Synthesis of tritium-labeled Ganciclovir

The influence of temperature on the solid-phase isotope exchange of Ganciclovir with tritium was studied. Synthesis conditions were found, and tritium-labeled Ganciclovir with the molar radioactivity of 25 Ci mmol⁻¹ (0.925 PBq mol⁻¹) and purity higher than 98% was prepared.     

Hydrogen isotope labeling of α-hederin and a mass-spectrometric study of deuterium distribution

Deuterium-labeled α-hederin was prepared. Under the chosen conditions, 0.45–0.50 deuterium atom, on the average, is incorporated in the α-hederin molecule. The deuterium distribution was determined by mass spectrometry. The ratio between the deuterium contents in the disaccharide residue of the α-hederin molecule and in its steroid moiety is about 3: 1. The latter fact indicates that the double bond in the streoid moiety of α-hederin in the case of using a solid-phase labeling procedue is inaccessible to activated species of hydrogen isotopes. When performing isotope exchange in a gaseous tritium atmosphere, the molar radioactivity of the preparation reached 10 Ci mmol⁻¹.     

Isotope Exchange of Azidothymidine with Tritium

The following modes of isotope exchange of azidothymidine (3'-azido-3'-deoxythymidine) with tritium were studied: solid- and liquid-phase isotope exchange with gaseous tritium and isotope exchange in solution with tritium water. Catalytic reactions of azidothymidine with gaseous tritium in solution result in virtually complete reduction of the azido group to amino group. This reduction also occurs in the course of solid-phase catalytic hydrogenation; the yield of 3'-amino-3'-deoxythymidine ranges from 20 to 70%. The molar radioactivity of tritium-labeled azidothymidine prepared by solid-phase catalytic isotope exchange with gaseous tritium and by isotope exchange in solution with tritium water does not exceed 0.5 Ci mmol^{- 1}.     

Introduction of hydrogen isotopes into Win 55212 and CP 55940, selective agonists of cannabinoid receptors

Selective agonists of cannabinoid receptors Win 55 212 and CP 55 940, labeled with hydrogen isotopes, were prepared. The content of isotopomers in deuterium-labeled Win 55 212 and CP 55 940, and also the deuterium distribution in fragments of the [²H]Win 55212 molecule were determined by mass spectrometry. [³H]Win 55 212 and [³H]CP 55 940 with molar radioactivities of 55 and 70 Ci mmol⁻¹, respectively, were prepared by the reaction with gaseous tritium. The efficiency of isotope exchange with activated hydrogen species under the conditions of primary and secondary hydrogen spillover is discussed.     

Synthesis of High-Molar-Activity Tritium-Labeled Biologically Active Compounds Containing Aromatic and Heterocyclic Fragments

Procedures are examined for tritium labeling of biologically active compounds. By isotope exchange with tritium water, it is possible to prepare products with the molar radioactivity of about 1 PBq mol^{- 1}. The molar radioactivities of compounds prepared by solid-phase isotope exchange with gaseous tritium at 180-220°C reached 5-6 PBq mol^{- 1}. The degree of labeling varied by a factor of more than 100 depending on the physicochemical properties of the substrate. Selective hydrogenation of a heterocyclic fragment of an organic compound, leaving intact the aromatic fragment, was performed for the first time by solid-phase tritiation.     

Solid-Phase Catalytic Hydrogenation of Uracil with Tritium: Synthesis of Tritium-Labeled β-Alanine

Solid-phase catalytic hydrogenation of uracil with gaseous tritium was studied. Isotope exchange of protons at C⁵ and C⁶ is accompanied by hydrogenation of the 5,6-double bond in the pyrimidine core; as a result, a mixture of tritium-labeled uracil and 5,6-dihydrouracil is formed. The influence of the reaction temperature and time on the yield and molar radioactivity of these compounds was examined. The best conditions for cleavage of 5,6-dihydrouracil into -alanine were found. [5,6-³H₂]Uracil (49 Ci mmol^{- 1}), [5,5,6,6-³H₄]5,6-dihydrouracil (100 Ci mmol^{- 1}), and [2,2,3,3-³H₄]-alanine (100 Ci mmol^{- 1}) were prepared.     

Optimization of Conditions for Tritium Labeling of Organic Compounds by Isotope Exchange with Tritium Water,Based on the Concepts of Reactions on the Catalyst Surface

To reveal factors affecting the tritium labeling by isotope exchange with tritium water and to elucidate the reaction mechanism, the concepts of processes involved in heterogeneous catalysis were considered. Conditions were optimized for tritium labeling of deltamethrin, pargiline, trichostatin, ciprofloxacin, and 1,3-O-dibenzylglycerol. Samples with the molar radioactivity of 9.3, 0.5, 1.8, 35.1, and 57.3 Ci mmol⁻¹, respectively, were prepared.__________Translated from Radiokhimiya, Vol. 47, No. 4, 2005, pp. 368–373.Original Russian Text Copyright © 2005 by Shevchenko, Nagaev, Myasoedov.     

Specific features of deuterium and tritium labeling of SB258585

Samples of SB258 585 labeled with hydrogen isotopes were synthesized. [²H]SB258 585 containing one ²H atom per molecule and [³H]SB258585 with the molar radioactivity of 15 Ci mmol^?1 were obtained in preparative amounts. From 0.18 to 1.5 ²H atoms were incorporated, on the average, into an SB 258 585 molecule depending on the reaction conditions. The isotope exchange efficiency strongly depends not only on the catalyst-substrate ratio and on the reaction temperature, but also on processes occurring on the support surface. The isotope effects strongly influence the degree of deuterium or tritium incorporation into the samples in cases when the organic compound largely decomposes in the course of the reaction.     

Synthesis of [3H]Sulfobromophthalein and Related Problems of Tritium Labeling by Solid-Phase Isotope Exchange

Tritium-labeled sulfobromophthalein with a molar radioactivity of 0.5-0.6 PBq mol^-1 was prepared. Various aspects of tritium labeling of organic compounds by solid-phase catalytic isotope exchange are considered. A number of arguments are given in favor of the hypothesis that the degree of isotope exchange mainly depends on the efficiency of tritium spillover in the bulk of the organic substances applied onto the catalyst surface. At present, it can be considered as a reliably proved fact that at temperatures up to 180-200°C the solid-phase isotope exchange mainly occurs via reaction with tritium cations. Apparently, the contribution of the reactions with atomic tritium to labeling is significant only if there is no spillover of tritium cations to the bulk of the organic compound and the substrate withstands heating to 280-300°C.     

Hydrogen isotope labeling of PTC124

PCT124 labeled with hydrogen isotopes was prepared. For efficient isotope labeling of this compound, the reaction should be performed under severe conditions. With additional supports, the isotope exchange could be performed at 260–270°C. Under these conditions, the labeled compound with the molar radio-activity of 6.5 Ci mmol^-1 was prepared. The deuterium distribution in fragments of the [²H]PTC124 molecule was determined by mass spectrometry. Based on the data obtained, possible mechanism of incorporation of hydrogen isotopes into PTC124 was considered.     

Synthesis of tritium-labeled 2′,3′-dideoxy-2′,3′-didehydrothymidine and 3′-azidothymidine-5′-phosphamide

Tritium-labeled 2′,3′-dideoxy-2′,3′-didehydrothymidine and 3′-azidothymidine-5′-phosphamide were prepared by isotope exchange with highly enriched tritium water. Tritium water was prepared by oxidation of high-percentage tritium on PdO. The isotope exchange was performed at 100°C in the dioxane-triethylamine mixed solvent (9: 1 by volume). The molar radioactivities (GBq mol^?1) and yields (%) of the products were, respectively, as follows: 2′,3′-dideoxy-2′,3′-didehydrothymidine, 82, 44; 3′-azidothymidine-5′-phosphamide, 200, 71.     

Isotope exchange reactions of trans-zeatin with tritium

Isotope exchange of trans-zeatin with high-activity tritium water and with gaseous tritium in solution, and also the solid-phase catalytic hydrogenation of this compound were studied. The isotope exchange of trans-zeatin with gaseous tritium, both in solution and without a solvent at 160°C and higher temperatures, is accompanied by virtually complete hydrogenation of the starting compound with the formation of tritium-labeled dihydrozeatin. The isotope exchange of trans-zeatin with high-activity tritium water allows preparation of tritium-labeled zeatin in 67% yield and molar activity of 0.68 PBq mol^?1. When the solid-phase isotope exchange is performed at 150–155°C, the reaction products contain tritium-labeled trans-zeatin along with the hydrogenation product, dihydrozeatin. At 170°C, the only reaction product is dihydrozeatin. Thus, the selectivity of tritium labeling varies with the temperature of solid-phase catalytic hydrogenation. Below 160°C, the solid-phase reaction can be performed selectively, i.e., with the preservation of the double bond in the starting trans-zeatin. Above 170°C, the selectivity is lost, and the compound is virtually fully hydrogenated to dihydrozeatin.     

Nonequilibrium processes in reactions of hot tritium atoms with cooled solid targets. Influence of the atomizer temperature on formation of labeled substances

A system consisting of a cold target and “hot” atoms generated by dissociation of tritium on a tungsten wire was studied with the aim to determine conditions for preparing tritium-labeled organic compounds with the maximal radiochemical yield. The influence of the atomizer temperature on the result of the reaction of tritium atoms with amino acids and tetraalkylammonium bromides was studied; homological series of the substrates were examined with the aim to evaluate the contributions of functional groups and hydrocarbon tail to the processes occurring in the target. The dependence of the yield of the labeled parent compound on the atomizer temperature varied in the range 1600–2000 K was determined. The rates of decarboxylation and deamination sharply grew with increasing temperature of the tungsten wire. The highest yield of labeled amino acids was attained at an atomizer temperature of 1800–1900 K, and at higher temperature their yield decreased. The difference between the activation energies of the elimination of the carboxy and amino groups and of the isotope exchange of hydrogen for tritium in the C-H bond appeared to be 93 and 59 kJ mol^?1, respectively. For alkyltrimethylammonium bromides with the alkyl radicals C₁₂H₂₅, C₁₄H₂₉, and C₁₆H₃₃, the yield of the labeled parent compound reached 80–90% and was virtually independent of the atomizer temperature. The capability of tritium atoms to penetrate into the targets was evaluated. For the exponential model of the attenuation of the flow of tritium atoms inside the target, the attenuation factor for freeze-dried amino acids and alkyltrimethylammonium bromides as targets was 1.8 nm^?1.     

Solid-Phase Catalytic Hydrogenation of Orotic Acid and 5-Bromouracil with Tritium on a Copper Catalyst

The performance of a copper-based catalyst in solid-phase catalytic hydrogenation of orotic acid and 5-bromouracil with gaseous tritium was studied. Hydrogen isotope exchange in the carboxy group of orotic acid was combined with decarboxylation in a one-pot process. The catalyst performance was judged from the molar radioactivity of [6-³H]uracil and [5-³H]uracil formed by catalytic hydrogenation with gaseous tritium of orotic acid and 5-bromouracil, respectively. In solid-phase catalytic dehalogenation, the performance of the copper-based catalyst is comparable with that of the palladium catalyst, but this level is attained at a higher temperature. To evaluate the performance of the copper catalyst in isotope exchange reactions, additional studies with a wider range of substrates are required.     

Surface re-equilibration kinetics of nonstoichiometric oxides

The sorption of small oxygen doses on initially equilibrated oxide surfaces is accompanied by changes in the work function with time, involving initial charging (due to chemical sorption of oxygen), passing through a maximum, and a final discharging. The final discharging is assumed to be rate controlled by chemical diffusion through the oxide surface layer. The kinetics of the changes in work function accompanying the re-equilibration process were measured for NiO, lithium-doped NiO (0.13 at.% Li₂O) CoO, and Co₃O₄. The rate constants of the discharging processes were determined as a function of temperature giving the following activation energy values, respectively: 29 kcal mol⁻¹ (300 to 425° C), 1 kcal mol⁻¹ (200 to 300° C); 17.8 kcal mol⁻¹ (300 to 400° C); 18.3 kcal mol⁻¹ (175 to 350° C); 19.9 kcal mol⁻¹ (225 to 350° C). The kinetics of sorption of oxygen were measured for undoped NiO in the temperature range 200 to 400° C, giving a change in activation energy at 300° C from 33.9 kcal mol⁻¹ above, and 11 kcal mol⁻¹ below the temperature. It was concluded that above 300° C the NiO lattice becomes sufficiently mobile to enable ionic transport to take place. This temperature corresponds well to the temperature at which several other properties of NiO also change. The work function data obtained for an NiO-Li₂O solid solution suggest a different mechanism of lithium incorporation into the bulk and the surface layer of NiO. The kinetic data for both CoO and Co₃O₄ indicate that the chemical diffusivity of the boundary layer of these oxides does not depend on the structure of the crystalline bulk. The presented results indicate that the work function method is suitable for studying the transport properties of the boundary layer of non-stoichiometric oxides.     

Thermal Diffusivity and Heat of Formation of Harzburgite and Its Major Constituent Minerals

The thermal diffusivity, D, and its temperature dependence of Oman harzburgite rock and its major mineral olivine have been evaluated from the basic properties such as seismic velocities, density, and Debye temperature. The Arrhenius-type temperature dependence of the diffusivity was utilized to evaluate the heat of formation, ΔH _D. The diffusivity values, 1.80mm² · s⁻¹ and 2.1mm² · s⁻¹ obtained at room temperature for harzburgite and olivine, respectively, are consistent with available data. The diffusivity values for Oman harzburgite are overestimated by an amount of 0.27mm² · s⁻¹ relative to those of PNG harzburgite. The ΔH _D value (−2.40 kJ · mol⁻¹) for harzburgite rock of the Oman ophiolite suite is comparable with that (−2.90 kJ · mol⁻¹) of the harzburgite rock of Papua New Guinea. The disagreements in the thermal diffusivity and heat of formation values may be partly due to ignoring the effect of pyroxene in Oman harzburgite.     

Measurement of Gibbs energies of formation of CoF2 and MnF2 using a new composite dispersed solid electrolyte

Gibbs energies of formation of CoF₂ and MnF₂ have been measured in the temperature range from 700 to 1100 K using Al₂O₃-dispersed CaF₂ solid electrolyte and Ni+NiF₂ as the reference electrode. The dispersed solid electrolyte has higher conductivity than pure CaF₂ thus permitting accurate measurements at lower temperatures. However, to prevent reaction between Al₂O₃ in the solid electrolyte and NiF₂ (or CoF₂) at the electrode, the dispersed solid electrolyte was coated with pure CaF₂, thus creating a composite structure. The free energies of formation of CoF₂ and MnF₂ are (± 1700) J mol⁻¹; {fx37-1} The third law analysis gives the enthalpy of formation of solid CoF₂ as ΔH° (298·15 K) = −672·69 (± 0·1) kJ mol⁻¹, which compares with a value of −671·5 (± 4) kJ mol⁻¹ given in Janaf tables. For solid MnF₂, ΔH°(298·15 K) = − 854·97 (± 0·13) kJ mol⁻¹, which is significantly different from a value of −803·3 kJ mol⁻¹ given in the compilation by Barinet al.     

Kinetic studies of water uptake and loss in glass-ionomer cements

The water sorption and desorption behaviour of three commercial glass-ionomer cements used in clinical dentistry have been studied in detail. Cured specimens of each material were found to show slight but variable water uptake in high humidity conditions, but steady loss in desiccating ones. This water loss was found to follow Fick’s law for the first 4–5 h. Diffusion coefficients at 22 °C were: Chemflex 1.34 × 10⁻⁶ cm² s⁻¹, Fuji IX 5.87 × 10⁻⁷ cm² s⁻¹, Aquacem 3.08 × 10⁻⁶ cm² s⁻¹. At 7 °C they were: Chemflex 8.90 × 10⁻⁷ cm² s⁻¹, Fuji IX 5.04 × 10⁻⁷ cm² s⁻¹, Aquacem 2.88 × 10⁻⁶ cm² s⁻¹. Activation energies for water loss were determined from the Arrhenius equation and were found to be Chemflex 161.8 J mol⁻¹, Fuji IX 101.3 J mol⁻¹, Aquacem 47.1 J mol⁻¹. Such low values show that water transport requires less energy in these cements than in resin-modified glass-ionomers. Fick’s law plots were found not to pass through the origin. This implies that, in each case, there is a small water loss that does not involve diffusion. This was concluded to be water at the surface of the specimens, and was termed “superficial water”. As such, it represents a fraction of the previously identified unbound (loose) water. Superficial water levels were: Chemflex 0.56%, Fuji IX 0.23%, Aquacem 0.87%. Equilibrium mass loss values were shown to be unaffected by temperature, and allowed ratios of bound:unbound water to be determined for all three cements. These showed wide variation, ranging from 1:5.26 for Chemflex to 1:1.25 for Fuji IX.     

Oxygen isotope shifts of the Raman modes of YBa2Cu3O7−x

Raman scattering experiments have been carried out on sintered pellets of YBa₂Cu₃ ¹⁶O_7−x and YBa₂Cu₃ ¹⁸O_7−x obtained both by gas exchange and by growth with substituted oxides. The frequencies of the modes at 340, 435 and 502 cm⁻¹, which involve motion of the oxygen atoms and which shift significantly upon oxygen isotope substitution, have been measured for several sets of samples. The measured frequency shifts indicate that the isotope exchange on the O(2) and O(3) sites is more complete than the exchange on the O(4) site. The 502 cm⁻¹ line of the¹⁸O samples is observed to be broadened and this is attributed to¹⁸O-¹⁶O disorder on the O(4) sites. The results are discussed with reference to previous measurements of site activation energies and models for the exchange mechanism.     

Investigation on Phase Transitions and Thermodynamic Properties of 1-Dodecylamine Hydrochloride (C<Subscript>12</Subscript>H<Subscript>25</Subscript>NH<Subscript>3</Subscript>Cl)(s) by an Improved Adiabatic Calorimeter

1-Dodecylamine hydrochloride was synthesized by the solvent-thermal method. The structure and composition of the compound were characterized by chemical and elemental analyses, the X-ray powder diffraction technique, and X-ray crystallography. The main structure and performance of an improved automated adiabatic calorimeter are described. Low-temperature heat capacities of the title compound are measured by the new adiabatic calorimeter over the temperature range from 78 K to 397 K. Two solid-to-solid phase transitions have been observed at the peak temperatures of (330.78 ± 0.43) K and (345.09 ± 0.16) K. The molar enthalpies of the two phase transitions of the substance were determined to be (25.718 ± 0.082) kJ · mol⁻¹ and (5.049 ± 0.055) kJ · mol⁻¹, and their corresponding molar entropies were calculated as (77.752 ± 0.250) J · mol⁻¹ · K⁻¹ and (14.632 ± 0.159) J · mol⁻¹ · K⁻¹, respectively, based on the analysis of heat–capacity curves. Experimental values of heat capacities for the title compound have been fitted to two polynomial equations. In addition, two solid-to-solid phase transitions and a melting process of C₁₂H₂₅NH₃Cl(s) have been verified by differential scanning calorimetry.