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Synthetic Helical Oligomers as a Novel Class of Bioinspired Catalysts
Secondary Supervisor(s): Dr Sarah Pike, Dr Fredrik Schaufelberger
University of Registration: University of Warwick
BBSRC Strategic Research Priority: Understanding the Rules of Life (Structural Biology, Systems Biology)
Project Outline
Synthetic catalysts are widely used in an array of everyday processes including energy production, the synthesis of pharmaceuticals and agrochemicals and the production of plastics. However, many existing synthetic catalysts display poor activity or low selectivity in environmentally friendly mediums (e.g. water) and hence are often applied in (toxic) organic solvents, which have adverse environmental impact. Furthermore, many synthetic catalysts are composed of rare or precious metals, which are low in natural abundance, are highly unsustainable and have a negative environmental footprint. Consequently, in recent years there has been a drive towards the development of sustainable synthetic catalysts that avoid the use of precious/rare metals and which operate in more environmentally friendly solvents (e.g. water).
Synthetic helical oligomers (“foldamers”) are bioinspired scaffolds that adopt secondary structures, e.g., helices, that are reminiscent of the folding behaviour of natural systems (e.g. DNA and protein helices) (Fig. 1).1,2 These bioinspired systems have found widespread applications in an array of fields, including catalysis. However, despite recent advances, foldamers that operate as catalysts lack the ability to function in environmentally friendly, aqueous and biocompatible conditions.
Figure 1. Foldamer in the solid state. a) viewed side on, b) viewed from the N terminus.
Chalcogen bonding is an unconventional non-covalent interaction, which is thought to underpin the activity of certain biological macromolecules (such as glutathione peroxidase), however it’s use in catalysis is currently under-represented. Significantly, the hydrophobic nature of chalcogen bonding allows the formation of strong non-covalent interactions in water,3 and provides great potential to design catalysts that function in biocompatible conditions.
Herein, we will develop a new class of bioinspired foldamers that exploit chalcogen bonding interactions to operate as effective catalysts in biocompatible conditions (e.g. water). We will explore structure-activity relationships (SARs) of libraries of these new catalysts to gain an understanding of the fundamental factors that govern chalcogen bonding behaviour to enable optimisation of catalytic activity.
Objectives
(1) To develop synthetic libraries of foldamers with systematic variation in a range of fundamental features, including: i) nature of the chalcogen atom in the catalytic site (e.g. S vs Se), ii) foldamer topology; iii) number of catalytic binding sites, and iv) distance between catalytic sites.
(2) To perform conformational analysis of the new foldamers in a range of organic solvents and water. These studies will establish the influence of the fundamental variations introduced to the foldamer structure in Objective 1 on its’ conformational behaviour (i.e. size/shape). This will provide a broad range and variety of catalysts for subsequent SAR studies in Objective 3.
(3) To assess the catalytic activity of the new foldamers and ascertain their ability to perform biologically relevant reactions (e.g. carbon-carbon bond forming reactions, Michael additions, etc.) in a range of solvents and establishing their performance as effective catalysts in water. Optimisation of catalytic activity will be achieved through investigation of the SARs of the designed foldamer libraries.
This work will create a new class of bioinspired catalysts based on foldamers that can perform reactions in biologically relevant solvents for the first time.
Methods
A combination of synthetic organic chemistry and advanced analytical study is required to realise the project and generate a new class of bioinspired foldamer catalysts and assess their stability and performance in water. This work will be carried out under the supervision of Drs Pike (Birmingham) and Greenhalgh (Warwick).
References
1. a) D. J. Hill et al., Chem. Rev., 2001, 101, 3893; b) P. Sang et al., Chem. Soc. Rev., 2023, 52, 4843.
2. S. J. Pike et al., Org. Biomol. Chem., 2023, 21, 7717.
3. F.-U. Rahman et al., J. Am. Chem. Soc., 2020, 142, 5876.
