# MAIL: Memory-driven, Adaptive, Incremental, and Literature-grounded Framework for Hypothesis Generation in Chemistry

arXiv: https://arxiv.org/abs/2608.28315 · HTML: https://mlsanity.com/paper/2608.28315/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 29 of its 81 references that are in the map.
- First posted on arXiv 28 Aug 2026.

## Builds on (most cited first, 29 of 29)

- [The Llama 3 Herd of Models](https://mlsanity.com/paper/2407.21783/) (2024)
- [Chain-of-Thought Prompting Elicits Reasoning in Large Language Models](https://mlsanity.com/paper/2201.11903/) (2022)
- [Retrieval-Augmented Generation for Knowledge-Intensive NLP Tasks](https://mlsanity.com/paper/2005.11401/) (2020)
- [Reflexion: Language Agents with Verbal Reinforcement Learning](https://mlsanity.com/paper/2303.11366/) (2023)
- [Tree of Thoughts: Deliberate Problem Solving with Large Language Models](https://mlsanity.com/paper/2305.10601/) (2023)
- [REALM: Retrieval-Augmented Language Model Pre-Training](https://mlsanity.com/paper/2002.08909/) (2020)
- [A Survey on Evaluation of Large Language Models](https://mlsanity.com/paper/2307.03109/) (2023)
- [Flow Network based Generative Models for Non-Iterative Diverse Candidate Generation](https://mlsanity.com/paper/2106.04399/) (2021)
- [Graph Convolutional Policy Network for Goal-Directed Molecular Graph Generation](https://mlsanity.com/paper/1806.02473/) (2018)
- [GFlowNet Foundations](https://mlsanity.com/paper/2111.09266/) (2021)
- [Chain-of-Thought Reasoning Without Prompting](https://mlsanity.com/paper/2402.10200/) (2024)
- [SciMON: Scientific Inspiration Machines Optimized for Novelty](https://mlsanity.com/paper/2305.14259/) (2023)
- [Large Language Models for Automated Open-domain Scientific Hypotheses Discovery](https://mlsanity.com/paper/2309.02726/) (2023)
- [From Automation to Autonomy: A Survey on Large Language Models in Scientific Discovery](https://mlsanity.com/paper/2505.13259/) (2025)
- [MOOSE-Chem: Large Language Models for Rediscovering Unseen Chemistry Scientific Hypotheses](https://mlsanity.com/paper/2410.07076/) (2024)
- [ResearchBench: Benchmarking LLMs in Scientific Discovery via Inspiration-Based Task Decomposition](https://mlsanity.com/paper/2503.21248/) (2025)
- [Multimodal Task Vectors Enable Many-Shot Multimodal In-Context Learning](https://mlsanity.com/paper/2406.15334/) (2024)
- [Large Language Models are Zero Shot Hypothesis Proposers](https://mlsanity.com/paper/2311.05965/) (2023)
- [ChemReasoner: Heuristic Search over a Large Language Model's Knowledge Space using Quantum-Chemical Feedback](https://mlsanity.com/paper/2402.10980/) (2024)
- [Hypothesis Generation for Materials Discovery and Design Using Goal-Driven and Constraint-Guided LLM Agents](https://mlsanity.com/paper/2501.13299/) (2025)
- [Can Large Language Models Unlock Novel Scientific Research Ideas?](https://mlsanity.com/paper/2409.06185/) (2024)
- [Improving Scientific Hypothesis Generation with Knowledge Grounded Large Language Models](https://mlsanity.com/paper/2411.02382/) (2024)
- [Graph-Based Retriever Captures the Long Tail of Biomedical Knowledge](https://mlsanity.com/paper/2402.12352/) (2024)
- [Literature Meets Data: A Synergistic Approach to Hypothesis Generation](https://mlsanity.com/paper/2410.17309/) (2024)
- [Advancing Abductive Reasoning in Knowledge Graphs through Complex Logical Hypothesis Generation](https://mlsanity.com/paper/2312.15643/) (2023)
- [A Survey on Hypothesis Generation for Scientific Discovery in the Era of Large Language Models](https://mlsanity.com/paper/2504.05496/) (2025)
- [MOOSE-Chem2: Exploring LLM Limits in Fine-Grained Scientific Hypothesis Discovery via Hierarchical Search](https://mlsanity.com/paper/2505.19209/) (2025)
- [Stability of Topic Modeling via Matrix Factorization](https://mlsanity.com/paper/1702.07186/) (2017)
- [Retrieval-Retro: Retrieval-based Inorganic Retrosynthesis with Expert Knowledge](https://mlsanity.com/paper/2410.21341/) (2024)

## Abstract (arXiv)

The ever-expanding volume of the chemical literature offers unprecedented opportunities to generate novel and impactful hypotheses. However, the bottleneck lies in efficiently navigating this vast knowledge base to formulate high-quality, experimentally meaningful insights. While Large Language Models (LLMs) show promise for this task, existing methods often rely on static inspiration corpora, predefined heuristics, or laborious human-in-the-loop pipelines and decision-support frameworks that limit scalability and novelty. In this work, we propose an automated approach, a Memory-augmented, Adaptive, Incremental, and Literature-grounded (MAIL) framework for hypothesis generation in chemistry. Our MAIL method formulates hypothesis generation as a temporally grounded, memory-driven reasoning process, where hypotheses emerge from an evolving conceptual path that continuously accumulates and reinterprets prior knowledge. We evaluated the MAIL framework on a public TOMATO-Chem dataset and a newly curated and disseminated high-novelty nature/science challenge (HN-NS) dataset. Across both datasets, MAIL generates structurally coherent and mechanistically plausible hypotheses, achieves the highest MIOS and MPOS by more effectively recovering the central ideas and methodological elements of the historical target hypotheses, and obtains the highest overall expert-evaluation scores for scientific quality. These results demonstrate the potential of LLMs to autonomously explore chemical domains and generate hypotheses that are both innovative and chemically plausible.