Molecular torsion balances for quantifying non-covalent interactions
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Non-covalent interactions underpin the whole of chemistry and biology, but their study is extremely difficult in complicated biological systems. This thesis presents the application of synthetic molecular balances for gaining fundamental insights into the physicochemical phenomena that govern molecular recognition processes. Chapter 1 reviews the use of small synthetic molecules that exist in two conformational states via slow rotation of a bond, in the quantification of non-covalent interactions. Chapter 2 presents a new molecular torsion balance, based on a slowly rotating tertiary formyl amide for the study of non-covalent interactions. The incorporation of a fluorine atom in one of the rings allows the quantification of solvent effects in a wide range of solvents. Intramolecular electrostatic interactions and intermolecular solvation effects (but not solvophobic effects) are shown to be important in determining the position of the conformational equilibria. Correlations with calculated molecular properties show that solvent effects are fully dissected, revealing the idealistic behavior of the system in the gas phase. Chapter 3 discusses through-space substituent effects on the properties of aromatic rings. Electronic communication between both electron-rich and electron-deficient substituents with the electron density of an adjacent aromatic ring is predicted by molecular electrostatic potential calculations. The effect is confirmed to occur experimentally and is quantified using synthetic molecular balances. Chapter 4 describes the work done towards the investigation of solvent bridging interactions in molecular torsion balances. No experimental evidence of bridging interactions was observed. This might be attributed to the entropic penalty associated with this binding mode, or the non-ideal geometry of the potential bridging sites. Chapter 5 outlines a steric blocking effect observed in certain balances with bulky substituents in chloroform and dichloromethane. Chapter 6 presents synthetic procedures and compound characterisation including a thorough analysis of NMR data obtained in this study.