Artificial Molecular Machines

UoM administered thesis: Phd

  • Authors:
  • Burkhard Groh

Abstract

During this degree two main projects have been investigated related to the design and operation of rotaxanebased synthetic molecular machines. The first system explored aims to mimic ribosomal peptide synthesis as a paragon of an ideal molecular assembler. It relies on the concept of constructing molecules by translating a given piece of information encoded as a sequence of reactive barriers installed on the machine’s track into a predetermined product (Figure 2.1). The basis of the translation chosen uses Wittig chemistry to construct stilbene sequences under basic operation conditions from an aldehyde macrocycle and several bifunctional aldehyde phosphonium units through a succession of carbon-carbon bond forming reactions. Figure 2.1. Helicene synthesis by a rotaxane-based molecular machine. The operation affords stilbene sequences that can be converted to helicenes via oxidative photocyclization. During this study we have been able to show that when applying a phenanthrene motive, stilbenes obtained from the operation of the machine can subsequently be transformed into helicenes with the aid of light and an oxidant. We showed that applying this concept the two-step operation of a one- and two-barrier machine successfully yields [5]- and [9]helicenes, respectively, which could be isolated and characterised. It was noticed that in contrast to the absence of selectivity for the E–Z ratio of standards, the corresponding stilbene products from the operation are formed preferentially in one of the possible configurations. As a second project, we have been working on a system that relies on the group’s design of a rotary and linear motor system (Figure 2.2). It is based on the successive uptake, pH-induced shuttling between two different stations (blue to orange) and final release of a macrocycle (red) from and back into bulk solution. And it controls the direction of the macrocycle’s translation with a pair of barriers that become labile under orthogonal conditions for hydrazone (yellow) and disulfide exchange (purple). It is combined with dissipative pulses of a chemical fuel to give an autonomous molecular pump. To complement the analysis and further corroborate the translation process we developed a design that includes a fluorophore unit. We anticipated that with the aid of a switchable intramolecular fluorescence quenching process an indication of the macrocycle’s position and its motion during the operation can be inferred. We postulated that in our example, the intermediate binding of a crown-ether macrocycle to a methyl triazolium unit could modulate the fluorescence of a proximal fluorophore. The design has the potential to allow measuring the kinetics of the dethreading and importantly, it has the capacity to directly visualise each pump cycle. Figure 2.2. Chemically fuelled unidirectional linear transport of 27C9 with pyrene-based rotaxane pump 2/2∙H+ indicating the position of the macrocycle with a fluorescence read out. At the current stage of investigations, a series of improved designs were developed, a working bistable pump synthesised, and its operation attempted. We were able to establish a procedure that allows isolation of intermediate hydrazone (pseudo)[2]rotaxanes. This allowed testing their switching properties with NMR and fluorescence spectroscopy and we were able to successfully show reversible threading and shuttling. Furthermore, we were able to single out an optimal size for the pump’s macrocycle and improve the conditions for its operation. Besides this, a system of two fluorophores (anthracene and pyrene) was identified that could be applied as a potential pair of orthogonal fluorescence indicators for the simultaneous monitoring of two machines. Future work will involve optimising the last dethreading step of the operation with the final pump design and examining the kinetics with fluorescence spectroscopy.

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Original languageEnglish
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Award date1 Aug 2021