Optimization of Automated Synthesis of 2-[18F]Fluoro-2-deoxy-D-glucose Involving Base Hydrolysis

Synthesis of 2-[¹⁸F]fluoro-2-deoxy-D-glucose ([¹⁸F]FDG) involving base hydrolysis was optimized. Fluorine-18 was isolated from irradiated water to more than 90% by sorption of [^{1 8}F]fluoride on QMA anion-exchange resin, which was followed by elution with a 96 : 4 (by volume) acetonitrile-water mixture containing Kryptofix 2.2.2 and potassium carbonate (molar ratio 2 : 1). This composition is the best for preparing the complex [K/K2.2.2]^{+ 18}F^- used in nucleophilic fluorinations. No additional azeotropic drying is required. Base hydrolysis under optimized conditions (40-45°C), followed by neutralization with HCl, removal of traces of the solvent, and purification of the final product on a combined SCX/Alumina N column, yielded [^{1 8}F]FDG of high radiochemical (>99%) and chemical purity with minimal product loss. With an RB-86 robotic system (Anatech, Sweden), the synthesis time was 38 min. The procedure is used in the Institute of Human Brain, Russian Academy of Sciences for routine synthesis of FDG; the radiochemical yield of the product by the end of synthesis (EOS) is reproducibly high: 63±3% (n = 40).     

Preparation of [1 8F]Flumazenil, a Potential Radioligand for PET Imaging of Central Benzodiazepine Receptors, by Isotope Exchange

[^{1 8}F]Flumazenil was prepared by a new route: isotope exchange of ¹⁹F for ¹⁸F under standard conditions of nucleophilic fluorination using the complex [K/K2.2.2]^{+ 18}F^-. The radiofluorination efficiency was 62±8% (n = 8) under the following conditions: solvent dimethyl sulfoxide, 5 min, 130°C, flumazenil sample weight 2 mg, and equimolar ratio of potassium cryptate ([K₂CO₃/K2.2.2]) to flumazenil. Yield of the product after purification by solid-phase exraction on a tC18 column, corrected for ¹⁸F decay, 47±3% (n = 5). The identity of [^{1 8}F]flumazenil was confirmed by radio-HPLC using three different chromatographic systems.     

Crystal Structure of Rb[UO2(SO4)F]

Single crystal of Rb[UO₂(SO₄)F] (I) was studied by X-ray diffraction [rhombic system, space group Pca2 ₁, Z = 12, unit cell parameters: a = 25.393(3), b = 6.735(1), c = 11.496(3) Å]. The main structural units of crystals of I are [UO₂(SO₄)F]^- layers belonging to the crystallochemical group AT³M² (A = UO₂ ^{2 +}) of uranyl complexes and combined into three-dimensional framework by electrostatic interactions involving interlayer rubidium ions.     

Modification of Automatic Synthesis of [<Superscript>18</Superscript>F]Fluoromisonidazole on a GE TracerLAB Fx F-N Synthesis Module

A procedure for preparing 1-(2-hydroxy-3-[¹⁸F]fluoropropyl)-2-nitroimidazole ([¹⁸F]fluoromisonidazole, [¹⁸F]FMISO) on a commercially available GE TracerLAB Fx F-N synthesis module was developed. The product obtained meets all the requirements of the European Pharmacopoeia (8th ed.) for clinical use. Its decay-corrected radiochemical yield is 59 ± 4% (n = 5).     

Synthesis of 2-[18F]Fluoro-L-tyrosine and comparative study of its uptake by rat glioma 35 tumor and by induced inflammation focus in experimental animals

2-[¹⁸F]Fluoro-L-tyrosine (2-[¹⁸F]FTYR), a labeled fluorinated analog of tyrosine, was prepared using chiral phase-transfer catalysis. The radiochemical yield of 2-[¹⁸F]FTYR corrected for radioactive decay was 25±6% (n = 15) at a synthesis time of 110–120 min, including semipreparative HPLC purification. The radiochemical and chemical purity of the product exceeded 99%, and the enantiomeric purity was 98.2±0.7% (n = 15). The uptake of 2-[¹⁸F]FTYR by tumors and abscesses in laboratory animals was studied. The ratios of radioactivity uptake by tumor or imflamed tissue to that of an intact muscle tissue were calculated. Within the time of experiment, the tumor/muscle ratio exceeds the abscess/muscle ratio. The results obtained allow 2-[¹⁸F]FTYR to be considered as potentially useful radiotracer for differential diagnostics of tumors and inflammations by PET.     

A Robust Molecular Porous Material for C2H2/CO2 Separation

A molecular porous material, MPM-2, comprised of cationic [Ni₂(AlF₆)(pzH)₈(H₂O)₂] and anionic [Ni₂Al₂F₁₁(pzH)₈(H₂O)₂] complexes that generate a charge-assisted hydrogen-bonded network with pcu topology is reported. The packing in MPM-2 is sustained by multiple interionic hydrogen bonding interactions that afford ultramicroporous channels between dense layers of anionic units. MPM-2 is found to exhibit excellent stability in water (>1 year). Unlike most hydrogen-bonded organic frameworks which typically show poor stability in organic solvents, MPM-2 exhibited excellent stability with respect to various organic solvents for at least two days. MPM-2 is found to be permanently porous with gas sorption isotherms at 298 K revealing a strong affinity for C₂H₂ over CO₂ thanks to a high (ΔQ_st)_AC [Q_st (C₂H₂) − Q_st (CO₂)] of 13.7 kJ mol⁻¹ at low coverage. Dynamic column breakthrough experiments on MPM-2 demonstrated the separation of C₂H₂ from a 1:1 C₂H₂/CO₂ mixture at 298 K with effluent CO₂ purity of 99.995% and C₂H₂ purity of >95% after temperature-programmed desorption. C-H···F interactions between C₂H₂ molecules and F atoms of AlF₆³⁻ are found to enable high selectivity toward C₂H₂, as determined by density functional theory simulations.     

Photoluminescence and electrochemistry behavior of well-dispersible poly-N-[5-(8-quinolinol)ylmethyl]aniline/nano-TiO2 composite

Well-dispersible poly-N-[5-(8-quinolinol)ylmethyl]aniline/nano-TiO₂ composite was synthesized by the surface modification of nano-TiO₂ particles using poly-N-[5-(8-quinolinol)ylmethyl] (PANQ), and it was characterized by Fourier-transform infrared spectroscopy, photoluminescence spectroscopy, thermogravimetric analysis and scanning electron microscope, as well as conductivity and cyclic voltammogram were given. The conductivity of this composite was 2.1 × 10⁻² S cm⁻¹ at 25 °C, and showed good redox reversibility. It was easy to cast a transparent conducting film with photoluminescent property.     

Synthesis of [<Superscript>18</Superscript>F]-<Emphasis Type="Italic">L</Emphasis>-DOPA radiopharmaceutical on a modified GE TracerLAB Fx F-E platform

A procedure was developed for preparing [¹⁸F]-5-hydroxy-2-fluoro-L-thyrosine ([¹⁸F]-fluoro-L-dihydroxyphenylalanine, [¹⁸F]-L-DOPA) radiopharmaceutical on modified commercially available GE Tracer-LAB Fx F-E platform. This modification can be used for preparing both [¹⁸F]-L-DOPA and any other radiopharmaceuticals by electrophilic radiofluorination. The procedure allows preparation of the product meeting all the requirements of European Pharmacopoeia (8th ed.) for clinical use with the decay-corrected radiochemical yield of 20 ± 3% (n = 3).     

Use of 2-[<Superscript>18</Superscript>F]fluoroethyl bromide in synthesis of <Emphasis Type="Italic">O</Emphasis>-(2′-[<Superscript>18</Superscript>F]fluoroethyl)-<Emphasis Type="Italic">L</Emphasis>-tyrosine,a radiotracer for PET diagnostics of brain tumors

The possibility of using 2-[¹⁸F]fluoroethyl bromide ([¹⁸F]FEB) as labeled reagent for selective O-[¹⁸F]fluoroethylation of phenolic group in the presence of an unprotected amino group in an amino acid molecule was demonstrated by the example of the synthesis of O-(2′-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET), one of the most promising PET radiotracers for evaluating the rate of transport of amino acids into a tumor tissue. The labeled reagent was prepared by [¹⁸F]fluorination of 2-bromoethyl tosylate with the complex [K/K2.2.2]/[¹⁸F] in o-dichlorobenzene (110°C, 10 min) and was transferred with a nitrogen flow into a solution of the substrate (L-tyrosine, NaOH, dimethyl sulfoxide or dimethyl sulfoxide/o-dichlorobenzene). The reaction with the substrate was performed for 20 min at 100°C; the degree of O-[¹⁸F]fluoroethylation was 75%. [¹⁸F]FET was prepared with a high radiochemical purity (>95%); the total synthesis time, including HPLC purification, was 60 min, and the unoptimized radiochemical yield (corrected for the radioactive decay) was about 20%. The synthesis was performed with an Anatech RB-86 laboratory robot.     

Prepatation of [18F]Fluorobenzyl Bromides for Their Use in Asymmetric Synthesis of Fluorinated α-Amino Acids,Radiotracers for Positron Emission Tomography

Procedures were developed for synthesis of 3,4-methylenedioxy-6-[^{1 8}F]fluorobenzyl bromide I and 2-[^{1 8}F]fluoro-4-methoxybenzyl bromide Ia, which are intermediates in asymmetric synthesis of fluorinated -amino acids used in positron emission tomography (PET). The bromination procedures involving two brominating agents, an ethereal solution of HBr or triphenyldibromophosphorane in various solvents, as well as purification procedures, were compared. An optimized procedure was suggested for synthesis of I and Ia using an Anatech robotic system; the total synthesis time is 45-48 min. The radiochemical yield of I and Ia, corrected for the ^{1 8}F decay, was 35-40 and 60-65%, respectively. The suggested scheme can be adapted to modern automated modules for production of radiopharmaceuticals.     

The structure of the unidirectionally solidified Al-Al2Au eutectic

The structure of a number of unidirectionally solidified Al-Al₂Au alloys of eutectic and off-eutectic compositions has been investigated over a wide range of growth rates (1.6×10^–4 to 1.66×10^–2cm sec^–1) using a thermal gradient of approximately 80 to 100 lamellar interface || (001)_{Al 2 Au} || (01 1) _Al [ 1 1 0 ]_{Al 2 Au} || [ 1 0 0 ] _Al growth direction of lamellae and rods || [ 1 1 0 ]_{Al2 Au} || [ 1 0 0 ]_Al \begin{gathered} lamellar interface \left\| {(001)_{Al_{ 2} Au} } \right.\left\| {(01 1)} \right._{Al} \hfill \\ \left[ {1 1 0} \right]_{Al_{ 2} Au} \left\| {\left[ {1 0 0} \right]} \right._{Al} \hfill \\ growth direction of \hfill \\ lamellae and rods \left\| {\left[ {1 1 0} \right]_{Al_2 Au} \left\| {\left[ {1 0 0} \right]_{Al} } \right.} \right. \hfill \\ \end{gathered}     

Superconducting Cuprates with Charge Reservoir Consisting of either Peroxide-type Oxygen or H2O

Two novel homologous series of superconductive M-m2(n-1)n copper oxides with the charge-reservoir block consisting of either peroxide-type oxygen [0 ^(Ba) 2(n-1)n phases] or water [H-m2(n-1)n phases] are reported. The former phases with T _c 's higher than 100 K are obtained in the Ba-Ca-Cu-O system from high-pressure synthesis under oxidizing conditions. When exposed to open air, the latter phases spontaneously form from the highly unstable 0 ^(Ba) 2(n-1)n phases due to incorporation of H ₂ O molecules into the structure when exposed to open air. Besides water, the phase change is believed to involve additional protons from a redox reaction between water and the highly oxidized copper/peroxide-type oxygen of the 0 ^(Ba) 2(n-1)n phases. Upon the phase change the 0 ^(Ba) 2(n-1)n phases are reduced considerably, as was also confirmed by wet-chemical redox analysis.     

Microemulsion loaded hydrogel as a promising vehicle for dermal delivery of the antifungal sertaconazole: design,optimization and ex vivo evaluation

The purpose of the present study was to develop and optimize sertaconazole microemulsion-loaded hydrogel (STZ ME G) to enhance the dermal delivery and skin retention of the drug. Following screening of various oils for maximum drug solubility, 12 pseudoternary phase diagrams were constructed using oils (Peceol^®, Capryol^® 90), surfactants (Tween^® 80, Cremophor^® EL), a cosurfactant (Transcutol^® P) and water. A 2¹ × 3¹ × 2¹ × 3¹ full factorial design was employed to optimize a ME of desirable characteristics. The MEs were formulated by varying the oil type, oil concentration, surfactant type and surfactant: cosurfactant ratio. Optimized ME formulae F22 [5% Peceol^®, 55% Tween^® 80: Transcutol^® (1:2), 40% water] and F31 [5% Peceol^®, 55% Cremophor^® EL: Transcutol^® (1:2), 40% water] acquired mean droplet size of 75.21 and 8.68?nm, and zeta potential of 34.65 and 24.05?mV, respectively. Since F22 showed higher STZ skin retention during ex vivo studies (686.47?μg/cm²) than F31 (338.11?μg/cm²); hence it was incorporated in 0.5% Carbopol 934 gel to augment STZ skin retention capability. STZ ME G exhibited higher STZ skin retention (1086.1?μg/cm²) than the marketed product “Dermofix^® cream” (270.3?μg/cm²). The antimycotic activity against C.albicans revealed increased zones of inhibition for F22 and STZ ME G (35.75 and 30.5?mm, respectively) compared to Dermofix^® cream (26?mm). No histopathological changes were observed following topical application of STZ ME G on rats’ skin (n?=?9). Overall, the obtained results confirmed that the fabricated formulation could be a promising vehicle for the dermal delivery of STZ.     

Fabrication and characteristics of polyfluorene based organic photodetectors using fullerene derivatives

The characteristics of organic photodetectors (OPDs) by solution process using one of the polyfluorene derivatives poly(9,9-dioctylfluorene-co-bithiophene) (F8T2) and two fullerene derivatives [6-6]phenyl-C61-butyric acid methyl ester (PCBM) or N-Ts aziridinofullerene (TsAF) are investigated. F8T2:PCBM devices showed good rectifying characteristics in a dark state and photosensitive characteristics, and fast frequency responses. Weight ratio of 1:1 device showed larger photocurrent than 1:4 device and obtained over 50 MHz of cutoff frequency under reverse bias voltage of 10 V. This result suggests that F8T2:PCBM device can be applied to a photodetector for detecting several tens of megahertz optical signals under blue light irradiation. The polarity of J–V characteristics of F8T2:fullerene derivative device is strongly affected by charge injection and extraction between fullerene derivative and electrodes.     

Studies on ionic transport properties of a new Ag+ ion conducting composite electrolyte system (1−x)[0·75 AgI: 0·25 AgCl]:xSnO2

A new Ag⁺ ion conducting composite electrolyte system (1−x)[0·75 AgI: 0·25 AgCl]:xSnO₂ using a quenched/annealed [0·75 AgI: 0·25 AgCl] as host compound in place of conventional host AgI, has been investigated. The effects of various preparation methods and soaking time are reported. The composition 0·8[0·75 Agl: 0·25 AgCl]:0·2SnO₂ exhibited optimum conductivity (σ = 8·4 × 10⁻⁴S/cm) with conductivity enhancement of ∼ 10¹ from the annealed host at room temperature. Transport property studies such as electrical conductivity (σ) as a function of temperature using impedance spectroscopy technique, ionic transference number (t _ion) using Wagner’s d.c. polarization method and ionic mobility (μ) by transient ionic current technique were carried out on the optimum conducting composition. The mobile ion concentration (n) was calculated from ‘σ’ and ‘μ’ data.     

Mass Spectrometry Study of C60 and C60-NiF2 Fluorination with Molecular Fluorine

Abstract

Fluorination of [60]fullerene and [60]fullerene-NiF₂(s) has been studied in situ by Knudsen cell mass spectrometry with admission of molecular fluorine. The fluorination processes were controlled in the temperature range 500 ? 800 K at molecular fluorine pressure 10^?4 ? 10^?5 atm. Temperature, time of fluorination and fluorine pressure were varied during the investigation. It was found that variation of these parameters did not lead to the selective fluorination. It was shown that NiF₂(s) significantly influences the composition of the product mixture: a large amount of nickel difluoride in the system suppresses the fluorination reaction while the presence of a small amount promotes the selective fluorination. C₆₀Fi₁₈ (50% in the gas phase) was produced in our experiments under the following conditions: 20 h, 720 K, P(F₂) = 2 10^?4 atm in the prefluorinated (inner surface covered with NiF₂(s) layer) Ni-reactor. An important point of the study was verification of the thermodynamic equilibrium in the system. It was concluded that the equilibrium is not established in the system under study, and the fluorination is governed by kinetic factors.     

Crystal Structure of (H3O)6[(UO2)5(SeO4)8(H2O)5](H2O)5

Crystals of (H₃O)₆[(UO₂)₅(SeO₄)₈(H₂O)₅](H₂O)₅ were prepared from aqueous solutions by evaporation. The crystal structure [monoclinic system, space group P2₁/m, a = 13.835(2), b = 13.4374(16), c = 14.310(3) Å, β = 108.004(14)°, V = 2530.1(7) Å ³] was solved by the direct method and refined to R ₁ = 0.090 for 4409 reflections with |F _hkl ≥ 4σ|F _hkl |. The structure is based on [(UO₂)₅(SeO₄)₈(H₂O)₅]⁶⁻ layers arranged parallel to the (101) plane; these layers have a unique topological structure. The U(1)O₆(H₂O) and U(3)O₆(H₂O) linked through selenate groups form chains running along [ [`1]\bar 1 01] direction. The chains are combined in layers by U(2)O₆(H₂O) bipyramids. The layers are linked with each other by hydrogen bonds through the H₂O and H₃O⁺ groups located between the layers.     

Production of a high purity F radioactive beam

An efficient method for the production and post-acceleration of a pure ¹⁸F(T_1/2=109.8 min) radioactive beam has been developed. Large amounts of ¹⁸F are produced via the ¹⁸O(p,n)¹⁸F reaction using a 15.5 MeV proton beam on an ¹⁸O-enriched water target. After the chemical purification of the target content, the ¹⁸F activity is transferred into [¹⁸F]-fluoromethane. It is then transported to an ECR ion source, where after dissociation of the molecules, the fluorine atoms are ionized. Finally, the ¹⁸F²⁺ ions are accelerated to 14 MeV in a second cyclotron. The different steps in the production cycle and the characteristics of the final ¹⁸F beam are discussed.     

XRD and optical microscopic studies of Co(III) complexes containing 5-cyano-6-(4-pyridyl)-2-thiouracil, thymine and adenine bases

Multifunctional ligand 5-cyano-6-(-4-pyridyl)-2-thiouracil (L) was prepared and allowed to react withtrans [Co(en)₂Cl₂]⁺Cl^‡ resulting into [Co(en)₂LCl]²⁺.2Cl^- which upon further reaction with equimolar ratio of ligand [L] gave the complex [Co(en)₂L₂]³⁺.3Cl⁻. These metal complexes were then separately reacted with thymine and adenine bases. Complexes thus prepared after characterization by their elemental analysis, FAB mass and spectral (IR,¹ HNMR, UV-visible) data were studied for their powder X-ray diffraction and optical microscopic characteristics.