Tritium discovery

The production of tritium-labelled organic compounds was enormously facilitated by K. E. Wilz-bach s discovery in 1956 that tritium could be introduced merely by storing a compound under tritium gas for a few days or weeks the radiation induces exchange reactions between the hydrogen atoms in the compound and the tritium gas. The excess of gas is recovered for further use and the tritiated compound is purified chro-matographically. Another widely used method of... 

The incorporation of 14C into compounds at a suitable site often requires extensive and complicated syntheses, and thus a relatively long time. This usually means that 14C-labeled compounds are unsuitable for studies to be carried out during discovery. There are however, very rapid methods for incorporating 3 H into compounds. The newer methods, generally involving metal-catalyzed exchange reactions [15-18], in our experience, mean that suitable labels can often be prepared in 2 or 3 weeks. These time scales make the approach viable for discovery support. Additionally, and importantly, these methods can lead to specific incorporation of tritium. 

The tritium work at Surrey has been generously funded over many years by EPSRC (previously SERC and at the beginning, SRC), the EU, NATO and the chemical industry. The task of writing the current chapter was undertaken as part of the EU sponsored DIO COST Program (Innovative Methods and Techniques for Chemical Transformations). We are also grateful to Dr Norman De ath (Radleys Discovery Technologies) for the loan of the RDT 24 place PTFE carousel reaction station. 

In the 18 years since its discovery, Wilkinson s catalyst has been used to hydrogenate all kinds of unsaturated compounds and great efforts have been made to develop other phosphorus ligand-containing catalysts of both rhodium and other metals. This in turn has led to catalytically active complexes which do not contain phosphorus. In Table 1 the hydrogenation of various unsaturated compounds catalysed by [RhCl(PPh3)3] is summarized. In some cases the addition of deuterium and tritium to the substrate was investigated.84,95,101,102... 

Retinyl esters 102a-c (1 mCirnl ) stored under argon at —60°C in toluene containing 40 /ig of 2-t-butyl-4-methoxyphenol and 4 pL of pyridine are quite stable. After 1 year about 60% decomposition was noted, due to radiolysis in the case of 102c. Retinoic acid 103 under similar conditions is also radiochemically stable, but after 4 months the material has to be repurified. Specific activities of tritium-labelled retinoids in the 10-40 Cimmol range have been found necessary in view of the discovery and use of cellular retinoid binding proteins. ... 

Samuel K, Yin W, Stearns RA, Tang YS, Chaudhary AG, Jewell JP, et al. Addressing the metabolic activation potential of new leads in drug discovery a case study using ion trap mass spectrometry and tritium labeling techniques. J Mass Spectrom 2003 38 211-21. 

Radioactively labelled proteins may be visualized without staining by autoradiographic methods which were first introduced by Becquerel and Curie in their discovery of the phenomenon of radioactivity (13.), or f 1 uorographic techniques for some of the weak beta emitters, such as tritium(M ). If the proteins are radioactively labled to a high specific activity, they can be detected with sensitivities equal and often better than those obtained by the most stains. However, the use of radioactively labled proteins is limited as it is difficult to achieve high specific activities in animal studies and unethical in reseach involving humans. 

It is obvious that in order to use Eq. (84) one must know the size of as well as the commitments ( /leq can be readily measured). It was the discovery by Northrop in 1975 that the deuterium and tritium isotope effects on V K could be compared to estimate that opened up the field of isotope effects on enzyme-catalyzed reactions (95) ... 

The incorporation of (36), (35), and (37) with increasing efficiency allowed further definition of the pathway to slaframine.The results indicate that a tritium label at C-1 of (36) is retained on formation of (39), and so (36) must follow (35) on the pathway. Further support for this relationship comes from the discovery that a cell-free extract of R. leguminicola would catalyse the NADPH-dependent reduction of (35) to (36). This extract also catalysed the acetyl-CoA-dependent formation of slaframine (39) from (38). The pathway to slaframine so far deduced is illustrated in Scheme 2. 

The discovery of deuterium in 1932 by Urey and tritium in 1939 by Alvarez and Corning opened up new techniques for catalytic studies. As previously stated Taylor organized the production of heavy water and used the deuterium so obtained to... 

---