Reaction Templates: Bridging Synthesis Knowledge and Artificial Intelligence.

ABSTRACT

ConspectusThe field of chemical research boasts a long history of developing software to automate synthesis planning and reaction prediction. Early software relied heavily on expert systems, requiring significant effort to encode vast amounts of synthesis knowledge into a computer-readable format. However, recent advancements in deep learning have shifted the focus toward AI models, offering improved prediction capabilities. Despite these advancements, current AI models often lack the integration of known synthesis rules and intuitions, creating a gap that hinders interpretability and future development of the models. To bridge them, our research group has been actively working on incorporating reaction templates into deep learning models, achieving promising results across various applications.In this Account, we present our latest works to incorporate the known synthesis knowledge into the deep learning models through the utilization of reaction templates. We begin by highlighting the limitations of early computer programs heavily reliant on hand-coded rules. These programs, while providing a foundation for the field, presented limitations in scalability and adaptability. We then introduce SMARTS (SMILES arbitrary target specification), a popular Python-readable format for representing chemical reactions. This format of reaction encoding facilitates the quick integration of synthesis knowledge into AI models built using the Python language. With the SMARTS-based reaction templates, we introduce our recent efforts of developing an AI model for reaction-based molecule optimization. Subsequently, we discuss the recent efforts to automate the extraction of reaction templates from vast chemical reaction databases. This approach eliminates the previously required manual effort of encoding knowledge, a process that could be time-consuming and prone to error when dealing with large data sets. By customizing the automated extraction algorithm, we have developed powerful AI models for specific tasks such as retrosynthesis (LocalRetro), reaction outcome prediction (LocalTransform), and atom-to-atom mapping (LocalMapper). These models, aligned with the intuition of chemists, demonstrate the effectiveness of incorporating reaction templates into deep learning frameworks.Looking toward the future, we believe that utilizing reaction templates to connect known chemical knowledge and AI models holds immense potential for various applications. Not only can this approach significantly benefit future AI models focused on challenging tasks like reaction mechanism labeling and prediction, but we anticipate it can also extend its reach to the realm of inorganic synthesis. By integrating synthesis knowledge, we can not only achieve improved performance but also enhance the interpretability of AI models, paving the way for further advancements in AI-powered chemical synthesis.