More and more, chemistry is taking advantage of the technological revolution that has taken place over the last 20 years. For example, automation of what were once seen as manual procedures can now be routinely carried out 24/7 without the need for an operator to be present. As a consequence, increasingly large amounts of data are routinely generated in chemistry labs on a day-to-day basis. The result is the chemist of today has access to far more data than ever before, but, to transform this raw data into useful information, knowledge of both chemistry and statistical methods is required.
The Dial-a-Molecule vision
The overall vision of Dial-a-Molecule is that “in 20-40 years, scientists will be able to deliver any desired molecule within a timeframe useful to the end-user, using safe, economically viable and sustainable processes.”
In 2012, the Roadmap for Synthesis in the 21st Century was published by the EPSRC Dial-a-Molecule Grand Challenge Network. Under the “Lab of the Future” Theme, the Roadmap stated that “the use of Design of Experiments and other statistical methods for reaction optimization is well established in process chemistry, or in an industrial setting, but little used in small scale ‘discovery’ chemistry (e.g. academic research labs), often because of the overhead imposed by its use and the unfamiliarity of the technique”. It went onto propose “in the short term, a priority should be to increase the familiarity of synthetic chemists with the techniques used in process chemistry and process engineering”. Although DoE and statistical methods won’t solve Dial-a-Molecule, “embedding DoE and other statistical methods into PG training is important to develop the generation of chemists who will be responsible for developing the Dial-a-Molecule idea.”
Statistical methods alone won’t solve Dial-a-Molecule, but a community that understands how and when to apply DoE (and other methods such as Principal Components Analysis) will be able to derive understanding and hasten the extrapolation of preliminary results to usable processes through, amongst other things, routine investigation (and understanding) of reproducibility, study of reaction parameters and accelerated discovery of ‘unexpected’ reaction factors (e.g. role of impurities, unexpected synergies or interactions).
Progress towards this vision:
Working towards achieving these goals, Dial-a-Molecule has organized two community events on “Experimental Design: An Essential Skill for Chemists”. The first of these was held on 12 May 2014 (Burlington House, Royal Society of Chemistry, London) and brought together 33 members of the community to gain an appreciation of the current state of the art (e.g. what the situation is throughout UK HEI’s, resources available, what the gaps are) and find a way forward. The following aims were defined:
- Embed statistical methods into mainstream academic chemistry courses and research so that all chemistry graduates (PG and UG) have a grounding in statistics and the basic role it has in chemistry.
- Establish a community of practice or an RSC Specialist Interest Group to share learnings, best practice and new applications.
- Provide a solution that is self-sustaining by building a cohort of experts, regionally available to conduct face-to-face training, or act as mentors.
From this meeting, 2 small grants were awarded to prepare UG lab modules (theoretical and practical):
- R. Bourne, J. Blacker and B. Taylor (AstraZeneca) – Improving Reaction Efficiency through Design of Experiments using Flow Processing (developing an UG lab module to introduce chemistry students to DoE)
- P. Allan, A. Nordon and C. Jamieson (University of Strathclyde) – Staged dataset for design of experiments (DoE)
Following a call, four small grants were awarded to research/academic collaborations with the aim of providing academic examples of where statistical methods have enhanced chemistry research.
- T. Sheppard (UCL) and P. Murray (Catalysis Consulting Ltd) – Construction of a publicly available solvent PCA map for optimizing chemical reactions in academic laboratories
- C. E. Willans (University of Leeds), B. N. Nguyen (University of Leeds), N. Fey (University of Bristol) and S. Tyler (CatScI Ltd) – Descriptor-led Screening of NHC Ligands
- A. Malkov (Loughborough University) and N. Fey (University of Bristol) – Ligand-directed Selectivity in Copper-catalysed Allylic Amination
- R. Bourne (University of Leeds), B. Taylor (AstraZeneca), R. Woodward (AstraZeneca), R. Meadows (AstraZeneca) and N. Holmes (University of Leeds)
Summaries of the projects can be accessed by clicking on the links.
An outline syllabus for an UG taught module is also in development and a proposal for an introductory textbook aimed at chemists has been accepted.
Updates on the progress of these mini-projects were presented at the second community event held on 8 December 2014, along with a very thought provoking key-note seminar from Prof John MacInnes (University of Edinburgh), the Strategic Advisor for Quantitative Methods to the ESRC. In his talk, he outlined the drive for, and issues the Social Sciences faced in implementing, Quantitative Training, how they went about it (Q-Step Centres), and the success and culture change they have witnessed in the following years. The consensus drawn from the meeting was “If Social Sciences can do it, why can’t we?”
Looking into the future:
Since the initiative began, Dial-a-Molecule has been engaging with important stakeholders such as the RSC, Nuffield Foundation, EPSRC, HEFCE, IChemE, the British Academy, Cogent Skills and the Economic and Social Research Council (ESRC) via their Strategic Advisor for Quantitative Methods Training. Following the success in the Social Sciences arena, we have been developing a proposal to present to the EPSRC/HEFCE to request funding for the formal establishment of provincial centres of excellence with expertise in the application of statistical methods to Chemistry Research and to appoint a Strategic Advisor. In the meantime we have been building on the expertise already available in a small number of HEIs and have been supporting further development and roll-out of the lab modules.
Although the Dial-a-Molecule Network has formally come to a conclusion, work is still continuing in this area. If you are interested in knowing more, or becoming involved, please contact Gill Smith.