Determining the strength of H-bonds in solution can be challenging due to competing solvent interactions, especially in biologically relevant polar solvents such as water. In this thesis, various molecular balance designs are used to quantify the strength of H-bonds in solution. Chapter 1 presents a literature review on optimising H-bond interactions, with a focus on experimental systems previously used to quantify the strength of H-bonds in different solvents. Chapter 2 investigates the effectiveness of implicit solvation models for predicting the thermodynamic behaviour of different solvents using a simple series of molecular balances. Computationally determined equilibrium energies are compared with experimental values. Generally, the implicit solvation models are found to have good correlations in non-polar solvents, but poorer results are observed when moving onto more polar solvents. Chapter 3 provides an experimental study of organic and aqueous solvent effects on intramolecular H-bonding between amide and anilines. Several series of compounds are investigated, where both H-bond geometry and conformational flexibility are varied. Thermodynamic information is derived from the balances and the experimental data examined further by plotting against computational results and fitting with a semi-empirical solvation model. Chapter 4 presents a study on solvent effects on H-bond cooperativity. A phenol, catechol and pyrogallol molecular balance series are synthesised and experimental energies are derived. Three different types of behaviour are observed depending on the acceptor ability of the solvent.
