Tritium nuclear magnetic resonance spectroscopy chemical and pharmaceutical applications.

The development of 3H nmr spectroscopy has greatly increased the potential usefulness of tritium labelled compounds in chemical and biochemical research. The present study was undertaken in order to explore some of the applications of this technique in organic and pharmaceutical chemistry. The thesis is divided into six sections as follows: The General Introduction contains a literature survey highlighting the properties of tritium, the applications of 3H nmr spectroscopy already reported and some of the many procedures for tritiating organic compounds. In the first chapter the problem of referencing 3H nmr spectra and the determination of the Larmor frequency ratio is discussed; the latter was found to be dependent on bond hybridisation. The preparation of tritiated tetramethylsilane is also reported. Chapter two is concerned with the measurement of geminal coupling constants by a combination of tritium labelling of various organic compounds and 3H nmr analysis. This approach has certain advantages over the corresponding deuteriation procedure. Chapter three describes the application of a one-step catalytic procedure (using pre-reduced PtO2 and HTO) to the labelling of a number of drugs widely used in pharmacology. 3H Nmr analysis shows that the 3H is invariably incorporated into stable position. Labelling (both by 2H and 3H) of alpha,beta-unsaturated acids is considered in chapter four and this leads to a mechanistic study of the labelling of conjugated dienoic acids at both alpha- and beta-Positions. In the final chapter 3H nmr spectroscopy is applied to a study of the stereochemical aspects of the tritium labelling of 5-phenylpenta-2,4-dienoic acid