Pump up the volume: Foldamers as molecular amplifiers

different compartments. This cellular compartmentalisation by membranes permits the separation of incompatible catalytic conditions. A similar incompatibility often occurs when attempting to link aqueous biocatalysis with chemocatalysis that has been optimised in organic solvents.
Molecular information relays developed in the Webb group could provide an exciting solution to this problem. These relays transmit information along multi-nanometre distances, which allows them to operate simultaneously in aqueous and hydrophobic environments.[1],[2] At their core is an amphiphilic alpha-aminoisobutyric acid (Aib) foldamer that adopts well-defined helical conformations. Incoming information causes a change in structure at the N-terminus (e.g. an M to P helicity switch) that is relayed to the far end of the foldamer. Webb has shown these foldamers can relay chiral information from an aqueous chemical messenger deep into the hydrophobic region of a membrane to produce a spectroscopic output. We now wish to produce chemical messengers using biocatalysis and to replace the spectroscopic output with chemocatalysis. The outcome will be an information relay that amplifies the chiral output from an enzyme by inducing enantioselectivity in a chemocatalyst; producing a synthetic signalling cascade.
The Turner lab will provide the first part of the signalling cascade, by screening for potential ligands (carboxylates, phosphates) that can be produced by biocatalytic processes, e.g. by the action of kinases, dehydrogenases etc. Webb and Turner previously found that Candida antarctica lipase B hydrolyses rac-BocProOMe in water to give Boc-D-Pro with high enantioselectivity.[3] This is a known active signalling molecule, but this enzyme has not yet been screened against membrane-embedded foldamers. Similar Aib foldamers can report on the e.e. of mixtures produced through organocatalysis,[4] so alternatives include the kinetic resolution of racemic carboxylates (transformation of one enantiomer into a non-binding product such as an aldehyde, amide or lactone) or the enzymatic transformation of achiral substrates into chiral carboxylates.
The next part of the signalling cascade will use Aib foldamers that bear N-heterocyclic carbenes (NHCs) at their C-terminus, which permits access to organometallic catalytic "write heads". The first generation of catalytic "write heads", foldamer-Rh(I) complexes, have been shown in the Webb lab to reduce ketones to chiral alcohols. More catalytic reactions need to be developed (e.g. alkyne hydrosilylation) and other catalytic write-heads, such as Ru(II)-NHC complexes for ROMP, synthesised.
The student will receive broad multidisciplinary training. The project will start with the chemical synthesis of Aib foldamer-organometallic complexes and analysis of their catalytic performance in organic solvents, including tolerance to low levels of water. In parallel, ligand screening will be performed and enzymatic systems developed that are compatible with phospholipid vesicles and able to generate enantioenriched carboxylate. Finally a recognition motif will be installed, and the performance of the molecular construct assessed when in vesicles.
This project combines chemocatalysis with biocatalysis to create a synergistic chemo/biocatalysis cascade. Furthermore the student will work closely with PDRAs using Aib foldamers in Webb's current EPSRC-funded research in molecular robotics, bolstering efforts in this area.

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.