Leonov Artem I, Hammer Alexander J S, Lach Slawomir, Mehr S Hessam M, Caramelli Dario, Angelone Davide, Khan Aamir, O'Sullivan Steven, Craven Matthew, Wilbraham Liam, Cronin Leroy
School of Chemistry, The University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK.
Nat Commun. 2024 Feb 9;15(1):1240. doi: 10.1038/s41467-024-45444-3.
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.
用于化学的机器人平台正在迅速发展，但目前大多数系统尚无法实时适应不断变化的情况。我们展示了一种动态可编程系统，该系统能够制造、优化和发现新分子，它利用七个传感器持续监测反应。通过开发一种动态编程语言，我们展示了一个高度放热氧化反应的10倍放大规模、终点检测以及关键硬件故障检测。我们还展示了如何将高效液相色谱、拉曼光谱和核磁共振等在线光谱技术用于反应的闭环优化，以范勒森恶唑合成、四组分乌吉缩合反应和锰催化环氧化反应为例，以及从选定化学空间中发现的两个先前未报道的反应，在25至50次迭代中收率提高了50%。最后，我们展示了一个用于探索三氟甲基化反应空间的实验流程，该流程发现了新分子。
