Conformational control in hydrogen-bonded oligourea helices

  • Romina Wechsel

Student thesis: Phd


Helical foldamers offer variety and flexibility in the design of molecular systems, with different types of backbone geometry and side chains available to influence both structure and function. Such foldamers based on an aliphatic N,N'-linked oligourea backbone have been studied in recent years and have been shown to form very stable hydrogen-bonded 2.5(12/14) helices. This project investigated the creation of hydrogen-bonded oligourea helices to explore concepts of conformational control. Both an achiral helical system with a single chiral influence and meso oligourea helices were synthesised and analysed.The formation of a helical conformation was achieved in an achiral oligourea helix consisting of gem-dimethyl residues using a single terminal chiral controller unit based on cis-1,2-diaminocyclohexane (Dac). A preferred screw-sense was established in some oligomers, and the structural importance of the gem-dimethyl side chains and the terminal substituents was demonstrated. Urea-linked meso homo-oligomers of Dac were found to adopt a stable helical conformation, and values for their barriers of screw-sense inversion could be calculated.Conformational control of meso oligourea helices was explored through two main approaches: (i) intrinsic screw-sense preference through symmetry-breaking and (ii) the use of ligands to either induce or invert screw-sense preference.The synthetic precursors of meso oligoureas are chiral as they possess two different terminal substituents, which breaks the meso symmetry. Amplifying the difference in hydrogen-bonding capabilities of terminal substituents allowed control over the screw-sense preference of such oligomers. Binding of a chiral carboxylate ligand (Boc-D-Pro) to a meso oligourea led to a bias in screw-sense equilibrium; the binding affinity and a 1:1 ligand-foldamer complex stoichiometry were established. Finally, selective binding of achiral anions (AcO-, H2PO4-) to one terminus was used to achieve inversion of screw-sense preference of chiral oligourea helices. This research represents the first investigation of meso oligomers and uses conformational control through symmetry and symmetry-breaking as a novel concept.
Date of Award31 Dec 2016
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorSimon Webb (Supervisor)


  • oligourea
  • foldamer

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