Asymmetric catalysis has revolutionized the way molecules are made and are essential to the continued production of myriad products from small bioactive molecules to materials and from small scale to manufacture. A number of these processes have become privileged, with their impact demonstrated from tonne-scale application to the Nobel Prize. Increased mechanistic understanding of catalytic reactions underpins improvements of existing processes while driving development of new methods. By interrogating reactivity and selectivity in a newly described reaction, this proposal aims to bring new understanding to the underpinning catalytic processes while providing methods for the preparation of novel and synthetically powerful architectures. Our preliminary studies using asymmetric protonation have recently been published and provide a solid foundation for the proposed work. A series of additional supporting proof-of-concept experiments in support of this proposal have also given strong confidence in being able to deliver upon the objectives and aims of this proposal. This proposal will comprehensively investigate this asymmetric protonation platform to allow predictability and the rational application of this chemistry as a method for the generation of scaffolds tailored towards application in Medicinal Chemistry, with specific applications within Chemical Development in collaboration with our industrial project partner.

Functional molecules (such as polymers, surfactants, ionic liquids and solvents) and structured phases (such as crystalline materials, micelles and liquid crystals) are of immense industrial importance in areas ranging from the traditional chemical and petrochemical sectors to the personal care, pharmaceutical, agrochemical and biotechnology sectors. Large strides in our ability to model matter from the molecular to macroscopic scales have been made in recent years, and it is timely to exploit these advances to make more rational design decisions in developing new materials. MOLECULAR SYSTEMS ENGINEERING focuses on the development of methods and tools for the design of better products and processes in applications where molecular interactions play a central role. By MOLECULAR we refer to the development of predictive models that are built upon a fundamental understanding of the behaviour of functional molecules, and which rely on physically meaningful parameters. The resulting models should incorporate the most up-to-date scientific knowledge and be accessible to non-experts. By SYSTEMS we refer to the development of techniques that are generic and can therefore be used to tackle problems in a range of applications. We place particular emphasis on the correct and efficient integration of models across different scales, so that molecular-level models can be used reliably at the larger scale of products and processes. By ENGINEERING we refer to our focus on applications where the key issue is to achieve desired behaviour, be it optimal end-use properties for a product or optimal performance for a manufacturing process. This research programme thus aims at addressing the general grand challenge of finding molecules, or mixtures of molecules, which possess desired properties for their end-use and for processing. A multidisciplinary team of systems engineers and thermodynamicists will develop modelling approaches to address generic problems in predicting the behaviour of matter, and will apply them within computer-aided design tools to solve problems in four important areas of application: the promotion of organic reactions in solvents, polymer design, the design of effective drug crystals, the design of structured materials such as polymer blends, microemulsions (e.g. shampoos) and liquid crystals.

The focus of research in Molecular Systems Engineering is the development of methods and tools for the design of better products and processes in applications where molecular interactions play a central role. To date we have developed a successful activity focussed mostly on large-scale gas-liquid processes. A strategic objective of this proposal is to make a leap to the more challenging high-value manufacturing arena, where formulated and structured products are prevalent. The combination of fundamental physical understanding, mathematical models, and numerical methods is the cornerstone of our approach. It allows us to reduce our dependence on rules-of-thumb which have traditionally been used to make models tractable but which have a limited validity. The success of this approach is strongly dependent upon the ability to exploit the synergies between molecular modelling and process engineering, as we have demonstrated in the design of novel processes for carbon dioxide capture from natural gas. Our team of investigators and RAs will be ideally positioned to overcome the challenges posed by high-value products and processes thanks to its current expertise, the investment we have made in breaking down the barriers to interdisciplinary work, and the new skills, continuity and flexibility afforded by a platform grant. An overriding objective of the platform grant is to fast-track the careers of the individual researchers involved. Supporting the careers of researchers has always been central to our approach to research. This grant will give us a unique ability to push this further by providing us with the resources and critical mass to put in place a more structured development programme.