Fluorine Substituents Research Articles

Gold Difluorocarbenoid Complexes: Spectroscopic and Chemical Profiling

AbstractGold carbenes of the general type [LAu=CR2]+ are sufficiently long‐lived for spectroscopic inspection only if the substituents compensate for the largely missing stabilization of the carbene center by the [LAu]+ fragment. π‐Donation by two fluorine substituents (R=F) is insufficient; rather, difluorocarbene complexes are so deprived in electron density that they sequester even “weakly coordinating” anions such as triflate or triflimide. This particular bonding situation translates into unmistakable carbenium ion chemistry upon reaction with stilbene as a model substrate.

Gold Difluorocarbenoid Complexes: Spectroscopic and Chemical Profiling.

Gold carbenes of the general type [LAu=CR2 ]+ are sufficiently long-lived for spectroscopic inspection only if the substituents compensate for the largely missing stabilization of the carbene center by the [LAu]+ fragment. π-Donation by two fluorine substituents (R=F) is insufficient; rather, difluorocarbene complexes are so deprived in electron density that they sequester even "weakly coordinating" anions such as triflate or triflimide. This particular bonding situation translates into unmistakable carbenium ion chemistry upon reaction with stilbene as a model substrate.

Binding propterties of two Ru(II) polypyridyl complexes containing dppz units and fluorine groups with poly(U)·poly(A) ∗ poly(U) triplex

In this work, two Ru(II)-dppz (dppz = dipyrido[3,2-a:2′,3′-c]phenazine) complexes containing fluorine substituents, [Ru(bpy)2(7-F-dppz)]2+ (Ru1, bpy = 2,2′-bipyridine, 7-F-dppz = 7-fluorodipyrido[3,2-a:2′,3′-c]phenazine) and [Ru(phen)2(7-F-dppz)]2+ (Ru2, phen = 1,10-phenanthroline), have been synthesized and characterized. Binding properties of Ru1 and Ru2 with the RNA poly(U)·poly(A) ∗ poly(U) triplex have been studied by spectroscopic methods and viscosity measurements. The obtained results indicate that the binding differences of the two complexes with the triplex may be attributed to the ancillary ligand effects, implying that the better planarity and greater hydrophobicity of ancillary ligands are advantageous to the π–π stacking interaction between Ru2 and the triplex, thus Ru2 stabilizes the triplex strongly than Ru1. Denaturation of the triplex shows that both Ru1 and Ru2 can not only highly stabilize the template duplex of the triplex, but also significantly stabilize the third strand. Compared with the triplex stabilizing effects for the reported Ru(II)-dppz complexes, thermal melting experiments suggest that the fluorine substituent on the ligand dppz can probably decrease electrostatic repulsion between the three strands of the triplex, thereby Ru1 and Ru2 significantly increase the triplex stabilization. Results obtained from this work further confirm that the substituent electron effect of dppz-based ligands and the planarity and hydrophobicity of ancillary ligands play an important role in the triplex stabilizing effects by Ru(II)-dppz complexes.

Low-bandgap non-fullerene acceptors based on selenophene π spacer and alkylated indaceno[1,2-b:5,6-b′]dithiophene for organic solar cells

Three non-fullerene acceptors, i.e. IDT2SeC2C4, IDT2SeC2C42F and IDT2SeC2C44F, with selenophene π bridge between central alkylated indaceno[1,2-b:5,6-b′]dithiophene (IDT) unit and terminal 1,1-dicyanomethylene-3-indanones (ICs) with 0–2 fluorine substituents were synthesized. These molecules presented low optical band gaps in the range of 1.30–1.44 eV. Moreover, compared with the counterparts with phenyl side chains on IDT unit, the alkyl-based molecules achieved higher electron mobility owing to the more ordered and closer π-π stacking. Organic solar cells (OSCs) based on the non-fullerene acceptors were fabricated with the wide band gap polymer PBDB-T as donor. Attributed to the desired morphology with more obvious fibril-like structures, the devices based on IDT2SeC2C42F and IDT2SeC2C44F with fluorinated IC terminals delivered high power conversion efficiencies (PCEs) over 10%, whereas the devices based on DT2SeC2C4 showed a lower PCE of 8.92%.

Structural modification of indomethacin toward selective inhibition of COX-2 with a significant increase in van der Waals contributions.

We have synthesized a fluorinated analogue of indomethacin bearing a 3,3,3-trifluoroprop-1-enyl group at its 2-position and evaluated its inhibitory activity towards the COX-1 and COX-2 enzymes in vitro. The results revealed that this fluorinated analogue exhibited much greater inhibitory activity and selectivity towards COX-2 than indomethacin. The increased affinity between the fluorinated analogue and COX-2 was attributed to a significant increase in van der Waals contacts (i.e. van der Waals contributions in ΔG were -13.80 kcal/mol for COX-1 and -18.46 kcal/mol for COX-2), explaining an effect of the fluorine substituent in enzyme selectivity. This newly synthesized fluorinated analogue therefore represents a potent and selective COX-2 inhibitor.

Breaking π–π Interactions in Carboxylic Acid Monolayers on Rutile TiO2(110) Leads to Unexpected Long-Range Ordering

Carboxylic acids are ubiquitous building blocks in supramolecular and surface chemistry because of their strong but reversible binding to metal cations. In these applications, the relative ordering and orientation of the acids can affect performance. We present a rational approach to tuning intermolecular interactions with the goal of maintaining a favorable molecular conformation while also enabling long-range ordering. In particular, we show that scanning tunneling microscopy (STM) images of m- or p-fluorobenzoate monolayers on rutile (110) produced in aqueous solutions display very large (2 × 1) grains without the intermolecular pairing observed in similarly prepared benzoate monolayers. The lack of pairing is attributed to the electronegative fluorine substituent, which reduces π–π or quadrupolar interactions between the phenyl groups on the adjacent molecules and stabilizes a favorable configuration between the aromatic head group and the carboxylate-binding moiety. In spite of the reduced interactio...

Next generation QTAIM for the design of quinone-based switches

Abstract Investigation of the hydrogen transfer tautomerization process yielded metallic hydrogen bonds in the benzoquinone-like core of the switch. Bond-path framework sets B and Bσ, comprising a three-stranded, non-minimal 3-D bond, which included the familiar QTAIM bond-path and two additional paths defining the least and most preferred directions of electron density motion, were used with QTAIM and the stress-tensor respectively. The B and Bσ were visualized and uncovered the destabilizing effects on the hydrogen bond of the presence of an Fe atom. The lengths of B and Bσ quantified this effect and the dependence on the position of a fluorine substituent.

Tetracoordinate Boron-Fused Double [5]Helicenes as Cathode Active Materials for Lithium Batteries.

Double [5]helicenes possessing two tetracoordinated boron atoms at the ring junctions were synthesized from glycine anhydride in three steps. The helicene with fluorine substituents on the boron atoms was employed as a cathode active material in a lithium battery to demonstrate moderate performance in the 1.8-3.5 V range with more than 63 mAh g-1 discharge capacity for 20 cycles and high Coulombic efficiency of over 90%.

The formation of all-cis-(multi)fluorinated piperidines by a dearomatization-hydrogenation process.

Piperidines and fluorine substituents are both independently indispensable components in pharmaceuticals, agrochemicals and materials. Logically, the incorporation of fluorine atoms into piperidine scaffolds is therefore an area of tremendous potential. However, synthetic approaches towards the formation of these architectures are often impractical. The diastereoselective synthesis of substituted monofluorinated piperidines often requires substrates with pre-defined stereochemistry. That of multifluorinated piperidines is even more challenging, and often needs to be carried out in multistep syntheses. In this report, we describe a straightforward process for the one-pot rhodium-catalysed dearomatization-hydrogenation of fluoropyridine precursors. This strategy enables the formation of a plethora of substituted all-cis-(multi)fluorinated piperidines in a highly diastereoselective fashion through pyridine dearomatization followed by complete saturation of the resulting intermediates by hydrogenation. Fluorinated piperidines with defined axial/equatorial orientation of fluorine substituents were successfully applied in the preparation of commercial drugs analogues. Additionally, fluorinated PipPhos as well as fluorinated ionic liquids were obtained by this dearomatization-hydrogenation process.

Fluorinated Organic Electro‐Optic Quinolinium Crystals for THz Wave Generation

AbstractFluorinated electro‐optic crystals with state‐of‐the‐art second‐order nonlinear optical response and excellent characteristics for terahertz (THz) wave generation are reported. The fluorinated organic ionic crystals consist of optically highly nonlinear fluorinated HM6FQ (6‐fluoro‐2‐(4‐hydroxy‐3‐methoxystyryl)‐1‐methylquinolinium) or HM7FQ (7‐fluoro‐2‐(4‐hydroxy‐3‐methoxystyryl)‐1‐methylquinolinium) cations and 4‐methylbenzenesulfonate (T) counter anions. Compared to benchmark electro‐optic crystals based on nonfluorinated HMQ (2‐(4‐hydroxy‐3‐methoxystyryl)‐1‐methylquinolinium) cations, introducing fluorine substituent on HM6FQ cations creates additional hydrogen bonds (ArF···HC). Such a molecular engineering leads to an enhanced thermal stability and significant modulations of phonon vibrational modes of crystals in THz frequency region, while excellent π–π stacking and space filling characteristics of HM6FQ cations in crystals lead to state‐of‐the‐art diagonal component of the macroscopic nonlinear optical susceptibility, similar to the case of HMQ cations. HM6FQ‐based crystals exhibit a very high optical‐to‐THz conversion efficiency, comparable to benchmark HMQ‐based crystals. In addition, due to additional hydrogen bonds induced by fluorine substituents, the spectral shape of the generated THz wave is remarkably modified; e.g., the largest spectral gap is near 1.5 and 2.0 THz for HM6FQ‐ and HMQ‐based crystals, respectively. The fluorinated cationic engineering on nonlinear optical crystals having benchmark nonlinear optical response is, as far as is known, reported for the first time.

Germanium Fluoride Nanocages as Optically Transparent n-Type Materials and Their Endohedral Metallofullerene Derivatives.

Carbon- and silicon-based n-type materials tend to suffer from instability of the corresponding radical anions. With DFT calculations, we explore a promising route to overcome such challenges with molecular nanocages which utilize the heavier element Ge. The addition of fluorine substituents creates large electron affinities in the range 2.5-5.5 eV and HOMO-LUMO gaps between 1.6 and 3.2 eV. The LUMOs envelop the surfaces of these structures, suggesting extensive delocalization of injected electrons, analogous to fullerene acceptors. Moreover, these Ge nF n inorganic cages are found to be transparent in the UV-visible region as probed with their excited states. Their capacitance, linear polarizabilities, and dielectric constants are computed and found to be on the same order of magnitude as saturated oligomers and some extended π-organics (azobenzenes). Furthermore, we explore fullerene-type endohedral isomers, i.e., cages with internal substituents or guest atoms, and find them to be more stable than the parent exohedral isomers by up to -206.45 kcal mol-1. We also consider the addition of Li, He, Cs, and Bi, to probe the utility of the exo/ endo cages as host-guest systems. The endohedral He/Li@F8@Ge60F52 cages are significantly more stable than their parent exohedral isomers He/Li@Ge60F52 by -182.46 and -49.22 kcal mol-1, respectively. The energy of formation of endohedral He@F8@Ge60F52 is exothermic by -10.4 kcal mol-1, while Cs and Bi guests are too large to be accommodated but are stable in the exohedral parent cages. Conceivable applications of these materials include n-type semiconductors and transparent electrodes, with potential for novel energy storage modalities.

Novel fluorinated quaternary ammonium salts and their in vitro activity as trypanocidal agents

As the impact of aromatic rings and fluorine substituents in commercial drugs is attributed to their electronic distribution and structure rigidity that determine metabolic stability and toxicity, 30 quaternary ammonium salts (QAS) of the form [X-CH2N(CH3)2(CH2)nCH = C(Ar2)]+I− (where X=H, Cl or I, n = 2 or 3, and Ar = m-C6H4CF3, p-C6H4CF3, m-C6H4F, p-C6H4F or C6H5) were tested as potential trypanocidal agents and assessed their cytotoxicity on U-937 cells. CF3-substituted QASs exhibited LC50 values in the range of 0.5 to 6.4 μg/mL and trypanocidal EC50 values between 0.6 and 7.0 μg/mL, while the LC50 values for F-substituted analogs are between 7.0 and 207 μg/mL and EC50 values range from 3.8 to 40.9 μg/mL. As a general trend, the more effective are those bearing an N-iodomethyl moiety or having a longer tether, and para-substituted ones. Few drugs therapies are in use for Chagas disease, so this study becomes a promising contribution.

Fluorine substituted methoxyphenylalkyl amides as potent melatonin receptor agonists.

A series of fluorine substituted methoxyphenylalkyl amides were prepared with different orientations of the fluorine and methoxy groups with respect to the alkylamide side chain and with alkyl sides of differing lengths (n = 1-3). β-Dimethyl and α-methyl derivatives were also synthesised. The compounds were tested as melatonin agonists and antagonists using the pigment aggregation of Xenopus melanophores as the biological assay. A number of these compounds were potent melatonin agonists, the potency depending on the length of the alkyl chain, the orientation of the methoxy and fluorine substituents, the amide chain length and, for the ethyl side-chain analogues, the presence of β-substituents.

Strategic modification of ligands for remarkable piezochromic luminescence (PCL) based on a neutral Ir(iii) phosphor

A neutral Ir(iii) complex has been synthesized by introducing a carboxyl group and fluorine substituents into the ligands to construct a new piezochromic luminescence (PCL) active material.

Novel carbazole-based donor-isoindolo[2,1-a]benzimidazol-11-one acceptor polymers for ternary flash memory and light-emission.

Three novel donor–acceptor polymers (PCz0, PCz2 and PCz4) based on 9-(9-heptadecanyl)-9H-carbazole and isoindolo[2,1-a]benzimidazol-11-one with fluorine substituents (0, 2 and 4) on the acceptor unit were prepared by Suzuki polymerization. The synthesized polymers were studied by theoretical calculation, and optical and electrochemical characterizations to further investigate the performance of memory storage and light-emission. The memory devices of the three polymers all exhibited obvious ternary flash behavior with total ON/OFF state current ratio around 104 and threshold voltages below 3.0 V, with no other blending or doping. Bright emissions of an electroluminescence device based on PCz0 was obtained at 556 nm, the maximum brightness was 2006 cd m−2 with EQE of 0.21%. The results suggested that polymers with the structure of carbazole-based donor as backbone and isoindolo[2,1-a]benzimidazol-11-one segment as acceptor could be excellent materials for memory storage and light-emitting applications with further investigation and could be used for further design of other new polymer systems.

Влияние фторзаместителей на параметры внутри- и межмолекулярного взаимодействия молекул 1,4-дистирилбензола

A comparative analysis of the parameters of the Franсk-Kondon and Herzberg-Teller interactions forming the fine-structure spectra of α, ω-tetrafluorodysterylbenzene, 1,4-distyrylbenzene and stilbene is carried out. It is shown that the introduction of fluorine substituents leads to reduce the dipole moment of the molecule, and as a result, reduces the values of the parameters of intermolecular interaction. It is concluded that the parameters of intra- and intermolecular interactions, forming the fine-structure spectra of the selected molecules, make it possible to use the fragmentary approach in the description of fundamental bands.

Macrocyclic pentamers functionalised around their periphery as potential building blocks.

The elaboration of a five-fold symmetric macrocyclic aromatic pentamer bearing peripheral benzyloxy and hydroxyl groups is described. These could be used to explore further functionalisation for use as pentagonal building blocks. The internal fluorine-substituted macrocycle has been prepared via a one-pot procedure which is an improvement on the stepwise chain growth approach reported in the literature.

Synthesis, structure and NMR study of fluorinated isoxazoles derived from hemi-curcuminoids

The purpose of this work is to prepare a series of isoxazoles bearing phenyl and 4'-hydroxy-styryl substituents at position 3 and 5; besides the phenyl group of the styryl residue bears one or two fluorine substituents. They were prepared to study their structure in the solid state and in solution by X-ray crystallography and solid-state NMR (SSNMR) for the solid state and NMR for the solution. The reaction of hydroxylamine with hemi-curcuminoid β-diketones affords two isomeric isoxazoles we have named series a (3-phenyl) and b (5-phenyl) that have been identified and characterized. Four pairs have been prepared that in three cases bear one or two fluorine atoms. Three X-ray structures have been determined 3a, 3b and 5b; 3a crystallizes without solvent, 3b crystallizes with a water molecule hydrogen-bonded to a phenolic OH, finally 5b crystallizes as a solvate with a methanol molecule hydrogen-bonded to the isoxazole N atom. This hydrogen bond results in larger differences between 15N chemical shifts in DMSO-d6 solution and in the solid state. The splitting of some signals observed in Cross-Polarization Magic Angle Spinning (CPMAS) 13C NMR was assigned to 1JCF dipolar couplings. The combined use of crystallography and SSNMR affords a complete characterization of isomeric isoxazoles, in particular the assignment of an isoxazole to a or to b series is not a trivial matter. In this work, we describe methods for the synthesis of isoxazoles bearing fluorine substituents that are promising structures for drug discovery.

Synthesis, characterization and self-assembly of pyridyl-appended Gemini-shaped hexabenzocoronene amphiphiles

Four different Gemini-shaped hexa-peri-hexabenzocoronenes (HBCs) 1–4, carrying pyridyl-appended side chains were synthesized, and their self-assembling behaviors were investigated. Compared with HBCs 1 and 2, four electron-withdrawing fluorine substituents at the periphery of the HBC core were introduced in HBCs 3 and 4. HBCs 2 and 4 have longer hydrophilic chains than those of HBCs 1 and 3. The self-assembly behaviors of amphiphilic HBCs 1–4 in different conditions were investigated, the results revealed that HBCs 1, 2 and 3 self-assembled into nanotubes, HBC 4 self-assembled into nanofibers.

Synthesis and mesomorphic properties of the nematic mesophase benzoxazole derivatives with big twist angle of difluoro-biphenyl unit

ABSTRACTModifying the position and numbers of lateral fluorine substituent is a common method to design and adjust the mesophase of liquid crystal compounds. Here, a series of 2-(2,2ʹ-difluoro-4ʹ-alkoxy-1,1ʹ-biphenyl-4-yl)-5-substituted benzoxazole with both non-polar (H, CH3) and polar (NO2) groups (coded as nPF(2)PF(2)Bx) is synthesised and characterised. All of the compounds show a conspicuous inter-ring twist angle of 38° compared with corresponding reference compounds I and II which are calculated by density functional theory method, and it is interesting to note that the final compounds nPF(2)PF(2)Bx show only nematic mesophase during heating or cooling. Meanwhile, the UV-vis absorption bands and photoluminescence emission peaks both display remarkable blue-shifted. The aforementioned results reveal that lateral difluoro substituents play a key role to stable the nematic mesophase by increasing the dihedral angle of biphenyl.