Fluoride Substitution Research Articles

Initial Steps of the Sol−Gel Process: Modeling Silicate Condensation in Basic Medium

The initial step of the sol−gel process, that is, the condensation of two molecules of silicic acid has been studied by means of density functional theory. The chosen system represents the reagents under basic reaction conditions. Calculations were performed in the gas phase as well as by employing a solvent model for aqueous solution. For both systems, a reaction intermediate with one pentacoordinated silicon center was found as the most stable structure. The influence of intramolecular hydrogen bonds on the stability of the intermediate structure is discussed, and different pathways for the subsequent condensation step are investigated. Furthermore, the effect of fluoride substitution on the reaction path is investigated.

Role of chemical pressure in enhancing the transition temperature (Tc) and upper critical field (Hc2) in the Y-doped Ce-oxyfluoride superconductor

Structural and superconducting properties of yttrium substituted Ce1-xYx(O/F)FeAs superconductors have been investigated for the first time. All the compounds crystallize in the tetragonal ZrCuSiAs structure type. There is a decrease in both the a and c lattice parameters on increasing yttrium substitution (with fixed F content) along with a substantial enhancement of the superconducting transition temperature (Tc) and upper critical field (Hc2) indicating the influence of chemical pressure. Interestingly the maximum Tc (~48 K) was observed for an intermediate composition (Ce0.5Y0.5O0.9F0.1FeAs) which is higher than either of the parent Y or Ce-compounds, (YO0.9F0.1FeAs (~10 K) and Ce(O/F)FeAs (~42 K)). The transition temperature was also found to be nearly independent of the electron -doping introduced by fluoride substitution (0.1 to 0.2 moles per formula unit) indicating the significance of the charge reservoir layer (Ce-O). The yttrium substituted (fluoride free) compositions of the type, Ce1-xYxOFeAs were found to be semimetallic like the parent compound CeOFeAs with the shift in the anomaly temperature towards low temperature on substitution of yttrium ions. Hall coefficient and thermopower measurements show an increase in charge carriers (electrons) through Y-doping in fluorine doped CeOFeAs.

Multipole Model for the Electron Group Functions Method

Electron groups provide a natural way to introduce local concepts into quantum chemistry, and the wave functions based on the group products can be considered as a framework for constructing efficient computational methods in terms of "observable" parts of molecular systems. The elements of the group wave functions (electronic structure variables) can be optimized by requiring the number of operations proportional to the size of the molecule. This directly leads to computational methods linearly scaling for large molecular systems. In the present work we consider a particular case of such a wave function implemented for the semiempirical NDDO Hamiltonian. The electron groups are expressed in terms of optimized atomic (hybrid) orbitals with chemical bonds described by geminals and the delocalized groups described by Slater determinants (with or without spin restriction). This scheme is very fast by itself but its speed is considerably limited by the computations of the interatomic Coulomb interactions. Here we develop a consistent method based on group functions which uses the multipole scheme for interatomic interactions. The explicit usage of the atomic multipoles makes the method extremely fast, although the numerical efficiency is largely achieved due to the local character of the electron groups involved. We discuss numerical characteristics of the new method as well as its possible parametrization. We apply this method to study dodecahedral water clusters with hydrogen fluoride substitution and base the analysis on the exhaustive calculation of all symmetry-independent hydrogen-bond networks.

Aromatic C–F activation by complexes containing the {Pt2S2} core via nucleophilic substitution: a combined experimental and theoretical study

The C-F bond activation of perfluorobenzene and perfluoropyridine have been achieved by means of the complex [Pt(2)(mu-S)(2)(dppp)(2)], where dppp denotes 1,3-bis(diphenylphosphino)propane. The reaction with the first substrate requires a long time (five days) and high temperature (reflux in toluene) to yield [Pt(o-S(2)C(6)F(4))(dppp)] and [Pt(3)(mu(3)-S)(2)(dppp)(3)]F(2), and involves replacement of two fluorides in the ortho position. In contrast, the reaction with perfluoropyridine is much faster (15 min at 0 degrees C) yielding [Pt(2)(mu-S){mu-(p-SC(5)F(4)N)}(dppp)(2)]F, which implies the C-F activation in the para position with respect the pyridine nitrogen. The mechanism of both reactions has been studied computationally and the geometries of the transition states are consistent with an S(N)Ar mechanism where a sulfido bridging ligand replaces the fluoride anion. The energy barriers corresponding to the first and the second fluoride substitution are 131.7 and 137.1 kJ mol(-1) for perfluorobenzene and 85.9 and 142.7 kJ mol(-1) for perfluoropyridine, respectively. The different energy barrier of the first substitution explains the different experimental conditions required and the various products obtained for these reactions.

Radiosynthesis of 8-Fluoro-3-(4-[18F]Fluorophenyl)-3,4-Dihydro-1-Isoquinolinamine ([18F]FFDI), a Potential PET Radiotracer for the Inducible Nitric Oxide Synthase

A selective and potent iNOS inhibitor, 8-fluoro-3-(4-fluorophenyl)-3,4-dihydro-1-isoquinolinamine (IC50 =0.16 μM) has been developed recently [8]. Based on that inhibitor, a novel PET imaging tracer intended for in vivo assessment of the iNOS, the F-18 labeled 8-fluoro-3-(4-[18F]fluorophenyl)-3,4-dihydro-1-isoquinolinamine ([18F]FFDI) was synthesized. [18F]FFDI was first prepared with radiochemical yield of 12-28% (with decay correction to EOS), low specific radioactivity, and low chemical purity by the direct aromatic nucleophilic substitution of 8-fluoro-3-(4-nitrophenyl)-3,4-dihydro-1-isoquinolinamine. Here an alternate two step synthesis is reported, in which nucleophilic [18F]fluoride substitution of 4-nitro-benzaldehyde and 4-N,N,N-trimethylammoniumbenzaldehyde triflate yielded 4-[18F]fluorobenzaldehyde, which was then converted to N-Trimethylsilyl-4-[18F]fluorobenzaldimine. N-Trimethylsilyl-4-[18F]fluorobenzaldimine reacted with the 2-fluoro-6-methyl-benzonitrile to form [18F]FFDI. The total synthesis took 115-128 min and the isolated yield was in the range of 15-26% (with decay correction to EOS), the radiochemical purity of the final product was higher than 99% and the specific radioactivity at the end of synthesis was typically 1212 ± 870 Ci/mmol (n=3). The final product was prepared as a sterile saline solution suitable for in vivo use on animals.

Microwave-induced nucleophilic [ 18F]fluorination on aromatic rings: Synthesis and effect of halogen on [ 18F]fluoride substitution of meta-halo (F, Cl, Br, I)-benzonitrile derivatives

The meta-halo-3-methylbenzonitrile derivatives (-F, -Cl, -Br, -I) were synthesized as model compounds to study reactivity towards aromatic nucleophilic substitution. A single-mode microwave system was incorporated into a commercial radiochemical synthetic module for 18F labeling. Labeling yields of 64% for fluoro-, 13% for bromo- and 9% for chloro-precursors were achieved in DMSO in <3 min. The observed order of reactivity of the leaving groups toward aromatic nucleophilic substitution was F⪢Br>Cl⋙I.

Consequences of Fluoride Incorporation on Properties of Apatites

Fluoride, when incorporated in the apatite, stabilizes the structure. The purpose of this study was to determine the consequences of fluoride (F) substitution on the physico-chemical properties of apatites. F-containing apatites were prepared by precipitation or by hydrolysis of CaHPO4 in solutions containing different F concentrations and characterized using x-ray diffraction, FT-IR spectroscopy, scanning electron microscopy, thermogravimetry and chemical analyses. Results showed that F incorporation have the following effects: (a) decrease in a-axis dimension, (b) increase in crystal size and thickness, (c) decrease in calcium deficiency, and (d) lower solubility.

1-[18F]Fluoroethyleneglycol-2-nitroimidazoles, a new class of potential hypoxia PET markers

1-[2-(2-Fluoroethoxy)ethyl]-2-1H-nitroimidazole (3a), 1-{2-[2-(2-fluoroethoxy)ethoxy]ethyl}-2-1H-nitroimidazole (3b) and 1-(2-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}ethyl)-2-1H-nitroimidazole (3c) were synthesized in a two step sequence.Coupling the ditosylate of di-, tri- or tetraethylene glycol with 2-nitroimidazole followed by fluoride substitution afforded the reference compounds in high yield and18F labeling gave the corresponding markers in 70-82% radiochemical yield.

Sol–Gel Preparation and Properties of Fluoride‐Substituted Hydroxyapatite Powders

Hydroxyapatite (HA) and fluor‐hydroxyapatite (FHA) powders were synthesized by a sol–gel method for usage as bone filler and drug carrier. Calcium nitrate and triethyl phosphite were used as precursors under an ethanol–water‐based solution. Different amounts of ammonium fluoride (NH4F) were incorporated for the preparation of FHA powders. With heat treatment above 400°C, a characteristic apatite phase was observed for all the sol–gel powders. However, the crystallization temperature decreased with increasing fluoride addition. The tricalcium phosphate (TCP) phase formed in the pure HA powder above 800°C was attenuated in the FHA powders, confirming an enhanced phase stability of the FHA powders. Increasing the F− addition improved crystallinity and increased the crystallite size, as was determined from X‐ray diffraction (XRD) analyses. The lattice parameters of the heat‐treated powders varied corresponding to the fluoride addition, i.e., a gradual decrease in the a‐axis, while little change in the c‐axis was observed with increasing fluoride addition, indicating a nearly complete substitution of fluoride within the apatite lattice. However, little difference was observed with heat‐treatment temperatures (400°–1000°C). The powders substituted with fluoride exhibited reduced dissolution rates in an in vitro solution as compared with the pure HA powder, suggesting the possibility of tailoring bioactivity with fluoride substitution.

Sintered hydroxyfluorapatites. Part II: Mechanical properties of solid solutions determined by microindentation

Fluoride substitution within hydroxyapatite is an important occurrence for biological apatites and is a promising approach for the chemical modification of synthetic hydroxyapatite. Limited information on the influence of fluoride substitution for hydroxyl groups on the mechanical properties has provided the rationale for this study. Hydroxyfluorapatites with 0%, 20%, 40%, 60%, 80% and 100% replacement of hydroxyl groups with fluoride ions were assessed for hardness, elastic modulus, fracture toughness and brittleness using microindentation of sintered pellets. The production of samples with a similar grain size and density allowed the influence of fluoride on mechanical properties to be determined. It was found that the hardness remains unaffected until 80% replacement of hydroxyl groups with fluoride, after which the hardness rapidly increases. The elastic modulus increases linearly with fluoride content. Fracture toughness is improved with fluoride incorporation into the lattice and reaches a peak of 1.8 for a 95% dense sintered pellet with a 60% fluoride replacement, followed by a rapid decrease at higher fluoride concentrations. The brittleness index is lowered to a minimum at 60%, after which a rapid increase occurs. High fluoride levels are unfavourable from a mechanical perspective, are not recommended for biomaterials, and can lead to a higher incidence of fracture where sodium fluoride, for treatment of osteoporosis, may produce a highly fluoridated hydroxyapatite.

A subset of highly effective propafenone-type multidrug resistance modulators lacks effects on cardiac action potential and mechanical twitch parameters of rat papillary muscles.

In this study, we tested a series of 12 previously identified, highly effective propafenone-type multidrug resistance (MDR) modulators for their possible undesirable effects on cardiac tissue. We used rat papillary muscle preparations and quantitatively determined the potency of these substances to block action potential (AP) upstroke velocity (Vmax) and to prolong APD50. Simultaneously, the effects on isometric twitch parameters were evaluated. Concentration-response curves were obtained for all parameters. Within a subset of the compounds, we found a significant rank correlation (r' = 0.87; p < 0.05) between potencies to block Vmax (kiVmax) and to inhibit daunomycin efflux in MDR cells (IC50). Surprisingly, the most lipophilic compounds with additional aromatic side chains completely lacked effects on AP and mechanical twitch parameters, although they are the most effective MDR modulators. Additional structural modifications such as fluoride substitution of the aromatic ring, introduction of arylpiperazine or piperidine side chains, as well as modifying the hydrogen bond acceptor strength of the carbonyl group did not reestablish cardiac side effects. In contrast, when these substances were truncated at the phenylpropiophenone moiety of the propafenone core structure, cardiac effects reoccurred. We conclude that aromatic substituents in the vicinity of the nitrogen atom prevent interaction with ion channels, likely due to steric hindrance, and are thus a prerequisite for eliminating unwanted cardiac effects.

Potentiometric and 19F nuclear magnetic resonance spectroscopic study of fluoride substitution in the GaAl 12 polyoxocation: implications for aluminum (hydr)oxide mineral surfaces

Fluoride replacement of oxygens in the GaO 4Al 12(OH) 24(H 2O)127+(aq) molecule [GaAl 12] was studied via 19F nuclear magnetic resonance (NMR) at 4 < pH < 5 and 278 K in order to elucidate similar reactions at the surfaces of clays. Peaks are identified in the 19F-NMR spectra that correspond to both terminal and bridging fluorides on the GaAl 12 molecule, with relative peak positions similar to those previously identified in fluoridated aluminum (hydr)oxide mineral surfaces (Nordin, J. P., Sullivan, D. J., Phillips, B. L., and Casey, W. H. [1999], “Mechanisms for fluoride-promoted dissolution of bayerite [β-Al(OH) 3(s)] and boehmite [γ-AlOOH(s)]- 19F-NMR spectroscopy and aqueous surface chemistry,” Geochim. Cosmochim. Acta 63, 3513–3524). Fluoride substitutes for oxygen at three different sites in the GaAl 12 molecule, but at dramatically different rates. The kinetics of fluoride substitution follow a rate law that includes parallel and reversible transfer of fluoride from nonbridging sites to the two bridging sites. The essential features of the rate law are as follows: (1) fluoride replaces bound water molecules (η-OH 2) within minutes at 278 K at rates that are quantitatively similar to fluoride uptake by Al(H 2O)63+(aq) to form AlF 2+(aq) at similar conditions; (2) fluoride substitutes onto the two topologically distinct μ 2-OH sites at different rates, as was previously observed for oxygen exchange, but here, the reaction is complete in hours to days at 278 K. Most importantly, rates of fluoride substitution onto μ 2-OH sites are 10 2 times more rapid than the corresponding rates of oxygen exchange with bulk waters, indicating that fluoride considerably labilizes the molecule, as is also observed at the surfaces of minerals. The largest cause of this labilization is the reduced molecular charge on the GaAl 12 upon replacement of bound waters by fluoride, which for mineral surfaces corresponds to a reduction in surface charge density.

Fluoride Substitution on Polypyrrole during Electrochemical Synthesis in the Presence of N(Bu)4BF4

Strong evidence of fluoride substitution on the pyrrole ring during electrolysis has been observed in a systematic structural and thermal analyses of polypyrrole doped with BF 4 - by durect insertion probe-mass spectrometry. To get a better understanding, not only plypyrrole samples doped with different dopant levels but also dedoped polypyrrole samples, mechanical mixtures of undopped polypyrrole and N(Bu) 4 BF 4 were analyzed using pyrolysis mass and FTIR spectroscopy techniques.

Energy transfer from Tm 3+: [formula omitted] to Dy 3+: [formula omitted] in oxyfluoride tellurite glasses

Thermal analysis and optical properties indicate that Tm 3+ and Dy 3+ co-doped oxyfluoride tellurite glasses can be excellent candidates for fiber amplifiers at 1.47 μm region. Substitution of GeO 2 and In 2O 3 in tellurite glasses increased the glass stability without decreasing the lifetime of the upper Tm 3+: 3 H 4 level, and the fluoride substitution increased lifetime of excited energy levels of Tm 3+ ion. Dy 3+ co-doping in the Tm 3+-doped oxyfluo⋮appride tellurite glasses enhanced the depopulation of the Tm 3+: 3 F 4 level through an energy transfer Tm 3+: 3 F 4 →Dy 3+: 6 H 11/2 . We report the measurements of crystallization, glass transition temperatures, and optical properties of Tm 3+, Dy 3+ co-doped oxyfluoride tellurite glasses.

Characterization of the calcium biomineral in the radular teeth of Chiton pelliserpentis.

The radula in a group of molluscan invertebrates, the chitons (Polyplacophora), is a ribbon-like apparatus used for feeding and which bears a series of distinctive mineralized teeth called the major lateral teeth. While some chiton species deposit only iron biominerals in these teeth, many others deposit both iron and calcium. In this study, the calcium biomineral in the teeth of one of the latter types of species, the Australian east-coast chiton, Chiton pelliserpentis, has been isolated and examined for the first time. Spectroscopic and crystallographic techniques have identified the biomineral as a carbonate-substituted apatite with significant fluoride substitution also likely. Fourier-transform infrared and laser Raman spectroscopy indicated that the carbonate content was less than that of either bovine tibia cortical bone or human tooth enamel. X-ray diffraction analysis showed the biomineral to be poorly crystalline due to small crystal size and appreciable anionic substitution. The lattice parameters were calculated to be a = 9.382 A and c = 6.883 A, which are suggestive of a fluorapatite material. It is postulated that structural and biochemical differences in the tooth organic matrix of different chiton species will ultimately determine if the teeth become partly calcified or iron mineralized only.

Nanocrystals of magnesium and fluoride substituted hydroxyapatite

Hydroxyapatite nanocrystals synthetized in the presence of different concentrations of magnesium and fluoride ions in solutions – 1, 5 and 10 at.% have been submitted to a structural and chemical characterization. The syntheses were carried out in the presence of low molecular weight polyacrilic acid, which has been verified to inhibit hydroxyapatite crystallization. The polyelectrolyte is adsorbed into the crystals during the synthesis and provokes a reduction of the mean crystal sizes. The reduction is greater along the direction orthogonal to the c-axis, suggesting a preferential adsorption of the polyelectrolyte on the crystalline faces parallel to the c-axis. Both magnesium and fluoride can be incorporated into the hydroxyapatite structure. On the basis of the values of the lattice constants and of the magnesium relative content of the solid phase, it can be suggested that probably just a part of magnesium is substituted for calcium, the remainder being adsorbed on the crystal surface. However, magnesium destabilizes the apatitic structure favouring its thermal conversion into β-tricalcium phosphate, and displays an inhibiting effect on the crystallization of hydroxyapatite. This last effect is enhanced by the simultaneous presence of polyacrylic acid. Fluoride substitution for hydroxyl ions into hydroxyapatite structure induces a slight increase of the crystal sizes along the c-axis direction. The data indicate that the experimental approach can be successfully used to prepare nanoapatite with crystallinity, crystal dimensions, composition, structure and stability very close to those characteristic of biological apatites.

Conversion of trypsin into a selenium- containing enzyme by using chemical mutation

A chemical derivative of trypsin, selenotrypsin, was prepared to imitate glutathione peroxidase (GPX) by converting active serine residues in the active site of trypsin into selenocysteines. The strategy for preparation of selenotrypsin contained selective sulfonation by phenylmethanesulfonyl fluoride and nucleophilic substitution by NaHSe. Seleno-trypsin displayed enzyme activity of GPX, which is 150U/(mol. The kinetic properties of selenotrypsin was demonstrated to be similar to that of native GPX. © Rapid Science Ltd. 1998

Solvent exchange in AlF x (H 2O 6− x3− x (aq) complexes: Ligand-directed labilization of water as an analogue for ligand-induced dissolution of oxide minerals

We demonstrate, using dynamic 17O-NMR spectroscopy, that fluoride ions in the inner-coordination sphere of AlF x (H 2O) 6−x 3−x(aq) complexes (0 ≤ x ≤ 2) progressively enhance, by orders of magnitude, the rate of exchange of waters from the innersphere to the bulk solvent. At 298K, the rate of the elementary ligand-exchange reaction increased approximately linearly with each fluoride substitution from about 2 s −1 for the fully hydrated [Al(H 2O) 6 3+(aq)] complex to about 2 × 10 4 s −1 for the difluoro [AlF 2(H 2O) 4 +(aq)] complex. A similar effect can be expected for isoelectronic complexes, such as the hydrolysis product: AlOH(H 2O) 5 2+(aq). By hypothesis, a similar phenomenon accounts for fluoride-enhanced release of metals from a dissolving mineral surface. If so, it should be possible to predict the effectiveness of different adsorbed ligands to enhance dissolution of minerals from spectroscopic rate measurements on dissolved complexes, as was recently shown for aminocarboxylate ligands and NiO(s) (Ludwig et al., 1995, 1996).

Theoretical studies on nucleophilic vinylic fluoride substitution

Theoretical studies on nucleophilic vinylic fluoride substitution

Theoretical studies on nucleophilic vinylic fluoride substitution

The reaction of vinyl fluoride with CN − has been studied by using the DFTB3YLP/6-31 + G(d) method. Topological features of the electron density distribution ϱ( r) and the analysis of the Laplacian concentration − ▽ 2 ϱ( r) have also been utilized for describing this reaction. The results show that this nucleophilic substitution is mainly of π attack with a barrier height of 14.8 kcal mol −1 which is 17.91 kcal mol −1 more favourable than the σ attack.