Exploiting chirality in mechanically interlocked molecules for new applications in nanotechnology

In pioneering publications in Science(1) and J. Am. Chem. Soc.(2) molecular knots have been shown by the Leigh group to have promising catalytic properties due to their well-defined cavities and well-expressed chirality.(1,2) Pentafoil knots, in particular, show very strong affinities for halide anions as a combined result of the multiple hydrogen bond and coulombic interactions that can be utilised for anion binding catalysis.(3) Furthermore, the catalytic activity can be allosterically switched on and off by the addition or removal of metal ions that template the cavity formation in a manner reminiscent of allosteric control in enzymes.(1)
This project will aim to prepare a range of molecular knots that contain photoredox-active Ir(III) centres in place of the previously used first row transition metal centres.(1,4 )The iridium centres will play a dual role: Firstly, the relative inertness of Ir(III) allows the isolation of the starting materials as single enantiomers.(5) Due to the required symmetry of the circular helicates, the use of an enantiopure Ir(III) complex should result in the stereoselective synthesis of the knot precursor. Secondly, cyclometallated Ir(III) complexes bearing a bipyridine ancillary ligand are well documented as effective visible light photoredox catalysts.(6)
By incorporating photoredox active components into a helicate of single-handedness we aim to achieve stereoselective dual photoredox/anion binding catalysis. As an example, the two step nucleophilic attack of tetrahydroisoquinolines can be promoted by a combined mixture of a photoredox catalyst and an enantioselective hydrogen bond donor catalyst.(7) This process could be achieved in a one pot procedure using Ir(III) knots. We propose controlling the reaction via allosteric interactions using different metal ions as signalling systems. The removal of first row transition metal ions will prevent the system from acting as an anion binding catalyst whilst the photoredox properties will be unaffected. The addition of Fe(II) to template the cavity will allow anion binding but quench the photoredox process. Finally, the addition of Zn(II) should allow both photoredox and anion binding catalysis to work in tandem.
This project aims to merge a range of important and emerging areas including molecular knots, photoredox catalysis and switchable catalysis to provide systems capable of catalysing reaction pathways with strict control over both the stereochemistry and regiochemistry in a manner reminiscent of biological systems. Molecular knots are an emerging field with promising potential for switchable catalysis. Chemical topology provides a to date untapped strategy for retaining molecular connectivity whilst altering function. Any progress in using chemical topology to alter reaction pathways would be at the forefront of the field. Whilst the use of photoredox catalysis as a green and mild synthetic method is rapidly on the rise, stereoselective photoredox processes are still in their infancy. Any enantioselectivity achieved using photoredox catalysis would be a significant addition to the current state-of-the-art. Nature is able to finely tune the reaction rate of many complex pathways via allosteric interactions with a wide range of different signalling molecules. The ability to alter synthetic reaction pathways opens the possibility of creating smart systems capable of responding to different stimuli. This project aims to combine a range of emerging technologies to create new and exciting functional catalysts for future applications.
1. V. Marcos et. al., Science 2016, 352, 1555-1559.
2. G. Gil-Ramirez et. al., J. Am. Chem. Soc. 2016, 138, 13159-13162.
3. J.-F. Ayme et. al., J. Am. Chem. Soc. 2015, 137, 9812-9815.
4. D. A. Leigh, et. al., Nat. Chem. 2014, 6, 978-982.
5. O. Chepelin et. al., J. Am. Chem. Soc. 2012, 134, 19334-19337.
6. C. K. Prier et. al., Chem. Rev. 2013, 113, 5322-5363.
7. G. Bergonzini et. al., Chem. Sci. 2014, 5,1-60

iCAT will work with industry partners to create an holistic approach to the training of students in biocatalysis, chemocatalysis, and their process integration. Traditional graduate training typically focuses on one aspect of catalysis and this approach can severely restrict innovation and impact. Advances in technology and fundamental reaction discovery are rendering this silo-approach obsolete, and a new training modality is needed to produce the next generation of chemists and engineers who can operate across a far broader chemical continuum. iCAT will meet this challenge with a state-of-the-art CDT, equipping the next generation of scientists and engineers with the skills needed to develop future catalytic processes and create the functional molecules of tomorrow.

The UK has one of the world's top-performing chemical industries, achieving outstanding levels of growth, exports, productivity and international investment. The UK's chemical industry is a significant provider of jobs and creator of wealth, with a turnover in excess of £50 billion and a contribution of over £15 Billion of value to the UK economy [2015 figures]. iCAT will deliver highly skilled people to lead this industry across its various sectors, achieving impact through the following actions:

1. Equip the next generation of science and engineering leaders with the interdisciplinary skills and knowledge needed to work across the bio and chemo catalytic remit and build the functional molecules we need to structure society.

2. Provide a highly skilled workforce and research base, skilled in the latest methodologies, strategies and techniques of catalysis and engineering that is crucial for the UK's Chemical Industry.

3. Build the critical mass necessary to support effective cohort-based training in a world-class research environment.

4. Develop and disseminate new catalytic technologies and processes that will be taken up by industrial and academic teams around the world.

5. Encourage Industry to promote research challenges within the CDT that are of core relevance to their business.

6. Provide cohesion in the integration of biocatalysis, engineering and chemocatalysis to create a more unified voice for strategic dialogue with industry, funders and policy makers, and more generally outreach and public engagement.

7. Draw-in and bring together Industrial partners to facilitate future Industrial collaborations.

8. Benefit Industrial scientists through interactions with the CDT (e.g. training and supervisory experience, exposure to cutting-edge synthesis and catalysis etc).

9. Link with other activities in the landscape: bringing unique expertise in catalysis to, for example, externally-funded University-led initiatives, EPRSC Grand Challenge Networks, and the National Catalysis Hub.