Artificial Transmembrane Signalling and Cooperativity in H-Bonded Networks
Supramolecular chemistry is the study of non-covalent interactions and applications in the assembly of complex systems where multiple components interact with each other. This thesis addresses these two areas, with a first project on artificial transmembrane signalling, and a second on cooperativity in hydrogen bonded networks.
Cells rely on complex signal cascades where proteins are responsible for the transmission and amplification of chemical signals across membranes. While numerous examples of biomimetic synthetic transport systems are reported in the literature, this first project focused on the development of membrane-anchored molecules capable of communication across the lipid bilayer of vesicles by exploiting an artificial transduction mechanism. The signalling relies on molecular motion across the bilayer which is controlled by switching the polarity of two different head-groups. A new external redox input signal based on ascorbic acid was successfully employed to trigger membrane translocation and signal amplification via activation of an internal catalytic process.
Hydrogen bonds play a major role in determining structure and function in biology, chemistry and materials science. A few examples in the literature report cooperativity in hydrogen bonding networks involving hydroxyl groups. However, the magnitude of this effect is difficult to quantify experimentally. The aim of the second project was to develop a systematic structure-activity approach to the quantification of cooperativity. A series of phenol oligomers containing intramolecular hydrogen bonds was designed to make quantitative measurements of the effects of the intramolecular interactions on the strengths of intermolecular hydrogen bonding interactions between the terminal phenol hydrogen bond donor and hydrogen bond acceptors. Intramolecular hydrogen bonds strengthened the intermolecular hydrogen bond by up to 14 kJ mol⁻¹. The experimental results were corroborated by computational studies and a simple model for cooperativity in hydrogen bonded networks was proposed. The formation of each intramolecular hydrogen bond in the chain increases the polarity of the next hydrogen bond donor by 33%. A series of bisphenols variously substituted in the para position allowed to quantify the substituent effect. Addition of a para-nitro substituent to the phenol that acts as the intramolecular hydrogen bond donor strengthened the intermolecular hydrogen bond with the other phenol by 16 kJ mol⁻¹, and the effects of different substituents correlate with the corresponding Hammett parameters. Finally, a study of the hydrogen bonding donor properties of a series of benzyl alcohols intramolecularly hydrogen bonded to a phenol showed that changing both the size of the ring involved in the intramolecular hydrogen bond and the nature of the hydroxyl donor on the end of the chain had no significant impact on the magnitude of the cooperative effect.