This project is in the field of chemo-catalysis. Catalysis is used somewhere in the manufacture of most everyday items (plastics, drugs, food supplements, flavours/fragrances, finishes and coatings). Amongst the most important reactions, generally used in the manufacture of diverse products such as varnishes, plastics, banana flavouring and anti-inflammatories!, are those that use carbon monoxide as a building block. Carbon monoxide is one of the cheapest chemicals and can come from coal, oil, gas and renewables. Due to the low price of carbon monoxide and the fact that it can, in the presence of a catalyst, react in a very clean fashion with other molecules, these catalytic carbonylation reactions generate very little waste and are economical even at very large scale (Millions of tonnes). These features also potentially make this type of reaction a clean and economical way to make much higher value, more sophisticated molecules such as drugs. However, to make these molecules, exquisite control of several types of selectivity is needed. For example, many drugs exist as two mirror image forms (optical isomers) and one isomer must be made prefentially. The other optical isomer is often inactive, or in fact can cause an alternative biological effect (The side effects of Thalidomide are a tragic example of one optical isomer causing unwanted biological effects). This has led to a massive research effort by chemists to develop chemical reactions that are capable of selectively producing a single optical isomer ('Asymmetric Synthesis'). Significant developments have been made in this area, with several Nobel prizes in chemistry being awarded to some of the pioneers in asymmetric synthesis. The investigators group has recently obtained exciting preliminary results developing catalysts that can control several aspects of selectivity in model studies on a few types of carbonylation, including excellent selectivity to one optical isomer. This new project addresses building on these results to develop routes to different target chemicals. Development of new types of carbonylation or the ability to work on hitherto unreactive substrates is needed for the higher value fine chemicals/pharma intermediates sector. A number of potentially exciting new reactions such as combining several reaction into one stage of a synthesis, and one reactor, one set of solvents, purification etc. are proposed. This project will also gain mechanistic insights on the new catalyst and use this information to generate refined catalyst design and rational design of catalysts to accomplish new tasks. Overall the project has the potential to impact on fundamental knowledge, generate proof of concept for new industrial targets, and provide better, more benign routes to a range of important chemicals.

This project will develop a new manufacturing process for making high value sequence-controlled polymers in a precise way. Sequence-controlled polymers include (bio)polymers such as DNA, RNA (together, "oligos") and peptides. They also include synthetic polymers for which precise control of polymer length or monomer order is necessary. These polymers are in demand by the pharmaceutical industry, where they are used as biologically active materials ("drugs"), and as parts of molecular assemblies that are used to deliver and protect drugs; and have emerging non-biological uses. Nature makes sequence-controlled polymers such as oligos or peptides by sequentially adding different monomers in a prescribed sequence. The exact order of that these monomers are added is absolutely crucial to the function of the final polymer. These same polymers are made by industrial chemistry in a way that apes Nature, through a sequence of monomer additions (we call this iterative synthesis), and a great deal of care is taken to remove the residues of unreacted monomer before the next cycle, to avoid errors in the sequence. A very effective way of doing this is to attach the growing polymer to a solid support phase, which is washed with clean solvents to remove the residues, before the next monomer is added. When polymer growth is complete, it is cleaved from the solid support. However this process is expensive, because more monomer must be used to ensure the reaction reaches completion on the solid support, and because the supports themselves are expensive. For synthetic polymers where we want to control the molecular weight exactly, for example poly(ethylene glycols) (PEGs), which are widely used to stabilise drugs and make them last longer in the body, we could add the same monomer over and over until we reach a desired chain length, and then cleave the final polymer from the support. This is not done at present, because the cost of solid supported iterative synthesis is too high and/or the chemistry is not available. There are other problems with solid supported synthesis. The solid supports are variable, and hard to make in a precisely repeatable way; in fact small differences in the supports can lead to quite big changes in the reactions used to link the monomers onto the growing polymer. Also, it is very hard to carry out analyses on the reaction mixture to tell whether the reactions are proceeding correctly, because the molecules of interest are inside the pores of a support material. Recent research at Imperial College has developed Organic Solvent Nanofiltration (OSN), using membranes that are stable in solvents, and able to separate small molecules from large molecules. Our key innovation is to use these membranes at each stage of sequence-controlled polymer synthesis to separate the growing polymer from the unreacted monomers. This process will be carried out in the liquid phase and analysis would be far more straightforward; and the reactions to grow the polymer will be faster and more efficient, and use less monomer. Further, if two or more of the growing polymers are connected to a hub molecule to create a homostar complex, this will make the solute to be retained by the membrane larger and promotes a more efficient separation. We propose this Iterative Synthesis with OSN, or ItSyN for short, as a new approach to precisely manufacture sequence-controlled polymers. The multidisciplinary team of chemical engineers and chemists who will work on the ItSyN project will develop the process chemistry to make the purification better; construct Lab Plant synthesisers so that the process can be automated, select solvents and explore solvent recovery, and use quality by design to make the process more efficient. If we are successful, the project will result in a new technology for sequence-controlled polymer manufacture, and will lead to more precise polymers being available for applications in healthcare and beyond.

The global need to move current human technologies into a sustainable future will have a great impact for the world of chemistry and related industries. In close concert with other disciplines, chemistry will be increasingly solicited to identify solutions that are practical, affordable and ultimately sustainable. To meet these objectives, not only research, but also chemical education will need profound reforms that have to be contextualized in the multidisciplinary and intersectoral picture of a sustainable development. It is propelled by these societal needs that, by educating and practising 14 ESRs, PHOTOTRAIN will ensure photo-triggered chemical process to play its central role in sustainability. By capitalising on the basic principles of supramolecular chemistry to program dynamic self-organized photoactive interfaces, it is intended to raise the creativity, knowledge, skills and capacity of the ESRs to conceive new ideas for reforming current industrial transformations into a new generation of “light-triggered” processes. The challenge of developing and transferring light-fuelled processes from a proof-of-principle to an exploitable process is to embark upon a dynamic configuration in which photoactive species are kept separated, act independently and are finally recycled. In particular, through the adoption of a microfluidic system in which programmed different phases allow the formation of photoactive interfaces, it is planned to implement photo-catalytic technologies at the industrial level for triggering stereoselective organocatalytic transformations (i.e., pharmaceutical applications) and/or solar fuels production. By the organisation of targeted individual projects and interdisciplinary secondements, ESRs will be guided toward attractive early-stage career opportunities as researchers, process chemists, chemical engineers and research managers in collective forms at various academic and research institutes, small and large enterprises, and NGOs.

Synthetic biology has the potential to revolutionise the way we make a host of consumer products from materials and energy to food and medicine. In order for this impact to be realised, we must find the best way to translate laboratory discoveries into operating industrial production processes. The challenge here is to transition from existing factories into the factories of the future. Today many consumer products are made from fossil resources using synthetic chemistry techniques. In the future we will need to reduce our dependence on petroleum products and move to renewable resources. At the same time, the advent of synthetic biology techniques for rapidly tailoring biological systems for manufacturing purposes will allow us to transition away from synthetic chemistry and into more environmentally friendly production mechanisms using cells. We will tackle the question of how to undergo this transition smoothly by working with our industrial partners on real-world applications in two consumer areas (therapeutics and chemicals manufacturing). Developing these future biofactories will require the invention of some new generalised technologies to underpin the new manufacturing processes. We will need new biologically based sensors in order to be able to monitor the production processes as they occur to ensure the product quality (and to allow us to intervene if necessary). We will also need new, more robust production cells that can tolerate the high levels of compounds they make and new microreactors and/or compartmentalisation strategies for using enzymes when whole cells are not required. Because the transition will not happen overnight, we will need to develop intermediate production methods that combine biological and chemical catalysts. This will require solvents that are less toxic to proteins and cells and proteins that are engineered to be more robust in the presence of chemicals. In order to develop processes that are economical and efficient (minimal energy and water usage), we will create computer models to compare alternatives. The most promising processes will be implemented in the factories of our industrial partners. We have chosen two challenge areas in which to test our new technologies. The first is healthcare, specifically the manufacture of medicinal compounds and therapeutic proteins. These are already largely made using biological systems, but the existing processes are expensive and complicated. Also, in the future, it would be more efficient to make these medicines as and when they are needed (point-of-care manufacture). Our goals are to make simpler, more cost effective, point-of-care manufacturing systems using a combination of the above mentioned platform technologies: enzyme microreactors, specialised cells, and biosensors. Our second target is to produce bulk chemicals without the need for petroleum inputs. This will require us to adjust our manufacturing techniques for renewable inputs (such as biomass) and to develop new processes that use biology and/or environmentally friendly chemistry to do the conversions. Synthetic biology has never been attempted on such a large scale. Our challenge will be to adapt our parts, devices, and systems to operate at this level. The overall outcome will be novel, cost effective, energy efficient, and sustainable routes to therapeutics and chemicals.

This project aims to deliver the underpinning tools and design principles to support the use of water as a reaction media in High Value Chemical Manufacture. Water has long been promoted as an environmentally friendly and safe 'green' reaction media for synthetic processes which can lead to much more sustainable and cost effective manufacturing process. Nevertheless, the green credential of water has been limited due to issues related to organic contamination of the water waste stream, cost of subsequent treatment and the often required organic solvents at purification stage. Water-accelerated reactions, i.e. reactions which proceed faster in water than in organic solvents and wherein organic reactants and products form hydrophobic droplets, are potential game-changers High Value Chemical Manufacture. They benefit from accelerated rates, improved productivity and much improved green metrics through reduction in the use of organic solvents. Their current limitations are: (i) a limited pool of known reactions; (ii) lack of suitable equipment and process understanding; and (iii) insufficient understanding of acceleration effects which can guide discovery and process design. This project will address these knowledge gaps and deliver the following critical outputs, identified through discussion with our industrial partners in chemical industry sector: (i) a wider range of synthetically useful water-accelerated reactions, (ii) multi-scale batch and flow reactors to support the scale-up pathway for water-accelerated processes, (iii) standardised protocols for characterising such processes and basic process understanding for scaling up, and (iv) streamlined workup/product purification and recycling of water to truly deliver green processes. These outputs will have transformative impacts in the chemical manufacture industry, delivering lower cost and better quality controlled processes through shorter routes, reduced organic waste and facile interfacing between chemo- and biocatalytic processes.