Ning Xia

Frazier N. Baker, Daniel Adu-Ampratwum, Reza Averly et al.

Large language model (LLM) agent evaluators leverage specialized tools to ground the rational decision-making of LLMs, making them well-suited to aid in scientific discoveries, such as constrained retrosynthesis planning. Constrained retrosynthesis planning is an essential, yet challenging, process within chemistry for identifying synthetic routes from commercially available starting materials to desired target molecules, subject to practical constraints. Here, we present LARC, the first LLM-based Agentic framework for Retrosynthesis planning under Constraints. LARC incorporates agentic constraint evaluation, through an Agent-as-a-Judge, directly into the retrosynthesis planning process, using agentic feedback grounded in tool-based reasoning to guide and constrain route generation. We rigorously evaluate LARC on a carefully curated set of 48 constrained retrosynthesis planning tasks across 3 constraint types. LARC achieves a 72.9% success rate on these tasks, vastly outperforming LLM baselines and approaching human expert-level success in substantially less time. The LARC framework is extensible, and serves as a first step towards an effective agentic tool or a co-scientist to human experts for constrained retrosynthesis.

Shu Jiang, Zhuosheng Zhang, Hai Zhao et al.

Chemical reaction practicality is the core task among all symbol intelligence based chemical information processing, for example, it provides indispensable clue for further automatic synthesis route inference. Considering that chemical reactions have been represented in a language form, we propose a new solution to generally judge the practicality of organic reaction without considering complex quantum physical modeling or chemistry knowledge. While tackling the practicality judgment as a machine learning task from positive and negative (chemical reaction) samples, all existing studies have to carefully handle the serious insufficiency issue on the negative samples. We propose an auto-construction method to well solve the extensively existed long-term difficulty. Experimental results show our model can effectively predict the practicality of chemical reactions, which achieves a high accuracy of 99.76\% on real large-scale chemical lab reaction practicality judgment.