Leonov, A. I. et al. (2024) An integrated self-optimizing programmable chemical synthesis and reaction engine. Nature Communications, 15, 1240. (doi: 10.1038/s41467-024-45444-3) (PMID:38336880) (PMCID:PMC10858227)
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Abstract
Robotic platforms for chemistry are developing rapidly but most systems are not currently able to adapt to changing circumstances in real-time. We present a dynamically programmable system capable of making, optimizing, and discovering new molecules which utilizes seven sensors that continuously monitor the reaction. By developing a dynamic programming language, we demonstrate the 10-fold scale-up of a highly exothermic oxidation reaction, end point detection, as well as detecting critical hardware failures. We also show how the use of in-line spectroscopy such as HPLC, Raman, and NMR can be used for closed-loop optimization of reactions, exemplified using Van Leusen oxazole synthesis, a four-component Ugi condensation and manganese-catalysed epoxidation reactions, as well as two previously unreported reactions, discovered from a selected chemical space, providing up to 50% yield improvement over 25–50 iterations. Finally, we demonstrate an experimental pipeline to explore a trifluoromethylations reaction space, that discovers new molecules.
| Item Type: | Articles |
|---|---|
| Additional Information: | The authors gratefully acknowledge financial support from the EPSRC (Grant Nos. EP/L023652/1, EP/R020914/1, EP/S030603/1, EP/R01308X/1, EP/S017046/1, and EP/S019472/1), the ERC (Project No. 670467 SMART-POM), the EC (Project No. 766975 MADONNA), and DARPA (Project Nos. W911NF-18- 2-0036, W911NF-17-1-0316, and HR001119S0003). AJSH acknowledges a scholarship from the Studienstiftung des deutschen Volkes. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Angelone, Dr Davide and Leonov, Mr Artem and Caramelli, Dr Dario and Hammer, Mr Alexander and Khan, Dr Aamir and O'Sullivan, Dr Steven and Mehr, Dr Hessam and Cronin, Professor Lee and Craven, Mr Matthew and Wilbraham, Mr Liam and Lach, Dr Slawomir |
| Authors: | Leonov, A. I., Hammer, A. J.S., Lach, S., Mehr, S. H. M., Caramelli, D., Angelone, D., Khan, A., O'Sullivan, S., Craven, M., Wilbraham, L., and Cronin, L. |
| College/School: | College of Science and Engineering > School of Chemistry |
| Journal Name: | Nature Communications |
| Publisher: | Nature Research |
| ISSN: | 2041-1723 |
| ISSN (Online): | 2041-1723 |
| Copyright Holders: | Copyright © 2024 The Authors |
| First Published: | First published in Nature Communications 15: 1240 |
| Publisher Policy: | Reproduced under a Creative Commons License |
| Data DOI: | 10.5281/zenodo.10326090 |
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