The project investigated the regioselectivity of 1,2,4-triazole with 1,1-diphenylepoxide. Typically N1 substitution was favoured over N4 substitution resulting in isomer ratios of 85-90/15-10. The kinetic factors affecting the regioselectivity were investigated and showed the importance of the 1,2,4-triazole anion. When 1,2,4-triazole reacted in the form of its ambident anion greater preference for the 1-isomer was observed. The use of low reactant concentrations and dipolar aprotic solvents were shown to increase the formation of the ambident anion. Under these favourable conditions the isomer ratio obtained was 95/5. Synthesis of new epoxides and subsequent reaction with 1,2,4-triazole had no effect on the regioselectivity. Thermodynamic control of the regioselectivity was then observed with the 1-alkyl-1,2,4-triazole being the thermally more stable isomer. The mechanism was shown to occur through the nucleophilic displacement of the triazole anion and formation of the epoxide. The 1-isomer was also seen to be the thermally more stable isomer regardless of the alkyl group and that it is formed in a ratio with the 4-isomer approaching the ratio found in the prototropic tautomer equilibrium of 1,2,4-triazole. Under thermodynamic control the equilibrium mixture was shown to be 99.3/0.7 by both experimental and theoretical (free energy diagrams) methods. From the literature other azoles are seen to exhibit thermodynamically controlled regioselectivity and are therefore also open to the predictive approach to their equilibrium isomer ratios from their respective prototropic tautomer equilibriums.

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Chapter 1 begins with a brief overview of molecular recognition and then presents a review of recently developed methods for lead generation and the synthesis of self-defining host molecules. Chapter 2 describes a strategy for the synthesis of functionally active molecules which combines advantageous features of some of the methods described in Chapter 1. Relevant literature and precedents are then introduced followed by a discussion of theoretical considerations. In Chapter 3, after an introduction to the use of cholate building blocks in supramolecular chemistry, the synthesis of the new steroidal molecules studied is described, together with a discussion of their structural properties. Chapter 4 outlines the development of an effective method for the reversible macrocyclisation of steroidal building blocks by transesterification. The application of this method to the thermodynamically-controlled, and metal ion-templated, cyclisation of the steroid derivatives is then discussed in Chapter 5. An investigation into the metal ion building properties of the steroid derivatives using electrospray mass spectrometry is described in Chapter 6. The chapter begins with initial experiments to explore the circumstances in which the technique can generate meaningful information and then summarises the metal ion binding characteristics of the steroids investigated. Chapter 7 explores transorthoesterification as a milder reversible reaction for the synthesis of macrocycles and then describes initial studies towards a host capable of binding a porphyrin guest. In Chapter 8, the results of the cyclisation experiments and the binding study are compared with each other and put into the wider context of the long term goals of the project. That is followed by some ideas for future directions of this work.

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