Additional Fluorine Research Articles

Dark conglomerate phases of azobenzene derived bent-core mesogens - relationships between the molecular structure and mirror symmetry breaking in soft matter.

New 4-bromoresorcinol based bent-core molecules with peripheral fluoro substituted azobenzene wings have been synthesized and the liquid crystalline self-assembly was investigated by differential scanning calorimetry (DSC), optical polarizing microscopy (POM), electro-optic studies and X-ray diffraction (XRD). A new type of optically isotropic mesophase composed of chiral domains with opposite handedness (dark conglomerate phases, DC phases) is observed, which for some homologues with medium alkyl chain length is stable down to ambient temperature. It is proposed that these DC phases are formed by helical twisted nano-domains of limited size and composed of the crystallized aromatic cores which are separated by the disordered alkyl chains. This structure is distinct from the previously known soft helical nano-filament phases (HNF phases, B4 phases) formed by extended crystalline nano-filaments and also distinct from the fluid sponge phases composed of deformed fluid layers. Comparison with related bent-core molecules having H, F, Cl, I, CH3 and CN groups in the 4-position at the resorcinol core, either with or without additional peripheral fluorines, provided information about the effects of these substituents on the tendency to form DC phases. Based on these relationships and by comparison with the minimum energy conformations obtained by DFT calculations a hypothesis is provided for the formation of DC phases depending on the molecular structure.

Influence of fluorination on UV spectra of polyurethane structural fragments

Results of TDDFT calculations of the characteristics for excited singlet states of fluorinated urethanes containing from one to six fluorine atoms were presented. The influence of the number and location of the fluorine atoms in the urethane structure on the formation of its UV absorption spectrum was analyzed. It was established that fluorination of a phenyl group in the ortho-positions led to steric hindrance in the urethane structure and to rotation of the urethane group by a significant angle (of about 20°). The rotation angle of the urethane group could reach 60° and more with additional fluorination of the amine. Such changes in the urethane structure were accompanied by characteristic significant bathochromic shifts of the long-wavelength absorption bands.

Economic Surface Treatment of Ti-Alloys to Improve their Resistance against Environmental High Temperature Attack

High temperature Ti-alloys are usually sophisticated and hence expensive. To allow the use of cheaper alloys at elevated temperatures an economic and easy to apply procedure was developed to improve their high temperature capability. The treatment consists of a combination of Al-enrichment in a shallow surface region plus additional fluorination. The Al-enrichment at elevated temperatures leads to the formation of intermetallic TiAl-phases. These phases improve the oxidation resistance of Ti-alloys but not to a sufficient extent. An additional fluorine treatment of the Al-enriched surface leads to the formation of a protective alumina scale due to the fluorine effect. In this paper results from high temperature exposure tests performed on different Ti-alloys without any treatment and with a combination of Al-treatment plus fluorination are presented. The results are discussed in the view of the use of the optimized Ti-components for several high temperature applications.

An insight into coordination ability of dicyanoimidazolato anions toward lithium in presence of acetonitrile. Crystal structures of novel lithium battery electrolyte salts

New generation of imidazole-derived salts was characterized by single-crystal X-ray diffraction experiments for the first time. Herein, we present crystal structures of lithium salts containing original 4,5-dicyanoimidazolato anions substituted with trifluoromethyl, pentafluoroethyl and heptafluoropropyl groups. Studied compounds crystallize as acetonitrile-solvated dimers with four-coordinate lithium cations. Structures of crystalline materials were examined with regard to the fine properties of electrolyte providing valuable information about coordination ability of substituted 4,5-dicyanoimidazolato anions. Anions act as ditopic N donor ligands containing additional weak fluorine donor-centers. Donor nitrogen atoms of imidazole and cyano groups, show slightly lower basicity than electroneutral acetonitrile solvent molecules coordinated to lithium. Presence of bulky substituents does not alter crystal structure and close-packed arrangement is observed.

Structural, Mechanistic, and Computational Analysis of the Effects of Anomeric Fluorines on Anomeric Fluoride Departure in 5-Fluoroxylosyl Fluorides

The effects of fluorine substitution at the C-5 center of pyranosyl fluorides on the reactivity at the C-1 anomeric center was probed by studying a series of 5-fluoroxylosyl fluoride derivatives. X-ray structures of their per-O-acetates detailed the effects on the ground-state structures. First-order rate constants for spontaneous hydrolysis, in conjunction with computational studies, revealed that changes in the stereochemistry of the 5-fluorine had minimal effects on the solvolysis rate constants and that the observed rate reductions were broadly similar to those caused by additional fluorine substitution at C-1 but significantly less than those due to substitution at C-2. Differences in the trapping behavior of 5- versus 2-fluoro-substituted glycosyl fluorides with α- and β-glycosidases arise more from differences in steric effects and hydrogen-bonding interactions than from intrinsic reactivity differences.

Deposition of superhydrophobic structures by magnetron discharge

Superhydrophobic surfaces were fabricated with a high water contact angle (CA) of 155° and a low CA hysteresis of 3°. This is achieved by covering the substrate with carbon-based microstructures that take the shape of flowers. These structures, synthesized by pulsed magnetron discharge from acetylene, are confirmed to be fractal by the box-counting determination method. The deposition method is simple, effective, environmentally friendly and applicable to industrial processes involving large flat substrates, like those in the steel and glass coating industries. This work highlights the importance of the surface density of fractal structures for the fabrication of superhydrophobic surfaces. To have a high water CA (>150°), the number of fractal structures per cm2 on a given surface must be as high as possible. If this number decreases, an additional fluorine treatment is necessary to obtain superhydrophobic films.

Synthesis and NMDA receptor affinity of fluorinated dioxadrol analogues

A series of dioxadrol analogues with fluorine substituents in position 4 of the piperidine ring has been synthesized and pharmacologically evaluated. The key step in the synthesis was the fluorination of diastereomeric piperidones 6a and 6c as well as diastereomeric alcohols 9a and 9c with DAST. The reaction of the alcohols 9a and 9c took place with inversion of configuration. After removal of the Cbz-protective group, the NMDA receptor affinities of the resulting secondary amines 8a, 8c, 12b, and 12d were investigated in receptor binding studies. It was shown that the like-configuration of the ring junction was crucial for high NMDA receptor affinity. An axially oriented fluorine atom in position 4 led to 2-(2,2-diphenyl-1,3-dioxolan-4-yl)-4-fluoropiperidine (12d, WMS-2517) with a K(i)-value of 27nM. The NMDA receptor affinity of 8c (WMS-2513) with an additional fluorine atom in equatorial 4-position was slightly reduced (K(i)=81 nM). Both fluorinated dioxadrol derivatives 8c and 12d showed high selectivity against sigma(1) and sigma(2) receptors as well as the polyamine binding site of NR2B receptors.

Synthesis of Polyfluoro Ketones for Selective Inhibition of Human Phospholipase A2 Enzymes

The development of selective inhibitors for individual PLA(2) enzymes is necessary in order to target PLA(2)-specific signaling pathways, but it is challenging due to the observed promiscuity of known PLA(2) inhibitors. In the current work, we present the development and application of a variety of synthetic routes to produce pentafluoro, tetrafluoro, and trifluoro derivatives of activated carbonyl groups in order to screen for selective inhibitors and characterize the chemical properties that can lead to selective inhibition. Our results demonstrate that the pentafluoroethyl ketone functionality favors selective inhibition of the GVIA iPLA(2), a very important enzyme for which specific, potent, reversible inhibitors are needed. We find that 1,1,1,2,2-pentafluoro-7-phenyl-heptan-3-one (FKGK11) is a selective inhibitor of GVIA iPLA(2) (X(I)(50) = 0.0073). Furthermore, we conclude that the introduction of an additional fluorine atom at the alpha' position of a trifluoromethyl ketone constitutes an important strategy for the development of new potent GVIA iPLA(2) inhibitors.

Improved thermal stability of crosslinked PTFE using fluorine gas treatment

Crosslinked PTFE (XF) samples were fluorinated at 293–593 K under 0.7–101 kPa F 2 and for 1 h to 7 days to improve its thermal stability. Because the weight uptake which may be caused by the fluorine addition was detected at room temperature, C C bonds in XF can be fluorinated and the fluorine content was saturated after 72 h. Weights of all samples increased more than that of original XF through additional fluorination of C C bonds, whereas it decreased by the chain-scission to form gaseous fluorocarbons such as CF 4. The intensity ratio in IR spectra of the peaks correspond to the double bond ( CF CF 2) at 1785 cm −1 and the characteristic peaks of PTFE at 1794 cm −1, I PTFE/ I PTFE was smaller for the fluorinated XF rather than that for XF. Average values of heat of crystallization (Δ H c) for all fluorinated XF samples were about 2 J/g higher than that of the original XF. The decomposition temperature calculated from the TG curves increased with increasing reaction temperature and reaction time up to 72 h. Thermal stability of XF was improved through fluorine gas treatment.

Antiproliferative, low-calcemic, fluorinated sulfone analogs of 1α,25-dihydroxyvitamin D 3: Chemical synthesis and biological evaluation

Novel fluorinated sulfone analogs of the hormone 1α,25-dihydroxyvitamin D 3 have been designed and synthesized in order to study the biological effects of fluorine incorporation at the terminus of the C,D-ring side chain. Although biologically active 26,27-hexafluorinated 1α,25-dihydroxyvitamin D 3 analogs have been synthesized previously, this investigation reports the first successful fluorinated series in which trifluoromethyl sulfone analogs present a favorable biological profile. This study shows that two new analogs featuring incorporation of a synthetically simple single trifluoromethyl sulfone group have significantly increased antiproliferative activity while causing desirably low in vivo calciuria relative to that of calcitriol. Incorporation of additional fluorines, as in a perfluorobutyl analog, results in a loss of antiproliferative activity.

Conformational and stereoelectronic investigation in 1,2-difluoropropane: The gauche effect

The effect of attaching an additional fluorine atom at C-2 in 1-fluoropropane (FP), giving 1,2-difluoropropane (DFP), on its conformational equilibrium, is theoretically evaluated. This substitution causes critical implications on the conformer stabilities of DFP (TG, GT and GG conformations) and the steric and electrostatic interactions should favor the conformer with fluorine atoms trans. However, the gauche effect plays a major role in describing the energies balance in DFP, shifting the equilibrium towards the conformation in which the two fluorine atoms are gauche. The origin of this effect is discussed through an NBO analysis, which allows the evaluation of both classical and non-classical (hyperconjugation and bent bonds) interactions as the prevailing factors governing the conformational equilibrium of molecules containing the 1,2-difluoroethane fragment.

Additional fluorine passivation to pyrolytic-N2O passivated ultrathin silicon oxide/Si(100) films

To enhance the reliability of ultrathin silicon oxide/Si(100) films and clarify the effect of fluorine on it, in situ pyrolytic-gas passivation (PGP) using NF3 was simultaneously performed with the previously proposed PGP using N2O. As a result, the following synergistic effects of F and N passivation for the films were confirmed: The electrical characteristics, such as the time-dependent dielectric breakdown lifetime, potential barrier height energy of the oxide, and interface state density, were significantly improved. Quantitative analyses of F and N indicated that this is probably caused by microscopic structural changes in the oxide near the oxide-Si(100) substrate interface. It is, therefore, believed that F passivation effectively contributes to compensate the inconsistent-state bonding sites near the interface that remain with N passivation.

Synergistic Effect of Additional Fluorine on Pyrolytic-N[sub 2]O Passivation for SiO[sub 2]-Si Interfaces

In addition to the previously proposed in situ pyrolytic-gas passivation (PGP) using N 2 O, PGP using NF 3 was simultaneously performed. As a result, a synergistic effect of passivation for ultrathin silicon oxide films was confirmed. That is, the potential barrier height energy of the oxide and the interface state density were significantly improved. This was probably caused by the microscopic structural change in the oxide near the interface due to quantitative analyses of F and N. It is also believed that F passivation effectively contributes to compensate the inconsistent-state bonding sites near the interface that remain with N passivation.

Effects of Fluorine Substitution on the Edge-to-Face Interaction of the Benzene Dimer

To gain some insight into the effects of fluorination on the aromatic-aromatic interactions found in protein-ligand complexes, like those observed in the set of N-(4-sulfamylbenzoyl)benzylamine (SBB) inhibitors bound to Human Carbonic Anhydrase II (HCAII), we have produced potential energy curves for the edge-to-face interactions of a set of fluorinated benzene dimer compounds. All calculations were carried out at the MP2/aug-cc-pVDZ level of theory using the counterpoise method of Boys and Bernardi (Boys, S. F.; Bernardi, F. Mol. Phys. 1970, 19, 553) to account for the basis set superposition error. Fluorine substitutions are made onto the face molecule of the edge-to-face benzene dimer. As one might expect, the substitution of additional fluorines into this system generally resulted in a decrease of the binding energy. It was also found that the positioning of the fluorine substituents on isosubstituted compounds has a large effect on the total binding energy of these types of systems. More specifically, complexes with fluorines that are substituted closer to the hydrogen atoms of the edge benzene will tend to be stabilized by an electrostatic interaction between the partially negative fluorine atoms and the partially positive hydrogen atoms. However, our findings do not explain the recent crystallographic findings for the SBB-HCAII protein-ligand complex, where increased fluorination resulted in closer edge-to-face contacts, which suggests that there are factors, other than edge-to-face aromatic interactions, influencing this system's behavior.

Pharmacodynamics and Pharmacokinetics of Synthetic Mineralocorticoids and Glucocorticoids: Receptor Transactivation and Prereceptor Metabolism by 11β-hydroxysteroid-dehydrogenases

The most important determinants of glucocorticoid (GC) and mineralocorticoid (MC) action in target tissues are the prereceptor metabolism by 11β-hydroxysteroid-dehydrogenases (HSDs) and receptor transactivation. We characterized these parameters for a wide range of steroids often used in clinical practice. The 11-hydroxy-group is essential to GC and MC receptor transactivation. As HSD2 oxidizes 11-hydroxysteroids such as cortisol and prednisolone to inactive 11-ketosteroids such as cortisone and prednisone, GC and MC activity in HSD2-expressing tissues (kidney, colon, placentofetal unit) is strongly regulated by this enzyme. As 6α or 9α fluorination (such as in 9α-fluorcortisol) decreases HSD2 oxidation and increases both GC and MC receptor transactivation, these modifications lead to optimal, but unselective MC and GC receptor occupation. Increased GC and decreased MC receptor transactivation leading to more selective GC activity is reached by the following substituents: 16-methylene (in prednylidene), 16, 17-methyloxazoline (in deflazacort), 16α-methyl (in dexamethasone), 16β-methyl (in betamethasone) and Δ1-dehydroconfiguration (in prednisolone). While modifications at position 16 decrease HSD2 oxidation, the Δ1-dehydroconfiguration increases HSD2 activity leading to an enhanced inactivation of prednisolone compared to all other steroids tested. Our in vitro data allow us to conclude that 9α-fluorcortisol, the most frequently used substance for MC substitution, seems the best choice of available steroids for this approach. Whereas GC selectivity can be improved by hydrophobic substituents at position 16, such as prednylidene and deflazacort, and the Δ1-dehydroconfiguration, maximal GC activity needs additional fluorination at position 6α and/or 9α such as dexamethasone. For GC therapy directed to HSD2-expressing organs, widely used prednisolone does not seem to be the optimal recommendation.

Pharmacodynamics and pharmacokinetics of synthetic mineralocorticoids and glucocorticoids: receptor transactivation and prereceptor metabolism by 11beta-hydroxysteroid-dehydrogenases.

Glucocorticoid (GC) and mineralocorticoid (MC) action in target tissues is determined by prereceptor metabolism by 11beta-hydroxysteroid-dehydrogenases (HSDs) and receptor transactivation. We characterized these parameters for steroids often used in clinical practice. HSD activity was examined in human liver (HSD1) and kidney microsomes (HSD2) and in CHO cells stably transfected with both enzymes. GC and MC transcriptional activity was tested by luciferase assay in CV-1 cells transfected with human GC or MC receptor expression vectors. The 11-hydroxy-group is necessary for GC and MC receptor transactivation. As HSD2 oxidizes 11-hydroxysteroids to inactive 11-dehydrosteroids, GC and MC activity in HSD2-expressing tissues (kidney, colon) is regulated by this enzyme. As 9alpha-fluorination (such as in 9alpha-fluorocortisol) decreases oxidation by HSD2 and increases both GC and MC receptor transactivation, this modification leads to optimal, but non-selective transactivation of both receptors. Increased GC receptor and decreased MC receptor transactivation leading to more selective GC activity is reached using the following substituents: 16beta-methyl (in betamethasone), 16alpha-methyl (in dexamethasone) and triangle up 1-dehydro-configuration (in prednisolone). Whereas the modifications in position 16 decrease oxidation by HSD2, the triangle up 1-dehydro-configuration increases HSD2-activity leading to an enhanced inactivation of prednisolone compared to all other steroids. 9alpha-fluorocortisol, the most frequently used substance for MC-substitution, seems to be the best choice of available steroids for this purpose. Whereas GC selectivity can be improved by hydrophobic substituents in position 16 and the triangle up 1-dehydro-configuration, maximal GC activity needs additional fluorination in position 9alpha (such as in dexamethasone). For GC therapy directed to HSD2-expressing organs, widely used prednisolone does not seem to be the optimal recommendation.

Effect of Fractional Fluorination on the Properties of ATRP Surface-Initiated Poly(hydroxyethyl methacrylate) Films

Acylation of a surface-initiated poly(hydroxyethyl methacrylate) (PHEMA) film with a perfluoroalkyl acid chloride (C7F15COCl) results in a highly blocking film with fluorocarbon side groups that orient at the air−film interface to produce an ultralow-energy surface. The kinetics of the acylation step was monitored with reflectance-absorption infrared spectroscopy to reveal that the rate of fluorination depends on the chain length and solution concentration of the perfluorinated acid chloride as well as the solvent used. By control of the time of exposure to C7F15COCl, films with fractional conversion of the hydroxyl groups to fluorinated esters between 0 and 0.8 were produced. Increasing fractional conversion from 0 to ∼0.2 has a dramatic effect on surface wettability and electrochemical barrier properties as a densely packed, oriented fluorocarbon surface region is formed that greatly reduces water and ion transport. Additional fluorination has no effect on wettability but gradually increases film resistance while lowering film capacitance. These results suggest that structuring of fluorocarbon groups at the outermost surface of the film has a major impact on film properties and establish the minimum content of fluorocarbon groups required to achieve the structured interface via this grafting process.

Structure, Wettability, and Electrochemical Barrier Properties of Self-Assembled Monolayers Prepared from Partially Fluorinated Hexadecanethiols

We report the preparation and characterization of self-assembled monolayers (SAMs) derived from the adsorption of partially fluorinated hexadecanethiols (CF3(CF2)n-1(CH2)mSH; n = 2, 4, 6, and 8; n + m = 16) onto the surface of gold. The quality of the SAMs, as measured by electrochemical impedance spectroscopy, was found to be sensitive to the solvent used as SAMs prepared in dichloromethane exhibited higher resistances and lower capacitances than those prepared in liquid CO2. The extent of fluorination was observed to influence the wettability, structure, and capacitance of the films without significantly affecting their charge-transfer resistance or their stability against exchange by a competing adsorbate. Reflectance-absorption infrared spectra showed that the fluorocarbon chains were oriented more normal to the surface for n = 8 but more parallel to the surface for n = 2. Advancing contact angles of hexadecane increased sharply with fluorination from n = 0 to 4 but slightly with additional fluorination, suggesting that hexadecane is insensitive to CH2 groups that are buried by >4 fluorinated carbon atoms. We also were able to model the dielectric properties of these partially fluorinated SAMs as two capacitors in series: one due to the outer fluorocarbon region and one due to the inner hydrocarbon region. The dielectric constants of the fluorocarbon and hydrocarbon regions of these SAMs were quantified as ∼1.7 and ∼2.3, respectively, and were comparable to the values for the pure polymer counterparts.

Synthesis, Crystal Structure, and Characterization of the First Nb3 Triangular Cluster Compound Bonded to Fluorine Ligands: Association of Nb3IiFi3Fa8La Units and NbIVL6 Octahedra with L = O and F

The synthesis and the crystal structure of the first compound containing Nb(3) triangular clusters bonded to fluorine ligands are presented in this work. The structure of Nb(3)IF(7)L(NbL(2))(0.25) with L = O and F, determined by single-crystal X-ray diffraction, is based on a Nb(3)I(i)F(i)(3)F(a)(8)L(a) unit and a NbL(6) octahedron (tetragonal, space group I4/m, a = 13.8638(3) A, c = 8.9183(2) A, V = 1714.14(7) A(3), Z = 8). Two crystallographic positions (noted L5 and L6) are randomly occupied by fluorine and oxygen with two different F:O occupancies. These L ligands build an octahedral site for a single niobium atom, located between the units. The four L5 ligands of the NbL(6) octahedron are shared with four Nb(3) cluster units, while the two other L6 ligands are terminal. The Nb(3) cluster is face-capped by one iodine and edge-bridged by three fluorine ligands. Two of the three niobium atoms constituting the cluster are bonded to three additional apical fluorine ligands, while the third one is bonded to two fluorines and one L5 ligand. The Nb(3) cluster is linked to six adjacent ones via all the apical fluorine ligands. The developed formula of the unit is therefore Nb(3)I(i)F(i)(3)F(a)(-)(a)(8/2)L(a) according to the Schäfer and Schnering notation. The oxidation state of the single niobium and the random distribution of fluorine and oxygen on the two L sites will be discussed on the basis of structural analysis, the bond valence method, and IR and EPR measurements. The structural results will be compared to those of previously reported niobium compounds containing NbF(6) or Nb(F,O)(6) octahedra.

Influence of fluorooxidizers on scintillation properties of fluorohafnate glass doped with Ce 3+

The influence of fluorination of a batch mixture on the scintillation properties of fluorohafnate glasses in the HfF 4–BaF 2–CeF 3–AlF 3–NaF–InF 3 system was studied. A new technique of batch treatment, comprising additional fluorination by chlorine trifluoride and xenon difluoride in gaseous phase at the elevated temperatures was proposed. Transmission spectra before and after γ-irradiation as well as light yield of the glasses were studied. The radiation hardness of glasses is found to increase as a result of the fluorination treatment. It is suggested that the presence of reduced Hf 3+ ions and oxygen impurities should cause the formation of radiation colouring centres and decrease the radiation hardness of scintillating HfF 4-based glasses, doped with Ce 3+.