Chemical Reasoning in LLMs

LLM: Large Language Model

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20 papers10 papers in the last four weeks, against 2 the four weeks before. 0.1% of all new papers.

LLMs Depend on Specialist Tools for Out-of-Distribution Generalization in MS/MS Structural Elucidation
Nov 2, 2026Gabriel Asher, Cailum M. K. Stienstra, Tomo Oga +3Chemical Reasoning in LLMs Mass Spectrometry
Matterworks, Inc. Somerville, MA 02143, USA
Cloudra: Geometric Reasoning and Scientific Validation for Autonomous Reaction Mechanism Exploration
Nov 2, 2026Chengyi Yang, Qianxin Zhou, Yang LiChemical Reasoning in LLMs Chemical Reaction Prediction
College of Chemistry and Pharmaceutical Engineering, Changsha University of Science and Technology, Changsha 410114, China · State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China
MOFjson: An Explicit Topological Representation of Metal-Organic Frameworks for Language Models
Oct 25, 2026Anabel Yong, Matthew Hart, Philippe SchwallerMetal-Organic Frameworks Materials Science
Laboratory of Artificial Chemical Intelligence (LIAC), EPFL & National Centre of Competence in Research (NCCR) Separations
Reasoning or Just Prompting? Probing the Mechanism of Latent Chemical Reasoning
Oct 25, 2026Kaiyuan Lu, Jiatong Li, Yatao BianChemical Reasoning in LLMs Implicit Reasoning in Language Models
National University of Singapore
Solvent: Long-Horizon Reasoning for Multi-Step Retrosynthesis
Oct 23, 2026Yifei Wang, Botian Wang, YiFei Wang +8Chemical Reasoning in LLMs Long-Horizon LLM Reasoning
Fudan University · Shanghai Artificial Intelligence Laboratory · Generative Symbolic Intelligence Lab (GenSI), Tsinghua University
Same molecule, Different Knowledge: Cross-Identifier Binding Failures in LLMs For chemistry
Oct 22, 2026Khouloud Saadi, Di WangChemical Language Models Chemical Reasoning in LLMs
Department of Computer Science, King Abdullah University of Science and Technology, KAUST, Thuwal, Saudi Arabia
ReTRACE: Feedback-Guided LLM Agent in a Chemistry Harness for Retrosynthesis Planning
Oct 17, 2026Jinxiang Xie, Yijian Zhang, Qingyuan Yi +2LLM Agents Chemical Reasoning in LLMs
State Key Laboratory of Analytical Chemistry for Life Science, Kuang Yaming Honors School, Chemistry and Biomedicine Innovation Center (ChemBIC), ChemBioMed Interdisciplinary Research Center at Nanjing University, Nanjing University, Nanjing 210023, China · School of Medicine, Guangxi University, Nanning, 530004, China
Distillation, Self-Training, and the Fragility of Learned Chemical Reasoning
Oct 16, 2026Anagha Aneesh, Sebastian Ibarraran, Frank Hu +2Chemical Reasoning in LLMs Chemical Reaction Prediction
Stanford University
MolLean: A Process-Verifiable Language for Chemical Reasoning
Oct 14, 2026Jiatong Li, Yatao BianChemical Reasoning in LLMs Molecular Generation
National University of Singapore
ChemArgus: Automated Scientific Diagnostics for Lab-Grade Multimodal Chemistry Reasoning: A Frontier Benchmark
Oct 14, 2026Hanyao Guo, Mo Cui, Zihan Tan +21Chemical Reasoning in LLMs Scientific Reasoning in Language Models
Beyond Benchmark Accuracy: A Diagnostic Test for LLM Chemical Prediction
Oct 14, 2026Yanyi Su, Yu Zeng, Hongshuai Wang +3Chemical Reasoning in LLMs Retrosynthesis
State Key Laboratory of Physical Chemistry of Solid Surface, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China · DP Technology, Beijing, China
Masked Diffusion Language Agents for Tool-Integrated Chemical Reasoning
Oct 9, 2026Mengdi Liu, Chenghao Jia, Hong Chang +1Chemical Reasoning in LLMs LLM Tool Use
State Key Laboratory of AI Safety, Institute of Computing Technology, CAS, China · University of Chinese Academy of Sciences (CAS), China
Latent JEPA: Abstract Future Prediction for Latent Reasoning in Chemistry
Oct 1, 2026Xinjian Zhao, Yaoyao Xu, Xuemin Chen +2Molecular Optimization Chemical Reasoning in LLMs
School of Data Science, The Chinese University of Hong Kong, Shenzhen · Shanghai Artificial Intelligence Laboratory
ChemOPD: Multi-Teacher On-Policy Distillation for Multi-Task Chemical Reasoning
Sep 27, 2026Yaoyao Xu, Xinjian Zhao, Xiaozhuang Song +2Chemical Reasoning in LLMs Reasoning Distillation
School of Data Science, The Chinese University of Hong Kong, Shenzhen · Shanghai Artificial Intelligence Laboratory
ChemDIRT: A Diversified Instruction, Representation, and Task Benchmark for Robust Chemistry-LLM Evaluation
Aug 21, 2026Eric Inae, Tim Gunn, Chris Bond +1Chemical Reasoning in LLMs LLM Evaluation
University of Notre Dame Notre Dame, Indiana, USA
Chemical Chain-of-Thought Functions as a Hallucination-Prone Molecular Scratchpad
Jul 23, 2026Jiatong Li, Yuxuan Ren, Weida Wang +2CoT Faithfulness Chemical Reasoning in LLMs
Blue Whale Lab, National University of Singapore · Fudan University · Hong Kong Polytechnic University
Grounded verification of chemical and materials reasoning: detection is the bottleneck
Jul 19, 2026Can Polat, Mustafa Kurban, Erchin Serpedin +1LLM Self-Correction LLM Grounding
Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX, USA · Department of Electrical and Computer Engineering, Texas A&M University at Qatar, Doha, Qatar · Department of Prosthetics and Orthotics, Ankara University, Ankara, Turkey +1
From Answers to States: Verifiable Process-Level Evaluation of Chemical Reasoning in Large Language Models
Jun 2, 2026Hongyu Guo, Hao Li, He Cao +2LLM Evaluation Chemical Reasoning in LLMs
Peking University, Shenzhen Graduate School · International Digital Economy Academy (IDEA)
Can Agents Price a Reaction? Evaluating LLMs on Chemical Cost Reasoning
May 8, 2026Yuyang Wu, Yue Huang, Shuaike Shen +8AI Agents for Scientific Discovery LLM Agent Evaluation
Carnegie Mellon University · University of Notre Dame · University of North Carolina, Chapel Hill +1
Coder as Editor: Code-driven Interpretable Molecular Editing
Oct 16, 2025Wenyu Zhu, Chengzhu Li, Xiaohe Tian +8Molecule Design Chemical Reasoning in LLMs
Institute for AI Industry Research, Tsinghua University · Department of Computer Science and Technology, Tsinghua University · School of Pharmaceutical Sciences, Peking University +1

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LLMs Depend on Specialist Tools for Out-of-Distribution Generalization in MS/MS Structural Elucidation

Gabriel Asher, Cailum M. K. Stienstra, Tomo Oga, Devesh Shah Antonio H. de O. Fonseca+2

Matterworks, Inc. Somerville, MA 02143, USA

Chemical Reasoning in LLMs Mass Spectrometry OOD Generalization LLM Tool Use

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A frontier language model was recently reported to solve 1D NMR structural elucidation without tools. We ask whether this capability transfers to tandem mass spectrometry (MS/MS) in the de novo setting, where the model must propose a structure directly from the spectrum without a candidate list or reference library. To separate reasoning from recall, we build a 100-analyte benchmark from MassSpecGym, split by each analyte's textual footprint into in-distribution (well documented in literature) and out-of-distribution (essentially undocumented) arms. We hold the model, harness, and output format fixed and vary only the LLM's access to domain-specific tools. Without tools, a frontier LLM reaches 52% Top-1 accuracy in-distribution but only 2% out-of-distribution. Only access to de novo structure generators improves out-of-distribution accuracy, raising it to as much as 38% Top-1, and the resulting agent outperforms the standalone de novo models both in and out of distribution. These results suggest that LLMs are not effective at de novo MS/MS structural elucidation on their own, and that further gains depend on the specialist tools available to the agent rather than on the LLM itself.