CH--O Hydrogen-Bonds as Structural Elements for Synthesis and Catalysis

Nature has evolved large and complex molecules - proteins - which are comprised of simple building blocks that fold into specific three-dimensional shapes. These folded molecules are important for mediating many physiological chemical reactions. We are interested in examining the weak interactions that hold these molecules in their precise three-dimensional shape, and attempting to replicate them in simple synthetic systems. This involves the design and synthesis of molecules designed to fold into specific shapes, and simulation of their properties using high-level quantum calculation. The insight provided by these calculations will allow us to understand the forces that shape the properties of these small, designed molecules, and will also permit us to potentially emulate the exquisite specificity and reactivity exhibited by natural systems. We hope that this understanding will allow us to develop small, functional molecules that emulate some of the desirable properties of proteins.

We aim to establish a multidisciplinary research program inspired by Nature's ability to selectively and specifically control the formation of complex materials, in order to investigate and understand non-covalent interactions and subsequently exploit this in the development of new functional materials. This project has the potential to make a significant impact across a number of disparate fields in both organic and theoretical chemistry. We propose the union of these two fields in the belief that a fundamental understanding of hydrogen bonding, and the ability to manipulate this phenomenon as a tool is essential in the design of catalysts with enzyme-like reactivity and selectivity. As a consequence, this project has the potential to impact significantly on the fields of foldamer design, and asymmetric catalysis, through the design and synthesis of new materials with valuable catalytic properties. The international collaboration will provide an excellent opportunity for the exchange and transfer of knowledge between synthetic and theoretical groups, providing valuable education and training opportunities for the researchers involved in the project. The multidisciplinary nature of the collaboration will require development of a range of transferable skills, which could be applied in a range of employment sectors leading to greater global competitiveness for UK scientists funded on this research. As such, this work will benefit both the Smith group (through demonstrating the utility of collaboration - especially with theoretical chemists) and the Scheiner group (through the development of methods for validating the utilitg of predicted molecular properties), and the wider academic community in a range of related fields. In the future, this work will benefit synthetic chemists in industry who will be able to utilize the results of our investigations in the design of more efficient and clean chemical reactions, which has an obvious environmental and financial impact. Exploitation of the catalysis aspect of this proposal to broader classes of synthetically useful reactions with enhanced efficiency would translate into a tool of significant utility for researchers in industry and academia. This work could also change our understanding of what is considered to be a 'weak' hydrogen bond, and advance both synthetic and supramolecular chemistry as a consequence. The Department of Chemistry in Oxford is active in outreach activities, and this combination of theory and experiment inspired by Nature would be an excellent topic to engage with the local community who are interested in science. Non-technical lectures aimed at broadening the understanding of this seemingly complex and fundamental work have already been given (as part of a series entitled 'from Nature to Nanotech' at University College in Oxford). The PDRA will have the opportunity to supervise undergraduate students on related projects, which will further disseminate the principles outlined in the proposal thoughout the undegraduate community. We aim to publish the results of our work in high impact international peer reviewed journals (such as Angewandte Chemie and the Journal of the American Chemical Society) and present at international conferences, which will improve the employment prospects and international competitiveness of the UK researchers involved. We also plan to continue to work as a member of EU COST action CM0803 (Foldamers: building blocks, structure and function) to engage and collaborate with other researchers in the field across Europe. This offers an excellent forum for dissemination and networking in a directly relevant field. The effectiveness of this plan for dissemination will be monitored by the PI on a regular basis. Exploitation of any commercially relevant results would be undertaken in conjunction with Oxford Innovation, the intellectual property subsidiary of the University.