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The experimental conditions which control the exchange from deuterium or tritium gas into the C-1 proton position of glucose in aqueous solution have been studied in detail, with a view to determining the factors which maximize exchange into glucose, but minimize exchange into the solvent water. The favoured conditions for producing glucose with close to 100% isotope labelling in the C-1 position, and with negligible formation of labelled byproducts, were a reaction time of 6 to 8 hours, a temperature of 60°C, and a pH of 7 or higher. Pd/BaSO 4 was the preferred catalyst and slow pre-addition of the deuterium or tritium gas to the catalyst bed was essential to maximize the subsequent isotope exchange into the substrate.

Platinum-loaded microporous aluminophosphate molecular sieves (Pt-AlPO4-5) were synthesized and studied as catalysts for promoting tritium isotope labelling by exchange between tritium gas and aromatic, heteroaromatic and aliphatic hydrocarbons. The presence of the Pt metal considerably enhanced the activation of the tritium gas. Detailed isotope orientation patterns, as determined by 3H nmr spectroscopy, showed that the AlPO4-5 component of the catalyst dominated the exchange reactions, but some influence of the Pt metal was apparent with some substrates.

A synthesis of [3H]R- and [3H]S-4-amino-3-phenylbutanoic acid ([3H]R- and [3H]S-β-phenylGABA) from the unsaturated intermediate by catalytic hydrogenation using tritium gas in the presence of palladium on charcoal is reported. The [3H]R- and [3H]S-diastereoisomers of pantolactone ester of β-phenylGABA were separated by HPLC.

The first application of tritium NMR spectroscopy to the direct observation of proton-exchange kinetics is described; this technique allows the study of milligram amounts of substrates and for substrates with multiple exchangeable positions. The examples include benzene and the ring and methyl positions of p-xylene reacting with cesium cyclohexylamide in cyclohexylamine, and the enolate positions of cyclohexanone and methyl 7,12-dihydroxy-3-ketocholan-24-oate reacting with heptafluorobutyric acid in dioxane.

A wide range of simple organic substrates has been successfully tritium labelled using reduced platinum oxide as catalyst. Exchange conditions involved reaction temperatures in the range 60–150°C, and reaction times of 3–7 days. The isotope sources for the reactions were tritium gas and tritiated water. Analysis of the labelled products was accomplished by radio‐glc and by H NMR spectroscopy. The specific activities ranged up to 1100 mCi/mL, and most of the labelled products showed high radiochemical purity. The regioselectivity of tritium incorporation, as obtained from H NMR studies, supports currently accepted theories for mechanisms of platinum‐catalyzed hydrogen isotope exchange. The results also show remarkable consistency for a heterogeneous system under widely varying reaction conditions.

Levamisole (LEV) is a widely used anti-parasitic agent. In order to characterise the biochemical pharmacology of LEV in parasitic nematodes, [3H]LEV and a more active analogue [3H]m-aminolevamisole (MAL) have been prepared. Labelling was accomplished by tritiated water exchange of MAL under acid conditions. Multiple site labelling was achieved in the positions ortho and para to the amino group of MAL. Tritiation of MAL HCl in [3H]2O was achieved at 103°C for 23 h. Crude [3H]MAL was diazotised (hydrochloric acid and sodium nitrite) and deaminated (hypophosphorous acid) to effect the synthesis of [3H]LEV. Products of both reactions were purified by preparative h.p.l.c. and characterised by h.p.l.c., t.l.c. and mass spectrometry. (Radiochemical yield was about 15% and purity >90%.) Specific activities of 39 Ci/mmol for [3H]MAL and 37 Ci/mmol for [3H]LEV were obtained.

The tritiation of a range of low molecular weight alkanes and alkenes has been investigated by self-radiation induced exchange with HTO at room temperature and 115°. By comparison with the Wilzbach T2 gas exposure procedure, the HTO method yields less byproducts and radiochemical purification of the parent compound is facilitated. With alkenes, saturation of the double bond is a competing process in the HTO procedure, however the significance of this side reaction decreases with increasing temperature of exchange. The HTO technique is shown to be suitable for tritiating a wide range of hydrocarbons to medium levels of specific activity.

A method for the synthesis and purification of mebendazole specifically labelled with tritium in the 4′ position is described.

Boron tribromide has been assessed as a catalyst for rapid tritium labeling of organic compounds using tritiated water under mild conditions. Alkyl and halogen substituted aromatics labeled rapidly, the labeling being most pronounced in the ortho and para positions. Compounds containing electrophilic deactivating groups were found to be difficult to label. Very little byproduct formation was observed.

Adaptation du second detecteur d'ionisation de flamme d'un chromatographe gazeux a deux detecteurs, pour en faire une chambre d'ionisation

A practical synthesis of [14-3H]dibenz[a,j]acridine and [7-3H]dibenz[a,h]acridine is reported from the parent hydrocarbon by catalytic exchange with tritium gas in the presence of palladium on calcium carbonate. Analogous regiospecific labelling with deuterium was also affected. In addition [14-14C]dibenz[a,j]acridine was prepared from [14C]paraformaldehyde.

Benzimidazole carbamates (BZCs) act as inhibitors of the tubulin-microtubule equilibria in eukaryotic organisms. Recently drug resistance to this class of compounds in helminth parasites has been shown to be due to a reduced ability of resistant tubulin to bind BZCs. In order to quantitate the nature of the tubulin-BZC interaction a general method for the specific tritium labelling of BZCs has been developed. The BZCs: mebendazole, oxfendazole, parbendazole, oxibendazole, albendazole and fenbendazole were labelled by catalytic exchange using palladium on calcium carbonate in pure dioxane at 60°C under tritium gas. The position of label incorporation for tritiated albendazole was determined by tritium-NMR as the 4-position of benzimidazole nucleus. The yields for individual BZCs varied from 8 to 68% for a range of specific activity of 0.44 to 13.4 Ci/mmole.

The stereochemistry of the tritiation of L-chiro-inositol, myo-inositol and hexa-O-methyl-L-chiro-inositol by self-radiation induced exchange with tritiated water of high specific activity has been investigated. Predominance of configurational retention was found to accompany tritium labelling in the two inositols, while substantial configurational inversion occurred in the hexa-O-methyl derivative. Tritiation occurred predominantly at C 1 in L-chiro-inositol, with slight inversion at this position alone accompanying the labelling. Comparison with Wilzbach T2 gas exposure results indicates the HTO method yields less by-products, myo-inositol having a radiochemical purity of 97%.

Tritium labelled hexamethyldisiloxane is a suitable material for the internal referencing of 3H NMR spectra. Such a referencing procedure is necessary where the instrument is not capable of scanning 1H resonance under identical experimental conditions. Hexamethyldisiloxane may be tritiated to high activity (typically 1 Ci ml−1) by Raney nickel catalysed exchange with elemental tritium in a simple one-step procedure. A variety of heterogeneous catalysts are shown to be inactive in the common labelling method involving exchange with tritiated water.

The principle of using small amounts of high activity water in an otherwise water-sensitive catalytic system has previously been employed with Lewis acid labeling catalysts. The advantages of such procedures include the relative simplicity of handling tritiated water and its low cost compared with alternatives such as tritium gas and tritiated benzene. No vacuum techniques are necessary, and the activity of the product is limited only by the specific activity of the small aliquot of HTO used as isotope source. The reactants, organic (0.1 g), zeolite (25 mg), and tritiated water (5 ..mu..L, 40 mCi/mL) were sealed in a glass ampule and heated to 175/sup 0/C for the desired reaction time. Products were analyzed by radiogas chromatography and /sup 3/H NMR spectroscopy. The results show that the procedure represents a highly efficient method of tritiation of most aromatic compounds. Since the molar ratio of organic compound to water was high, equilibrium represents virtually 100% incorporation of the tritium utilized in the experiment.

The orientation of plantium-metal catalysed exchanged between tritiated water and pyridine, the picolines, 2,6-lutidine, and the quinolines has been carefully studied 3H n.m.r. Exchange at 130 °C occurs preferentially at a position adjacent to the nitrogen atom unless a methyl substituent on C-2 hinders exchange, when a position remote from the methyl substituent is preferred as in alkylaromatic exchange. The results are interpreted in terms of previously proposed π-complex exchange mechanisms.

Microporous aluminophosphate (ALPO) catalysts are shown to have high activity and unique specificity for exchange between elemental tritium gas and both aromatic and branched aliphatic compounds, suggesting their applicability as catalysts in a range of other reactions.

Ruthenium metal prepared by NaBH4-reduction of RuO2 possesses unique activity in consistently catalysing hydrogen isotope exchange between organosilanes and C6D6., exchange occurring readily in alkul and aryl positions, particularly in trisubstituted silanes; a modification of the technique can also be used for the tritium labelling of these silanes.

The stereochemistry of the tritiation of L-chiro-inositol, myo-inositol and hexa-O-methyl-L-chiro-inositol by self-radiation induced exchange with tritiated water of high specific activity has been investigated. Predominance of configurational retention was found to accompany tritium labelling in the two inositols, while substantial configurational inversion occurred in the hexa-O-methyl derivative. Tritiation occurred predominantly at C 1 in L-chiro-inositol, with slight inversion at this position alone accompanying the labelling. Comparison with Wilzbach T2 gas exposure results indicates the HTO method yields less by-products, myo-inositol having a radiochemical purity of 97%.