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.     

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.     

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}.     

Tritium Sorption by Modified Natural Aluminosilicates

In connection with problems of interaction of tritium-containing underground waters with clay geological barriers and tritium water treatment, the sorption of tritium by natural and synthetic clays modified with organic compounds was studied. The mechanism of tritium sorption by aluminosilicates, involving the isotope exchange of hydrogen atoms in organic and inorganic compounds, was proposed. Modification of clays with organic compounds shows promise as a way to improve the sorption capacity of clays with respect to tritium.     

Effect of Processes Occurring in the Presence of Metal Catalysts on the Main Characteristics of the Hydrogen Isotope Labeled Organic Compounds Obtained

Radiochemistry - The main deuterium and tritium sources used for preparing hydrogen isotope labeled compounds are presented. The mechanisms of hydrogenation and isotope exchange in organic...     

Efficiency of isotope exchange between sodium 4-phenylbenzoate and activated tritium

The efficiency of the protium–tritium isotope exchange in the sodium 4-phenylbenzoate (PBNa) molecule on activating the reaction on a tungsten filament at 1940 K (target temperature 77 and 295 K) and on heating the substrate supported on 5% Pd/C in the presence of gaseous tritium is compared. It is shown that the reaction mechanism is laregly determined by the properties of the material on which this reaction occurs and not only by the method of generation of activated tritium species. In the reaction of tritium atom with PBNa deposited on glass walls of the reaction vessel, the isotope substitution of tritium for protium occurred by the radical mechanism, leading to the formation of [³H]PBNa and hydrogenation products. It is assumed that the spillover of tritium atom over the support (carbon) surface is accompanied by polarization of the electronic shell and formation of the cluster (^{3 +})(\(\bar e\)), which leads to changes in the composition of the reaction products. The combined treatment of PBNa on 5% Pd/C allows estimation of the concentration of clusters on the carbon surface, which reaches 10.9 particles per 100 nm² (9.2 nm² per cluster).     

Heterogeneous Catalytic Synthesis of Organic Compounds Labeled with Hydrogen Isotopes without Using Solvents

Solid-phase procedures for hydrogenolysis, hydrogenation, and isotope exchange are described. The possibilities of the solid-phase method for deuterium or tritium labeling of organic compounds are demonstrated. The influence of the reaction conditions on the yield of the labeled products and on the degree of hydrogen isotope incorporation into them is considered. An attempt is made to rationalize the data obtained by processes occurring in the hydrogen isotope–catalyst–support–substrate system.     

Selective Tritium Labeling by a Solid-Phase Procedure

Ways were considered how substrates that contain such reactive centers as halogen atoms and double bonds can be labeled with tritium by solid-phase isotope exchange. The feasibility was demonstrated for tritium labeling by selective solid-phase dehalogenation, hydrogenation, and isotope exchange. Highly labeled vitamin K₁, dihydrofusicoccin, and thyroxine and its derivatives were prepared.     

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.     

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 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.     

Tritium labeling of bioorganic compounds by isotope exchange

Procedures for preparing labeled compounds by liquid- and solid-phase methods using gaseous tritium and by isotope exchange with tritium water are considered as different manifestations of a common complex of processes occurring in the presence of tritium, a substrate, and a catalyst. The studies performed allow purposeful optimization of the conditions of tritium labeling of practically any biologically active substance, which makes possible more detailed investigation of the functioning of living objects.     

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.     

Effect of Technetium on the Efficiency of Solid-Phase Isotope Exchange

Tritium-labeled hexadecane, glycine, and -aminocaproic acid were prepared in the presence of supported palladium catalysts (straight and impregnated with technetium). The degree of isotope exchange is strongly affected by the reaction conditions. In isotope exchange of gaseous tritium with hexadecane, the degree of exchange obtained with the technetium-impregnated catalysts exceeds that obtained with the monometallic catalysts. The nature of the synergism is discussed.     

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.     

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.     

Synthesis of tritium-labeled 5-fluorouracil and 5-fluorocytosine

The effect of various catalysts and temperature on the solid-phase isotope exchange of 5-fluorouracil and 5-fluorocytosine with tritium was studied. The isotope exchange yielding the desired compounds is accompanied by dehalogenation and hydrogenation of the 5,6-double bond of the pyrimidine ring. Performing the reaction at a temperature below 160°C allowed the process to be carried out selectively, i.e., with the preservation of the functional groups and double bond in the starting compound. The yields of various products formed in the reactions of tritium with the above compounds were estimated. Synthesis conditions were found, and tritium-labeled 5-fluorouracil and 5-fluorocytosine were prepared with the molar radioactivity of 0.45 Ci mmol⁻¹ (16.7 TBq mol⁻¹) and 4.4 Ci mmol⁻¹ (0.16 PBq mol⁻¹), respectively, and with the purity exceeding 98%.     

Solid-phase catalytic reactions of tritium with carbohydrates: 5. Mechanism of isomerization of epimeric disaccharides in the course of solid-phase catalytic hydrogenation with tritium

The influence exerted on the solid-phase catalytic hydrogenation of lactulose with tritium by temperature in the range 130–160°C, platinum group catalysts, solid phase composition, and support surface area was studied. Lactose was identified in the reaction products along with labeled lactulose. The mechanism of isomerization of sugars in the solid phase under the action of hydrogen spillover was suggested. Isomerization of sugars occurs by a complex mechanism similar to acid-catalyzed keto-enol tautomerization of epimeric sugars in solution, and the active species in SCH of sugars with tritium is spillover hydrogen in the form of proton.     

A method for the extraction of ammonium from freshwaters for nitrogen isotope analysis

The measurement of delta15N values of inorganic nitrogen species is an important analytical tool to trace nitrogen species in order to understand nitrogen cycling in aquatic systems. Nitrogen isotope analysis of freshwater ammonium has, however, been hindered by the lack of a simple and reliable technique to measure delta15N values at natural abundance levels. We present a simple and rapid method to concentrate ammonium from freshwater samples for on-line N-isotope ratio determination. Ammonium is collected by adsorption on N-free cation exchange resins. The dried N-loaded exchange resin is then directly combusted to produce N2 gas for subsequent delta15N analysis. The method was evaluated with simulated freshwater solutions containing varying amounts of standard NH4+-N (delta15N = 2.1 per thousand) and potentially interfering inorganic and organic compounds. In general, the cation exchange resin method gives accurate and reproducible delta15N values (sigma1 < 0.3 per thousand; n = 10). Because of adsorption interference, high concentrations of cations in solution may cause ammonium loss but do not result in measurable isotope fractionation. Replicate extractions of the ammonium standard added to water collected from four Swiss lakes demonstrate the good performance of this method when applied to low ionic strength natural water samples with modest concentrations of dissolved organic nitrogen.     

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.