Universal Chemical Synthesis and Discovery with 'The Chemputer'

Piotr S. Gromski, Jarosław M. Granda, Leroy Cronin
2019 Trends in Chemistry  
There is a growing drive in the chemistry community to exploit rapidly growing robotic technologies along with artificial intelligence-based approaches. Applying this to chemistry requires a holistic approach to chemical synthesis design and execution. Here, we outline a universal approach to this problem beginning with an abstract representation of the practice of chemical synthesis that then informs the programming and automation required for its practical realization. Using this foundation
more » ... construct closed-loop robotic chemical search engines, we can generate new discoveries that may be verified, optimized, and repeated entirely automatically. These robots can perform chemical reactions and analyses much faster than can be done manually. As such, this leads to a road map whereby molecules can be discovered, optimized, and made on demand from a digital code. Automation in Chemical Synthesis Methodologies for the automation of chemical synthesis, optimization, and discovery have not generally been designed for the realities of laboratory-based research, tending instead to focus on engineering solutions to practical problems. We argue that the potential of rapidly developing technologies (e.g., machine learning and robotics) are more fully realized by operating seamlessly with the way that synthetic chemists currently work ( Figure 1) [1]. This is because the organic chemist often works by thinking backwards as much as they do forwards when planning a synthetic procedure. To reproduce this fundamental mode of operation, a new universal approach to the automated exploration of chemical space is needed that combines an abstraction of chemical synthesis with robotic hardware and closed-loop programming [2,3]. However, this leads chemists to constantly test the reactions with different synthetic parameters and conditions. The alternative to this problem, as shown in this opinion article, is the development of an approach to universal chemistry using a programming language with automation in combination with machine learning and artificial intelligence (AI). Chemists already benefit from algorithms in the field of chemometrics and, therefore, automation is one step forward that might help chemists to navigate and search chemical space more quickly, efficiently, and importantly, without bias. Chemometrics is a field that employs a broad range of algorithms to solve chemistry-related problems and has been well established over the past 50 years [4] . Figure 2 presents a standard chemometrics workflow for processing data. The process begins with data that may be of various formats that depend upon the experiment type and/or posed question. The next step is data preprocessing, which covers a variety of procedures depending on the type of data analyzed (e.g., peak detection, input of missing data, and/or normalization). This process is followed by statistical modeling, which is divided into supervised and unsupervised approaches. Probably one of the most well-known unsupervised approaches is principal component analysis (see Glossary), which allows summarizing large data sets into several components that capture most of the information. Support vector Highlights Recent advances in chemical programming enable adoption and universal automation of chemical discovery and synthesis, combined with artificial intelligence, to efficiently perform laboratory tasks, including the closed-loop data exploration for new reactivity. Robots can perform chemical reactions and analysis much faster than can be done manually, utilizing trial and error, as well as feedback to make autonomous decisions. Chemists can actively seek out to explore chemical space, aiming for discovery of novel or new molecules and reactions using closed-loop robotic chemical search engines.
doi:10.1016/j.trechm.2019.07.004 fatcat:c7ak3odppbcyliv6mp3qa4wi6q