Dynamic Molecules with Switchable Hydrogen-Bond Directionality

  • David T J Morris

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

Nowick and co-workers have reported that ethylene-bridged triureas can be synthesised with complete conformational control by judicious use of steric hindrance and hydrogen bonding.1 The concept of complete but switchable conformational control of these structures has not been investigated and is of interest as it gains access to dynamic peptide mimics with switchable hydrogen-bond directionality.

Previous work in the Clayden group has shown that achiral oligourea-derived foldamers can communicate stereochemical information by binding a chiral ligand and inducing a helical excess.2 This served as the first example of reversible hydrogen-bond directionality in a synthetic foldamer. In our design, the global directionality of an ethylene-bridged oligourea foldamer can be controlled by applying an electronic bias at one terminus. When terminated with a hydrogenbond acceptor (HBA), the global directionality of the foldamer is defined and controlled owing to the hydrogen bond between the HBA and the ureido proton of the adjacent urea, and the hydrogen bonding between the ureas in the foldamer. The orientation of the final urea can be inferred from variable-temperature 1H NMR and NOE studies of the ureido protons and a benzylic methylene spectroscopic reporter. The opposite directionality can be accessed by using a terminal hydrogen-bond donor (HBD) instead of an HBA. The directionality of these foldamers can be switched by employing a terminal 2-pyridyl group, which can be switched between an HBD and an HBA by protonation/deprotonation. Upon protonation, the first urea reorients in order to hydrogen bond to the resultant pyridinium. This reorientation is communicated as binary information throughout the rest of the foldamer, resulting in a global directionality switch. Preliminary experiments on effecting the switching process with the light-induced photodissociation/association of a photoacid have been performed. Investigations into directionality-switchable foldamers with binding sites complementary to those of DNA nucleobases have been conducted. Different spectroscopic or chemical outputs at the reporting terminus have also been explored.

Ethylene-bridged oligoureas represent a new class of foldamers that can undergo a global directionality switch in response to pH change or exposure to light, and could be amenable to DNA ligand binding. The concept of switching hydrogen-bond directionality in foldamers is a significant simplification of how biological systems store and communicate information and could provide access to interesting and useful chemical and biomimetic functions.
Date of Award23 Jan 2020
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorJonathan P Clayden (Supervisor)

Keywords

  • Foldamers
  • Hydrogen bonds
  • Intramolecular Communication

Cite this

Dynamic Molecules with Switchable Hydrogen-Bond Directionality
Morris, D. T. J. (Author). 23 Jan 2020

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)