mlsanityData to 7 Oct 2026

Beyond Chemical QA: Evaluating LLM's Chemical Reasoning with Modular Chemical Operations

arXiv 2505.21318 ↗First posted 27 May 2025cs.AIcited by 46

On the map: LLM reasoning → Clinical and biomedical applications

Abstract (arXiv)

While large language models (LLMs) with Chain-of-Thought (CoT) reasoning excel in mathematics and coding, their potential for systematic reasoning in chemistry, a domain demanding rigorous structural analysis for real-world tasks like drug design and reaction engineering, remains untapped. Current benchmarks focus on simple knowledge retrieval, neglecting step-by-step reasoning required for complex tasks such as molecular optimization and reaction prediction. To address this, we introduce ChemCoTBench, a reasoning framework that bridges molecular structure understanding with arithmetic-inspired operations, including addition, deletion, and substitution, to formalize chemical problem-solving into transparent, step-by-step workflows. By treating molecular transformations as modular "chemical operations", the framework enables slow-thinking reasoning, mirroring the logic of mathematical proofs while grounding solutions in real-world chemical constraints. We evaluate models on two high-impact tasks: Molecular Property Optimization and Chemical Reaction Prediction. These tasks mirror real-world challenges while providing structured evaluability. By providing annotated datasets, a reasoning taxonomy, and baseline evaluations, ChemCoTBench bridges the gap between abstract reasoning methods and practical chemical discovery, establishing a foundation for advancing LLMs as tools for AI-driven scientific innovation.

Key facts. Cited by 46 papers in the map (data through 7 Oct 2026). Placed in Clinical and biomedical applications, one of 17 directions in LLM reasoning. Builds on 44 of its 76 references that are in the map. First posted on arXiv 27 May 2025.

Builds on

44 of 76 references.

Closest ancestors · 4

Same direction, newest first

  1. 2025Chemical reasoning in LLMs unlocks strategy-aware synthesis planning and reaction mechanism elucidation11 Mar
  2. 2025ChemAgent: Self-updating Library in Large Language Models Improves Chemical Reasoning11 Jan
  3. 2024Structural Reasoning Improves Molecular Understanding of LLM8 Oct
  4. 2023Structured Chemistry Reasoning with Large Language Models16 Nov

Other references · 40

  1. 2024The Llama 3 Herd of Modelscited by 14,192
  2. 2021Training Verifiers to Solve Math Word Problemscited by 9,743
  3. 2024DeepSeekMath: Pushing the Limits of Mathematical Reasoning in Open Language Modelscited by 8,851
  4. 2025DeepSeek-R1: Incentivizing Reasoning Capability in LLMs via Reinforcement Learningcited by 6,146
  5. 2021Measuring Mathematical Problem Solving With the MATH Datasetcited by 5,203
  6. 2024Qwen2.5 Technical Reportcited by 4,713
  7. 2024GPT-4o System Cardcited by 4,467
  8. 2024Gemma 2: Improving Open Language Models at a Practical Sizecited by 1,928
  9. 2025s1: Simple test-time scalingcited by 1,311
  10. 2024DeepSeek-Coder: When the Large Language Model Meets Programming -- The Rise of Code Intelligencecited by 1,154
  11. 2024Qwen2.5-Coder Technical Reportcited by 1,151
  12. 2024OlympiadBench: A Challenging Benchmark for Promoting AGI with Olympiad-Level Bilingual Multimodal Scientific Problemscited by 1,099
28 more
  1. 2024Qwen2.5-Math Technical Report: Toward Mathematical Expert Model via Self-Improvementcited by 1,057
  2. 2023Math-Shepherd: Verify and Reinforce LLMs Step-by-step without Human Annotationscited by 895
  3. 2023Gemini: A Family of Highly Capable Multimodal Modelscited by 810
  4. 2024Phi-4 Technical Reportcited by 675
  5. 2025Vision-R1: Incentivizing Reasoning Capability in Multimodal Large Language Modelscited by 653
  6. 2024A Survey on Large Language Models for Code Generationcited by 646
  7. 2023ChemCrow: Augmenting large-language models with chemistry toolscited by 609
  8. 2025VLM-R1: A Stable and Generalizable R1-style Large Vision-Language Modelcited by 515
  9. 2025Visual-RFT: Visual Reinforcement Fine-Tuningcited by 501
  10. 2024LLaVA-CoT: Let Vision Language Models Reason Step-by-Stepcited by 446
  11. 20242 OLMo 2 Furiouscited by 302
  12. 2023SciBench: Evaluating College-Level Scientific Problem-Solving Abilities of Large Language Modelscited by 246
  13. 2024ReFT: Reasoning with Reinforced Fine-Tuningcited by 236
  14. 2025Llama-Nemotron: Efficient Reasoning Modelscited by 151
  15. 2024CodeGemma: Open Code Models Based on Gemmacited by 145
  16. 2024ChemLLM: A Chemical Large Language Modelcited by 100
  17. 2023BioMedGPT: Open Multimodal Generative Pre-trained Transformer for BioMedicinecited by 99
  18. 2024EvaGaussians: Event Stream Assisted Gaussian Splatting from Blurry Imagescited by 56
  19. 20251.4 Million Open-Source Distilled Reasoning Dataset to Empower Large Language Model Trainingcited by 49
  20. 2024Cycle3D: High-quality and Consistent Image-to-3D Generation via Generation-Reconstruction Cyclecited by 36
  21. 2024Are large language models superhuman chemists?cited by 34
  22. 2024Speak-to-Structure: Evaluating LLMs in Open-domain Natural Language-Driven Molecule Generationcited by 22
  23. 2025An Empirical Study of Qwen3 Quantizationcited by 20
  24. 2024MoleculeQA: A Dataset to Evaluate Factual Accuracy in Molecular Comprehensioncited by 19
  25. 2025AE-NeRF: Augmenting Event-Based Neural Radiance Fields for Non-ideal Conditions and Larger Scenecited by 19
  26. 2025Electron flow matching for generative reaction mechanism prediction obeying conservation lawscited by 13
  27. 2024Navigating Chemical-Linguistic Sharing Space with Heterogeneous Molecular Encodingcited by 6
  28. 2025GS2E: Gaussian Splatting is an Effective Data Generator for Event Stream Generationcited by 6

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Cited by year (2026 to 7 Oct)

Citing papers per year: 2025: 14; 2026: 32.

46 papers.

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  1. 2025A Survey of Reinforcement Learning for Large Reasoning Modelscited by 175
  2. 2026Nemotron 3 Ultra: Open, Efficient Mixture-of-Experts Hybrid Mamba-Transformer Model for Agentic Reasoningcited by 32
  3. 2026InternAgent-1.5: A Unified Agentic Framework for Long-Horizon Autonomous Scientific Discoverycited by 24
  4. 2025ChemDFM-R: A Chemical Reasoning LLM Enhanced with Atomized Chemical Knowledgecited by 20
  5. 2025From What to Why: A Multi-Agent System for Evidence-based Chemical Reaction Condition Reasoningcited by 10
  6. 2025Reasoning-Enhanced Large Language Models for Molecular Property Predictioncited by 9
  7. 2025SUPERChem: A Multimodal Reasoning Benchmark in Chemistrycited by 7
  8. 2026LatentChem: From Textual CoT to Latent Thinking in Chemical Reasoningcited by 6
  9. 2026FT-Dojo: Towards Autonomous LLM Fine-Tuning with Language Agentscited by 6
  10. 2026MolClaw: An Autonomous Agent with Hierarchical Skills for Drug Molecule Evaluation, Screening, and Optimizationcited by 6
  11. 2025CoT-Evo: Evolutionary Distillation of Chain-of-Thought for Scientific Reasoningcited by 5
  12. 2026MolecularIQ: Characterizing Chemical Reasoning Capabilities Through Symbolic Verification on Molecular Graphscited by 5
34 more
  1. 2025Atom-anchored LLMs speak Chemistry: A Retrosynthesis Demonstrationcited by 4
  2. 2026Agentic reinforcement learning empowers next-generation chemical language models for molecular design and synthesiscited by 4
  3. 2026MolEvolve: LLM-Guided Evolutionary Search for Interpretable Molecular Optimizationcited by 4
  4. 2025oMeBench: Towards Robust Benchmarking of LLMs in Organic Mechanism Elucidation and Reasoningcited by 3
  5. 2025Breaking the Vicious Cycle: Coherent 3D Gaussian Splatting from Sparse and Motion-Blurred Viewscited by 3
  6. 2025BioMedGPT-Mol: Multi-task Learning for Molecular Understanding and Generationcited by 2
  7. 2026ToxReason: A Benchmark for Mechanistic Chemical Toxicity Reasoning via Adverse Outcome Pathwaycited by 2
  8. 2026Evaluating Relational Reasoning in LLMs with RELcited by 2
  9. 2026LLMZero: Discovering Adaptive Training Strategies for RL Post-Training via LLM Agentscited by 2
  10. 2025Coder as Editor: Code-driven Interpretable Molecular Optimizationcited by 1
  11. 2025MolAct: An Agentic RL Framework for Molecular Editing and Property Optimizationcited by 1
  12. 2026MANGO:Natural Multi-speaker 3D Talking Head Generation via 2D-Lifted Enhancementcited by 1
  13. 2026MolQuest: A Benchmark for Agentic Evaluation of Abductive Reasoning in Chemical Structure Elucidationcited by 1
  14. 2026OmniHuman: A Large-scale Dataset and Benchmark for Human-Centric Video Generationcited by 1
  15. 2026MolViBench: Evaluating LLMs on Molecular Vibe Codingcited by 1
  16. 2026Can Agents Price a Reaction? Evaluating LLMs on Chemical Cost Reasoningcited by 1
  17. 2026Do LLMs Truly Generalize in the Molecular Domain? A Perturbation-Based Analysiscited by 1
  18. 2026Learning Mechanistic Reasoning for Chemical Reactions with Large Language Modelscited by 1
  19. 2026Memory Is Not Always Needed: Characterizing Conditional Memory in Scientific Reasoningcited by 1
  20. 2025Robust Prompt Tuning for Vision-Language Models with Mild Semantic Noisecited by 0
  21. 2025A Scientific Reasoning Model for Organic Synthesis Procedure Generationcited by 0
  22. 2026Deciphering Scientific Reasoning Steps from Outcome Data for Molecule Optimizationcited by 0
  23. 2026Bolek: A Multimodal Language Model for Molecular Reasoningcited by 0
  24. 2026FORGE: Fragment-Oriented Ranking and Generation for Context-Aware Molecular Optimizationcited by 0
  25. 2026MolDeTox: Evaluating Language Model's Stepwise Fragment Editing for Molecular Detoxificationcited by 0
  26. 2026MoleCode unlocks structural intelligence in large language modelscited by 0
  27. 2026From Answers to States: Verifiable Process-Level Evaluation of Chemical Reasoning in Large Language Modelscited by 0
  28. 2026Grounded verification of chemical and materials reasoning: detection is the bottleneckcited by 0
  29. 2026Divergence Decoding: Training-Free Capability Fusioncited by 0
  30. 2026ChemDIRT: A Diversified Instruction, Representation, and Task Benchmark for Robust Chemistry-LLM Evaluationcited by 0
  31. 2026OpenAI4S: Code as Action, Science as Sessionscited by 0
  32. 2026MolDesignBench: Evaluating LLM-based Agent for Scenario-grounded Molecular Designcited by 0
  33. 2026R-GroundBench: A Diagnostic Benchmark for R-Group Groundingin Markush Molecular Editingcited by 0
  34. 2026Latent JEPA: Abstract Future Prediction for Latent Reasoning in Chemistrycited by 0

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  1. 2026TMCS: Tool-Grounded Multi-Agent Reasoning for Compositional Chemical Problem Solving
  2. 2025Bridging the Plausibility-Validity Gap by Fine-Tuning a Reasoning-Enhanced LLM for Chemical Synthesis and Discovery
  3. 2023Monte Carlo Thought Search: Large Language Model Querying for Complex Scientific Reasoning in Catalyst Design
  4. 2025Boosting LLM's Molecular Structure Elucidation with Knowledge Enhanced Tree Search Reasoning
  5. 2026Logos: An evolvable reasoning engine for rational molecular design
  6. 2025Training a Scientific Reasoning Model for Chemistry
  7. 2025ChemATP: A Training-Free Chemical Reasoning Framework for Large Language Models
  8. 2025ChemVTS-Bench: Evaluating Visual-Textual-Symbolic Reasoning of Multimodal Large Language Models in Chemistry