Selective activation of chemical bonds by active coherent THz spectrometry

'Dial-a-Molecule' is a current EPSRC Grand Challenge. It seeks to tackle questions of the kind: 'How can we reliably predict how to convert one molecule into another?' 'How can we carry out a series of reactions sequentially?' and 'Can we invert modular reactions and/or reactors which can be linked to a myriad of ways to provide complex synthesis?' It has been estimated that achieving the reality of 'Dial-a-Molecule' may take 20 - 40 years to realise. The adventure of this project is to investigate the very real possibility of dramatically bringing this time-frame forward to 5 years distant from now by answering these questions through activation of specific chemical bonds in any given molecule. The consequences of being able to do so would be profound and far-reaching! - new reactions, potential for complete control of outcomes in product synthesis e.g. in C-H activation/oxidation. How can this be done? - by exploiting very recent state-of-the-art developments in electronic engineering to generating high-power terahertz (sub-millimetre wavelength) radiation and to bring it into the world of synthetic organic chemistry. The apparatus that embodies this sophisticated development is called a vector network analyser. Its special features, that are vital to supporting the aims of solving long-standing problems in organic synthesis, is that it generates and receives (phase) stable, widely-tunable radiation spanning many octaves. The resolution in tuning is hyper-fine, being on the order of a million-fold higher than conventional spectrometers (that are broadly based around thermal sources of radiation for their measurement operation). These unique features of the vector-network-analyser offer the potential reality for 'dialing' into the energy required to activate a given chemical bond in a molecule and not, say, an immediate neighbouring bond! Importantly the vector network analyser can be operated to immediately scan the aftermath of a stimulated reaction to investigate what reaction products may have resulted and in what quantity. The activation and scan events may be variably-controlled to range from a second to sub-microsecond time scales as required. An important consequence associated with being able to selectively trigger selective reaction processes with high precision is to eliminate the yield of waste products. Stages in conventional organic synthesis typically yield waste that is 1000s of time the mass of the desired product. Eliminating this waste translates into reduced consumption of energy both in generation and disposal. Over the 18 months of this project the burden of work will be: to design and manufacture a reaction vessel that simultaneously satisfies radiation and chemical constraints; and to systematically trial the programmable capability of the vector network analyser in service of promoting 'dialed' reactions of organic synthesis.

The purpose of this research is to find a new way towards a 'dial a molecule' concept, where new chemicals can be made, not as now by complicated multiple reaction pathways, but designed on a computer and constructed in a reaction vessel by application of specific pulses of electromagnetic energy that promote one reaction pathway over another. As such, these techniques once developed have extensive application in the pharmaceutical, fine-chemical and material processing industries. Our pathways to impact to address opportunities in pharmaceuticals arising from this research will be as follows: a) Dissemination to the industry. We have requested funding to attend a major international conference, well populated by the pharma industry at which we will present our results. In addition, we plan to host at QMUL a joint meeting with the Industrial Chemical KTN on 'dial-a-molecule concepts' at which results from this work will be presented. QMUL will supply the venue for free. QMUL has a strong medical school (the 'Barts & London') and through this we have strong links to all the major drug firms (GSK, AZ, Pfiezzer) and will offer to give a presentation at their research labs seminar series and internally at the B&L as part of a QMUL sponsored 'Discipline Hopping' initiative b) Follow-on-funding to commercialise process. Should this work be successful as we hope, we intend to apply to EPSRC for 'Follow-on-Funding' to take this work forward to show scale up and pharmaceutical applications. The rapid development of high frequency sources means that by the end of the research work, it will be possible to identify sources with greater power and by this point we would have identified the frequency band and power densities required. c) Development of a spin-out company. Once proof-of-concept is established, QMUL has access to funds through its innovation partner, the IP Group, for start-up funds for new companies and we believe a company based on developing equipment for electromagnetic mediated reactions would have great market potential. QMUL is very successful in developing spin-outs; having spun out 8 companies in the last three years and has recently completed a trade sale of one of its spin-outs (Apatech) for over 100M. The fine chemical industry is related to the pharma industry, but its products are more widely used in cosmetics, food, agriculture as well as medical applications. According to the Office of National Statistics show exports of fine chemicals (excluding Pharma) exceeding 6Bn per quarter in late 2009 (http://www.statistics.gov.uk/downloads/theme_economy/Mq1009Q4.pdf). Our pathway to impact for this group will mirror that largely of the pharma industry, but the wide types of products produced (everything from toiletries to perfumes and to specialist pesticide) will make identifying and working with these companies more difficult. Hence QMI Ltd, our business development arm, plans to undertake a study towards the end of the research to identify opportunities where the research undertaken here could be exploited within this sector. QMI have already sold licences to the fine chemical industry for commercialising other technology developed at QMUL, in, for example, micro material handling. QMUL has an extensive Materials and Engineering School that is already working with many large and small companies, such is the aero and automotive sectors, energy generation sectors and semiconductor material sectors. Our pathway to impact here is to engage with the academics in these departments to assess uses for our technology in these fields. In particular, we plan to present at the annual industry day run by this school which is well attended by industry representation. Again a report will be prepared by QMI Ltd at the end of the research to develop targets for commercial exploitation, either by licencing the technology or through spin-outs.