Enantiomeric excess determination using circular dichroism spectroscopy and studies of reversible covalent reactions

The unifying topic of this thesis is that of supramolecular and reversible covalent chemistry. Both supramolecular and reversible covalent reactions operate under thermodynamic control, leading to a proofreading effect and equilibration to the most stable structures. Similarly, these systems are able to respond to applied stimuli, making them useful for the development of sensors, as well as the templated formation of receptors and drug-like molecules. Part 1 of this thesis focuses on the development and improvement of supramolecular and reversible covalent systems for the determination of enantiomeric excess using circular dichroism spectroscopy. We were able to improve the error of enantiomeric excess determination by exploiting the Majority Rules effect exhibited by certain helical polymers. Determination of the enantiomeric excess of a sample using optical methods generally requires the generation of a calibration curve, requiring the availability of enantio-enriched samples with known enantiomeric excess. Our group showed that Charton parameters can be used to predict circular dichroism values of our assemblies upon incorporation of new analytes, circumventing the need for a calibration curve. However, the number of Charton parameters tabulated in the literature is limited, and measurement of these parameters is non-trivial. Therefore, we decided to explore the use of computationally derived Sterimol parameters for the prediction of calibration curves. Part 2 of this thesis focuses on the topic of dynamic covalent reactions for the use in dynamic combinatorial chemistry. We were able to find a set of four reversible covalent reactions that react reversibly under identical reaction conditions and do not exhibit any cross-reactivity, which was unprecedented. Based on these four reactions, we set out to develop photo-cleavable protecting groups for the functionalities used in those reactions. We also developed photo-cleavable reaction partners that would be able to react in a dynamic combinatorial fashion with other reactive groups, but would release their reacting partner unchanged upon photolysis. Finally, we set out to study the reaction kinetics and mechanism of aniline-based catalysis of hydrazone exchange using linear free energy relationships, allowing for fine-tuning of the exchange rate