of drugs for ST-related diseases.

Diarylation of N- and O-nucleophiles through a metal-free cascade reaction

Diarylation of N- and O-nucleophiles through a metal-free cascade reaction

The pH dependence and role of fluorinated substituent of enoxacin binding to ferrihydrite

The sorption of antibiotics on iron (hydr)oxides is an important process that influences their environmental fate. Ferrihydrite (Fh) nanosized iron hydroxide is omnipresent in nature. However, the sorption mechanism of fluoroquinolone (FQ) antibiotics on Fh is unclear. Here, a combined experimental and computational study was conducted to investigate the sorption of enoxacin (ENO) as one model of FQs on Fh. Pipemidic acid (PPA), as a structural analog of ENO, was selected to compare the effect of fluorinated substituent on the sorption mechanism. Results indicated that the average Kd values of ENO at pH = 7.0 and 8.0 were 1.72 and 2.75 times higher than those at pH in the ranges of 4.0–6.0 and 9.0–10.0, respectively. The main sorption mechanisms included electrostatic, hydrophobic interaction, and inner-sphere complexation. The fluorinated substituent of ENO facilitated its sorption on Fh through enhancing its hydrophobicity as well as modifying its dissociation constants and charge distribution. The findings give new insights into the significant influence of active fluorinated substituents on the environmental behaviors of fluorinated pharmaceuticals.

Molecular fluorinated cobalt phthalocyanine immobilized on ordered mesoporous carbon as an electrochemical sensing platform for sensitive detection of hydrogen peroxide and hydrazine in alkaline medium

• Molecular CoPcF16 is anchored on CMK-3. • The interaction between CoPcF16 and CMK-3 is investigated. • CMK-3-CoPcF16 exhibits high electrocatalytic activity. • Sensitive detection of H 2 O 2 and hydrazine is achieved. Non-precious molecular cobalt phthalocyanine (CoPc) complexes have been considered to be promising electrocatalysts due to diversity of substituents and carbon supporting matrixes. Here, we report a highly dispersed fluorinated CoPc (CoPcF16) molecule electrocatalyst immobilized in ordered mesoporous carbon CMK-3 (CMK-3-CoPcF16) via π-π interaction. The molecular electrocatalyst is characterized by X-ray photoelectron spectroscopy, Raman spectrum, electronic paramagnetic resonance, scanning electron microscopy, transmission electron microscopy and electrochemical impedance spectroscopy. The combination of fluorine substituents and high loading capability of CMK-3 increase the solubility of CoPc, suppress aggregation, and thereby enhance the electrocatalytic performance. As a result, the CMK-3-CoPcF16 modified electrode shows high electrocatalytic activity towards the oxidation of hydrogen peroxide and hydrazine. CMK-3-CoPcF16 hybrid is successfully presented as an electrochemical sensing platform for sensitive detection of H 2 O 2 and hydrazine with a detection limit of 0.03 and 0.2 µM, respectively.

Fluoro-nitrogen Cations.

The crystal structures of [NH3 F]+ [CF3 SO3 ]- , [NH2 F2 ]+ [SbF6 ]- , and [N2 F3 ]+ [Sb3 F16 ]- have been determined, representing the first structural characterizations of these simple fluoro-nitrogen cations. The influences of the hybridization of the central nitrogen atom and of the number of fluorine substituents on the N-F bond lengths are evaluated for the series N2 F+ , N2 F3 + , NF2 O+ , NH3 F+ , NH2 F2 + , and NF4 + . It is shown that the N-F bond length decreases from 1.40 Å to 1.26 Å with increasing fluorine substitution and increasing s-character of the nitrogen atom, and that unusual N-F bond lengths reported in the previous literature are caused by disorder problems.

Fluoro‐nitrogen Cations

AbstractThe crystal structures of [NH3F]+[CF3SO3]−, [NH2F2]+[SbF6]−, and [N2F3]+[Sb3F16]− have been determined, representing the first structural characterizations of these simple fluoro‐nitrogen cations. The influences of the hybridization of the central nitrogen atom and of the number of fluorine substituents on the N−F bond lengths are evaluated for the series N2F+, N2F3+, NF2O+, NH3F+, NH2F2+, and NF4+. It is shown that the N−F bond length decreases from 1.40 Å to 1.26 Å with increasing fluorine substitution and increasing s‐character of the nitrogen atom, and that unusual N−F bond lengths reported in the previous literature are caused by disorder problems

The effect of fluorine substituents on the crystal structure and spin crossover behavior of the cation [MnIII(3,5-diHal-sal2323)]+ complex family with BPh4 anions

The effect of fluorine substituents on the structure and magnetic behavior of [Mn(R′,R′′-sal2323)]BPh4 complexes was studied and compared it with that of chlorine and bromine substituents.

The effect of a lateral alkyloxy chain on the ferroelectric nematic phase.

The synthesis and characterisation of two series of low molar mass liquid crystals, the 4-[(4-nitrophenoxy)carbonyl]phenyl 2-alkoxy-4-methoxybenzoates (series 5-m) and the 4-[(3-fluoro-4-nitrophenoxy)carbonyl]phenyl 2-alkoxy-4-methoxybenzoates (series 6-m) are reported in order to explore the effects of a lateral alkyloxy chain on the formation and stability of the recently discovered ferroelectric nematic phase. In both series m, the number of carbon atoms in the lateral chain, is varied from one to nine. The two series differ by the addition of a fluorine substituent in the 6-m series. 5-1 is the extensively studied ferroelectric nematogen RM734. All the members of the 5-m series exhibited both a conventional nematic, N, and ferroelectric nematic, NF, phase, whereas all the members of the 6-m series exhibit a direct NF-I transition with the exception of 6-1 that also exhibits a N phase. The replacement of a hydrogen atom by a fluorine atom reduces the nematic-isotropic transition temperature, T NI, whereas the ferroelectric nematic-nematic, or isotropic, transition temperature, T NFN/I, increases. This is interpreted in terms of the reduced structural anisotropy associated with the larger fluorine atom whereas the increase in the stability of the NF phase reflects changes in polarity and polarizability. The dependence of T NI and T NFN/I on m in both series is similar, and these initially decrease on increasing m but converge to limiting values on further increasing m. This suggests that the lateral alkyloxy chain may adopt conformations in which it lies along the major axis of the mesogenic unit.

Novel polychromogenic fluorine-substituted spiropyrans demonstrating either uni- or bidirectional photochromism as multipurpose molecular switches

Novel photochromic spiropyrans (SPPs) of the indoline series with fluorine substituents and cationic fragments or formyl groups at positions 6′ and 8′ of the 2H-chromene moiety were synthesized using a simple one-pot method. Molecular structures of 8′-fluorine-substituted compounds were refined by single-crystal X-ray, which revealed that both SPPs exist in their merocyanine forms in a crystalline state. It was established, that structure-related photochromic transformations of studied SPPs include: positive photochromism for SPPs with a vinyl-3H-indolium fragment or a formyl group at position 8′ of the benzopyran moiety; negative photochromism for SPP with a vinyl-3H-indolium fragment at position 6′ of the molecule; both positive and negative photochromism for SPP with a formyl group in position 6′ of the molecule, demonstrating the properties of photochromic “balance”. The polychromogenicity of the obtained compounds allows them to be considered as fluorescent molecular switches and bipolar absorption switches.

Recent Innovations of Organo-fluorine Synthesis and Pharmacokinetics

The fluorinated compounds have significance in medicinal chemistry and pharmaceutical research. The introduction of fluorine atom in the heterocyclic compounds increases biological activity by favourable physiochemical interactions. The combination of heterocycles with fluorine substituents has a wide range of applications in the study of various pharmacological research. The compounds not only exhibit biological activity but have also shown unique physical and chemical characteristics features that open the new avenues for multidisciplinary research. Fluorine atom tolerance to maximal functional groups, simplicity in operation, replacing hydrogen with fluorine of bioactive molecules are more efficient for the synthesis of fluorinated compounds at the commercial level. The fluorine substitution also increases the binding affinity to the targeted protein. Furthermore, the incorporation of fluorine on the drug molecules helps in enhancing the polarity, increasing the rate of drug metabolism and improving metabolic stability. The pharmacokinetic study plays an important role in clinical research. In 1996, researcher Whitford found that the pharmacokinetics of fluorine is affected by pH and quantity in the bone study. The pH of organofluoride influences fluoride absorption, distribution, and excretion. It also increases the stability when bound to carbon atom, resulting in increased bioactivity. This is the primary reason that fluoride is a key component of around 25% of currently available active drugs for various diseases, including cancer, diabetes, HIV etc. Not only the pharmacokinetic properties but also the physical properties of the drug can be enhanced or altered by selective insertion at the key place of the fluorine atom in the drug candidate. In this report, we have studied and referred to the interesting research articles reported since 2000 for the synthesis of low fluorine substituted organic compounds for medicinal research and pharmacokinetic use, example neurological diseases, cancer, and tuberculosis research.

Effect of electron-withdrawing fluorine and cyano substituents on photovoltaic properties of two-dimensional quinoxaline-based polymers

In this study, strong electron-withdrawing fluorine (F) and cyano (CN) substituents are selectively incorporated into the quinoxaline unit of two-dimensional (2D) D–A-type polymers to investigate their effects on the photovoltaic properties of the polymers. To construct the 2D polymeric structure, electron-donating benzodithiophene and methoxy-substituted triphenylamine are directly linked to the horizontal and vertical directions of the quinoxaline acceptor, respectively. After analyzing the structural, optical, and electrochemical properties of the resultant F- and CN-substituted polymers, labeled as PBCl-MTQF and PBCl-MTQCN, respectively, inverted-type polymer solar cells with a non-fullerene Y6 acceptor are fabricated to investigate the photovoltaic performances of the polymers. It is discovered that the maximum power conversion efficiency of PBCl-MTQF is 7.48%, whereas that of PBCl-MTQCN is limited to 3.52%. This significantly reduced PCE of the device based on PBCl-MTQCN is ascribed to the formation of irregular, large aggregates in the active layer, which can readily aggravate the charge recombination and charge transport kinetics of the device. Therefore, the photovoltaic performance of 2D quinoxaline-based D–A-type polymers is significantly affected by the type of electron-withdrawing substituent.

Electrochemical O-trifluoromethylation of electron-deficient phenols

A simple and sustainable one-step strategy for the preparation of electron-deficient aryl trifluoromethyl ethers (ArOCF3) from the corresponding phenols by electrochemical synthesis is presented. Anodic oxidation of trifluoromethane sulfinate (Langlois reagent) leads to direct O-trifluoromethylation of phenol-derivatives bearing fluorine, chlorine, bromine and nitrile substituents under mild conditions in yields up to 75% and in gram-scale. This electrochemical protocol provides an economic and green synthesis for an otherwise inaccessible class of molecules without the need for expensive or toxic reagents, oxidants or metal catalysts.

Two‐Dimensional Fluorinated Covalent Organic Frameworks with Tunable Hydrophobicity for Ultrafast Oil–Water Separation

AbstractCovalent organic frameworks (COFs) hold great potentials for addressing the challenge of highly efficient oil–water separation, but they are restricted by the poor wettability and processability as crystalline membranes. Here we report the design and synthesis of two‐dimensional (2D) robust COFs with controllable hydrophobicity and processability, allowing the COF layers to be directly grown on the support surfaces. Three 2D COFs with AA or ABC stacking are prepared by condensation of triamines with fluorine and/or isopropyl groups and perfluorodialdehyde. They all show excellent tolerance to water, acid, and base, with water contact angles (CA) of 111.5–145.8°. The two COFs with isopropyl and fluorine mixtures can grow as a coating on a stainless‐steel net (SSN) substrate, whereas the one with only fluorine substituents cannot. The superhydrophobic COF@SSN coating with water CA of up to 150.1° displays high water‐resistance and self‐cleaning properties, enabling high oil–water separation performances with an efficiency of over 99.5 % and a permeation flux of 2.84×105 L m−2 h−1, which are among the highest values reported for state‐of‐the‐art membranes.

Two-Dimensional Fluorinated Covalent Organic Frameworks with Tunable Hydrophobicity for Ultrafast Oil-Water Separation.

Covalent organic frameworks (COFs) hold great potentials for addressing the challenge of highly efficient oil-water separation, but they are restricted by the poor wettability and processability as crystalline membranes. Here we report the design and synthesis of two-dimensional (2D) robust COFs with controllable hydrophobicity and processability, allowing the COF layers to be directly grown on the support surfaces. Three 2D COFs with AA or ABC stacking are prepared by condensation of triamines with fluorine and/or isopropyl groups and perfluorodialdehyde. They all show excellent tolerance to water, acid, and base, with water contact angles (CA) of 111.5-145.8°. The two COFs with isopropyl and fluorine mixtures can grow as a coating on a stainless-steel net (SSN) substrate, whereas the one with only fluorine substituents cannot. The superhydrophobic COF@SSN coating with water CA of up to 150.1° displays high water-resistance and self-cleaning properties, enabling high oil-water separation performances with an efficiency of over 99.5 % and a permeation flux of 2.84×105 L m-2 h-1 , which are among the highest values reported for state-of-the-art membranes.

Fluoromaticity: The Molecular Orbital Contributions of Fluorine Substituents to the π-Systems of Aromatic Rings.

The addition of fluorine atoms to an aromatic ring brings about an additional set of π-bonding and antibonding orbitals culminating after the addition of the sixth fluorine with a new set of π-aromatic-like orbitals that affect the molecule in a way that we will refer to hereafter as “fluoromaticity”. Depending on the number and position of the fluorine atoms, the contributed π-orbitals can even further stabilize the ring leading to smaller bond lengths within the ring and higher resistance to addition reactions. This added ring stability partially explains the high thermostability and chemical resistance found in polymers containing fluorinated aromatics in their architecture. A similar molecular orbital effect is seen with the addition of other halogen atoms to aromatic rings, though to a much smaller degree and not resulting in the additional ring stability.

Photodegradation of norfloxacin in ice: Role of the fluorine substituent

Ice is an important medium in cold regions, because it regulates the environmental behaviors and the fate of pollutants. The photodegradation of fluoroquinolone (FQ) antibiotics as emerging contaminants of concern in ice remains poorly understood. Here, the photodegradation of fluorine-containing norfloxacin (NOR) as one model of FQs in ice formed from freezing solutions was investigated. Pipemidic acid (PPA) as a structural analogue of NOR was selected to compare the effect of molecular structure on the antibiotic photodegradation in the ice. Results suggested that the photodegradation rate constant of NOR in ice relative to pure water increased by 40.0%. Both the absorbance in the absorption spectra and quantum yields of NOR in ice over water increased by 1.4 times. Direct photodegradation mainly caused the defluorination of NOR, which was more important than cleavage and oxidation of the piperazine ring by self-sensitized photooxidation in ice. The defluorination rate of NOR in the ice relative to water increased by about 12.7%. The fluorine substituent played a more important role in the NOR photodegradation in the ice, resulting in a 1.6-fold increase in the photodegradation rate constant of NOR relative to PPA. This work provides a new insight into the role of fluorine substituents in the photodegradation of fluorinated pharmaceuticals in cold regions.

The driving factors of per- and polyfluorinated alkyl substance (PFAS) accumulation in selected fish species: The influence of position in river continuum, fish feed composition, and pollutant properties

Per- and polyfluorinated alkyl substances (PFASs) represent a group of highly recalcitrant micropollutants, that continuously endanger the environment. The present work describes the geographical trends of fish contamination by individual PFASs (including new compounds, e.g., Gen-X) assessed by analyzing the muscle tissues of 5 separate freshwater fish species from 10 locations on the Czech section of the Elbe River and its largest tributary, the Vltava River. The data of this study also showed that the majority of the detected PFASs consisted of long-chain representatives (perfluorooctane sulfonate (PFOS), perfluorononanoic acid, perfluorodecanoic acid, and perfluoroundecanoic acid), whereas short-chain PFASs as well as other compounds such as Gen-X were detected in relatively small quantities. The maximum concentrations of the targeted 32 PFASs in fish were detected in the lower stretches of the Vltava and Elbe Rivers, reaching 289.9 ng/g dw, 140.5 ng/g dw, and 162.7 ng/g dw for chub, roach, and nase, respectively. Moreover, the relationships between the PFAS (PFOS) concentrations in fish muscle tissue and isotopic ratios (δ15N and δ13C) were studied to understand the effect of feed composition and position in the river continuum as a proxy for anthropogenic activity. Redundancy analysis and variation partitioning showed that the largest part of the data variability was explained by the interaction of position in the river continuum and δ15N (δ13C) of the fish. The PFAS concentrations increased downstream and were positively correlated with δ15N and negatively correlated with δ13C. A detailed study at one location also demonstrated the significant relationship between δ15N (estimated trophic position) and PFASs (PFOS) concentrations. From the tested physicochemical properties, the molecular mass and number of fluorine substituents seem to play crucial roles in PFAS bioaccumulation.

Optical and static dielectric properties of two nematogenic isothiocyanato-tolane compounds: a comparative study

The optical and dielectric properties of two laterally monofluorinated isothiocyanato-tolane nematogens, which differ only on the position of fluorine atom in the core, have been studied as a function of temperature. A four-parameter model is validated by fitting the experimentally measured values of refractive indices, birefringence and average refractive indices of the compounds with the theoretical ones. The position of fluorine substituent in the rigid core have been found to have little effect on optical birefringence, but pronounced effect on dielectric anisotropy.