Applications and Synthesis of [2]Rotaxanes for Artificial Molecular Machines

  • Adrian Haertsch

Student thesis: Phd


Molecular machines are ubiquitous in nature and drive almost all important biological processes. In the past couple of decades, chemists have become interested in mimicking the behaviour of biological machines with small molecule molecular machines. In this context, mechanically interlocked structures like [2]rotaxanes have played a significant role. Herein we explore the application and synthesis of novel [2]rotaxane architectures to solve different problems encountered in the field of molecular machines. Firstly, a molecular walker based on a [2]rotaxane architecture is explored. The mechanically interlocked structure renders each walking step highly directional, which was not the case for previously reported small molecule walkers. The herein reported system might serve as a platform to explore the application of molecular fuels to walkers. If successful, this could be the next step towards fully autonomous small molecule walkers. Secondly, [2]rotaxanes are explored for the sequence specific synthesis of peptides. In this context, the direct aminolysis of thioesters is explored as a new mode of operation. It was hypothesised that this type of reactivity could help to circumvent some of the limitations of previous designs. Thioester-based molecular machines were synthesised and operated, however initial operations with a 3-barrier machine remain unsuccessful. Further investigations will be necessary; however the synthesis of the machines is challenging and it remains to be seen whether large enough quantities can be synthesised to thoroughly investigate this system. Finally, a new C(sp3)–C(sp3) bond forming reaction reported by Baran and co-workers is explored for the synthesis of asymmetric traceless [2]rotaxanes where the axle does not contain any obvious retrosynthetic disconnection. The methodology successfully furnished the desired species; however a symmetric homo-coupling product was also obtained. Based on this unexpected observation, potential implications for the mechanism of the reaction are discussed.
Date of Award1 Aug 2020
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorDavid Leigh (Supervisor) & Michael Greaney (Supervisor)


  • molecular machines
  • molecular walkers
  • [2]rotaxanes
  • artificial peptide synthesisers
  • active metal template

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