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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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).     

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.     

Solid-phase synthesis of deuterium- and tritium-labeled dopamine using carbon nanomaterials

Various procedures for preparing dopamine labeled with deuterium (²H) and tritium (³H) were considered. The labeled dopamine into which the hydrogen isotopes were introduced by solid-phase halogenation contained, on the average, 2.8 ²H (³H) atoms. The labeled dopamine prepared by solid-phase isotope exchange using nanodiamonds as support contained, on the average, 4.8 ²H (³H) atoms. The process was accompanied by the substrate deamination; as a result, the yield of the labeled analog was low (7–10%). Mass spectrometric analysis shows that the phenolic fragments formed by the dopamine deamination undergo dimerization.     

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%.     

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 Deoxyglucose and Its Derivative

Radiochemistry - Reaction of solid-phase catalytic heterogeneous isotope exchange of 2-deoxy-D-glucose and its derivative, O(6)-(4-bromothiophenyl)guanine-C8-β-D-glucose with tritium has been...     

Noncovalent Modification of Nanodiamonds with Tritium-Labeled Pantothenic Acid Derivatives

The efficiency of tritium labeling of salts of pantothenic (HO–R–COOH), hopantenic (HO–R–CH₂–COOH), and 4-D-phosphopantothenic [(HO)₂P(=O)–O–R–COOH] acids [R = CH₂C(CH₃)₂CHOH–CONH(CH₂)₂] with thermal activation of tritium at target temperatures of 77 and 295 K was studied. The phosphate group inhibits the isotope exchange. The tritium-labeled compounds were used for studying the adsorption of pantothenic acid derivatives from aqueous solutions and in the presence of 0.9% NaCl at 297 ± 3 K onto nanodiamonds prepared by detonation synthesis (NDs). Preparation of stable ND suspensions in advance enhances the ability of NDs to adsorb the compounds studied. The parameters of the equation describing the sorption isotherms at different ionic strengths of the solution were calculated. The strength of the adsorbate retention in contact with water, 0.9% NaCl solution, 0.01 M HCl solution, and 40 g L^?1 bovine serum albumin (BSA) solution was determined. The data obtained allow two mechanisms of the adsorbate retention on the ND surface to be considered: reversible adsorption due to ionic interactions and irreversible binding due to hydrophobic interactions. The strongly bound molecules undergo slow desorption in the presence of BSA. The revealed trends confirm high potential of NDs as a drug delivery platform.

     

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.     

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.     

Use of methyl <Emphasis Type="Italic">p</Emphasis>-toluenesulfonate labeled with hydrogen isotopes as a donor of methyl group

Methyl p-toluenesulfonates TosOCH₂ ³H and TosOCH₂ ²H containing, on the average, 0.5 atom of hydrogen isotope per molecule were prepared by catalytic dehalogenation of bromomethyl p-toluenesulfonate TosOCH₂Br with tritium and deuterium. Mass-spectrometric analysis showed that the label is fully localized in the methoxy group. The use of this reagent allowed preparation of isotopically labeled biologically active compounds containing the fragments -OCH₃, -COOCH₃, -SCH₃, etc.     

Thermal dissociation of the complex BF<Subscript>3</Subscript>·D and boron isotope separation in the system BF<Subscript>3</Subscript>-BF<Subscript>3</Subscript>·CH<Subscript>3</Subscript>NO<Subscript>2</Subscript>

Thermal flow reversal and efficiency of interphase isotope exchange in the course of multiplication of the single effect of boron isotope separation in the two-phase system gaseous BF₃-liquid complex of BF₃ with nitromethane in an isotope exchange column at atmospheric pressure and 293 K was studied. The completeness of flow reversal is acceptable for concentrating ¹⁰B. Approximately 19 at. % difference in the concentrations of the isotope ¹⁰B was attained on an experimental installation with a packed mass-exchange column 11 mm in diameter at a packing bed height of 148 cm and spiral-prismatic packing with an element size of 1.25 × 1.25 × 0.2 mm. The degree of separation was K = 3.5, and HETP was in the range from 5.2 ± 0.8 to 8.0 ± 1.0 cm, suggesting high efficiency of the mass exchange.     

Solid-phase catalytic reactions of tritium with carbohydrates: 4. Mechanism of isomerization of <Emphasis Type="Italic">D</Emphasis>-glucose in the course of solid-phase catalytic hydrogenation with tritium

The influence exerted on solid-phase catalytic hydrogenation (SCH) of D-glucose with tritium by the temperature varied in the range 90–140°C, platinum group catalysts, solid phase composition, reaction time, and surface area of the support was examined. Fructose and mannose were identified in the reaction products along with labeled glucose. The mechanism of the isomerization of glucose into fructose and mannose in the solid phase under the action of hydrogen spillover was suggested. The glucose isomerization occurs by a complex mechanism analogous to acid-catalyzed keto-enol tautomerization of epimeric sugars in solution, and the active species in SCH of D-glucose with tritium is spillover hydrogen in the form of proton.