# Masked Diffusion Language Agents for Tool-Integrated Chemical Reasoning

arXiv: https://arxiv.org/abs/2610.13330 · HTML: https://mlsanity.com/paper/2610.13330/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Medical and scientific domain agents, one of 16 directions in LLM agents and tool use.
- Builds on 35 of its 47 references that are in the map.
- First posted on arXiv 9 Oct 2026.

## Placed in

- LLM agents and tool use / [Medical and scientific domain agents](https://mlsanity.com/agents/medical-and-scientific-domain-agents/)

## Builds on (most cited first, 30 of 35)

- [ReAct: Synergizing Reasoning and Acting in Language Models](https://mlsanity.com/paper/2210.03629/) (2022)
- [A Survey on Large Language Model based Autonomous Agents](https://mlsanity.com/paper/2308.11432/) (2023)
- [Structured Denoising Diffusion Models in Discrete State-Spaces](https://mlsanity.com/paper/2107.03006/) (2021)
- [Large Language Diffusion Models](https://mlsanity.com/paper/2502.09992/) (2025)
- [Simple and Effective Masked Diffusion Language Models](https://mlsanity.com/paper/2406.07524/) (2024)
- [ChemCrow: Augmenting large-language models with chemistry tools](https://mlsanity.com/paper/2304.05376/) (2023)
- [Simplified and Generalized Masked Diffusion for Discrete Data](https://mlsanity.com/paper/2406.04329/) (2024)
- [Dream 7B: Diffusion Large Language Models](https://mlsanity.com/paper/2508.15487/) (2025)
- [A Continuous Time Framework for Discrete Denoising Models](https://mlsanity.com/paper/2205.14987/) (2022)
- [Improve Mathematical Reasoning in Language Models by Automated Process Supervision](https://mlsanity.com/paper/2406.06592/) (2024)
- [Block Diffusion: Interpolating Between Autoregressive and Diffusion Language Models](https://mlsanity.com/paper/2503.09573/) (2025)
- [Your Absorbing Discrete Diffusion Secretly Models the Conditional Distributions of Clean Data](https://mlsanity.com/paper/2406.03736/) (2024)
- [rStar-Math: Small LLMs Can Master Math Reasoning with Self-Evolved Deep Thinking](https://mlsanity.com/paper/2501.04519/) (2025)
- [LLaDA 1.5: Variance-Reduced Preference Optimization for Large Language Diffusion Models](https://mlsanity.com/paper/2505.19223/) (2025)
- [Mercury: Ultra-Fast Language Models Based on Diffusion](https://mlsanity.com/paper/2506.17298/) (2025)
- [Seed Diffusion: A Large-Scale Diffusion Language Model with High-Speed Inference](https://mlsanity.com/paper/2508.02193/) (2025)
- [LLaDA2.0: Scaling Up Diffusion Language Models to 100B](https://mlsanity.com/paper/2512.15745/) (2025)
- [Concrete Score Matching: Generalized Score Matching for Discrete Data](https://mlsanity.com/paper/2211.00802/) (2022)
- [Fast-dLLM v2: Efficient Block-Diffusion LLM](https://mlsanity.com/paper/2509.26328/) (2025)
- [SDAR: A Synergistic Diffusion-AutoRegression Paradigm for Scalable Sequence Generation](https://mlsanity.com/paper/2510.06303/) (2025)
- [LlaSMol: Advancing Large Language Models for Chemistry with a Large-Scale, Comprehensive, High-Quality Instruction Tuning Dataset](https://mlsanity.com/paper/2402.09391/) (2024)
- [A Review of Large Language Models and Autonomous Agents in Chemistry](https://mlsanity.com/paper/2407.01603/) (2024)
- [SciAgent: Tool-augmented Language Models for Scientific Reasoning](https://mlsanity.com/paper/2402.11451/) (2024)
- [SciToolAgent: A Knowledge Graph-Driven Scientific Agent for Multi-Tool Integration](https://mlsanity.com/paper/2507.20280/) (2025)
- [CACTUS: Chemistry Agent Connecting Tool-Usage to Science](https://mlsanity.com/paper/2405.00972/) (2024)
- [Structured Chemistry Reasoning with Large Language Models](https://mlsanity.com/paper/2311.09656/) (2023)
- [MT-Mol:Multi Agent System with Tool-based Reasoning for Molecular Optimization](https://mlsanity.com/paper/2505.20820/) (2025)
- [CheMatAgent: Enhancing LLMs for Chemistry and Materials Science through Tree-Search Based Tool Learning](https://mlsanity.com/paper/2506.07551/) (2025)
- [Testing GPT-4 with Wolfram Alpha and Code Interpreter plug-ins on math and science problems](https://mlsanity.com/paper/2308.05713/) (2023)
- [From What to Why: A Multi-Agent System for Evidence-based Chemical Reaction Condition Reasoning](https://mlsanity.com/paper/2509.23768/) (2025)

## Abstract (arXiv)

Designing tool-integrated reasoning agent systems for complex chemical tasks remains a fundamental challenge. Although recent chemical agents have demonstrated promising performance through the integration of external tools, they are still built on the autoregressive paradigm, which is inherently constrained by causal attention and left-to-right generation. As a result, they often struggle with bidirectional molecular understanding, global coordinated tool planning and multi-source evidence integration. To address this challenge, we introduce ChemDiffAgent, the first masked diffusion language agent for tool-integrated chemical reasoning. It reformulates chemical reasoning as iterative denoising over interleaved reasoning and tool-use trajectories, enabling tool-use decisions to be jointly determined under full-trajectory context and thereby better aligning the agent's decision boundary with its knowledge boundary. We further analyze how this paradigm benefits agentic reasoning through harder infilling subproblems during training and flexible arbitrary-order decoding during inference. Then we develop a two-stage post-training framework, comprising agentic supervised fine-tuning and variance-reduced preference optimization, to enhance tool-use and reasoning capabilities. We also construct a comprehensive benchmark covering six chemistry tasks across both single-turn and multi-turn tool-use scenarios. Under matched budgets and evaluation, ChemDiffAgent consistently outperforms autoregressive agents, achieving an overall improvement of approximately 20%. Notably, our 8B model achieves performance comparable to, in some cases surpassing, significantly larger frontier models, such as GPT 5.5 and Claude Opus 4.7. Code is available at https://github.com/bilemond/ChemDiffAgent.