This thesis concerns the study of reaction mechanisms by means of kinetic isotope effects (KIEs). Studies of the nucleophilic bimolecular substitution (SN2) reaction had the dual purpose of improving our fundamental understanding of molecular reactivity and assessing the ability of kinetic isotope effects to serve as mechanistic tools. The transition state of the SN2 reaction between a cyanide ion and ethyl chloride in tetrahydrofuran was found to be reactant like and only slightly tighter than has been found previously for the same reaction in dimethyl sulphoxide. One conclusion was that the transition-state structure in this reaction was predicted fairly well by the theoretical calculations, even without solvent modelling. The SN2 reactions between cyanide ions and para-substituted benzyl chlorides were found to have reactant-like transition states, of which the Cα-Cl bond was most influenced by the para-substitution. Theoretical calculations indicated that the chlorine KIEs could be used as probes of the substituent effect on the Cα-Cl bond if bond fission was not too advanced in the transition state. Furthermore, the nucleophile carbon 11C/14C KIEs were determined for the reactions between cyanide ions and various ethyl substrates in dimethyl sulphoxide. Precision conductometry was employed to estimate the aggregation status of tetrabutylammonium cyanide in tetrahydrofuran and in dimethyl sulphoxide, which is of interest as tetrabutylammonium cyanide is frequently used as the nucleophilic reagent in mechanistic investigations and synthetic reactions. The tendency for ion-pair formation was found to be very slight, significant, and very strong in dimethyl sulphoxide, water, and tetrahydrofuran, respectively. The nitrogen kinetic isotope effect on monoamine oxidase B catalysed deamination of benzylamine was determined in an attempt to obtain conclusive evidence regarding the mechanism of the oxidation. Monoamine oxidase is an important drug target in connection with the treatment of, for example, depression and Parkinson’s disease, and knowledge on how the enzyme effects catalysis would facilitate the design of highly selective and efficient inhibitors.

<p> The existence of significant and consistent fractionation of sulfur isotopes in natural coexisting sulfide mineral pairs is demonstrated. Such fractionations are shown to depend exclusively on the mineralogy of the assemblage and temperature of equilibration, consistent with a process of fractionation during equilibrium exchange of sulfur isotopes between the sulfide phases . The fractionation of sulfur isotopes between galena, sphalerite and pyrite has been determined experimentally over the temperature range 300-725°C . The fractionation for each mineral pair is shown to vary as T^(-2) so that three isotope geothermometer s have been calibrated. Experi mental results are applied to natural sulfide assemblages to determine the temperature of equilibration and extent to which isotopic equilibriurn has b een attained. </p> / Thesis / Doctor of Philosophy (PhD)