# Molecular Representations for Large Language Models

arXiv: https://arxiv.org/abs/2605.01822 · HTML: https://mlsanity.com/paper/2605.01822/

## Key facts

- Cited by 3 papers in the map (data through 14 Oct 2026).
- Builds on 9 of its 31 references that are in the map.
- First posted on arXiv 3 May 2026.

## Builds on (most cited first, 9 of 9)

- [OpenAI GPT-5 System Card](https://mlsanity.com/paper/2601.03267/) (2025)
- [ChemCrow: Augmenting large-language models with chemistry tools](https://mlsanity.com/paper/2304.05376/) (2023)
- [Accelerating scientific discovery with Co-Scientist](https://mlsanity.com/paper/2502.18864/) (2025)
- [Molecular Transformer - A Model for Uncertainty-Calibrated Chemical Reaction Prediction](https://mlsanity.com/paper/1811.02633/) (2018)
- [What can Large Language Models do in chemistry? A comprehensive benchmark on eight tasks](https://mlsanity.com/paper/2305.18365/) (2023)
- [Kosmos: An AI Scientist for Autonomous Discovery](https://mlsanity.com/paper/2511.02824/) (2025)
- [Training a Scientific Reasoning Model for Chemistry](https://mlsanity.com/paper/2506.17238/) (2025)
- [Chemical reasoning in LLMs unlocks strategy-aware synthesis planning and reaction mechanism elucidation](https://mlsanity.com/paper/2503.08537/) (2025)
- [Assessing the Chemical Intelligence of Large Language Models](https://mlsanity.com/paper/2505.07735/) (2025)

## Built on by (most cited first, 3 of 3)

- [Teaching LLMs to See Graphs: Unifying Text and Structural Reasoning](https://mlsanity.com/paper/2605.10247/) (2026)
- [Rethinking Molecular Text Representations for LLMs: An Empirical Study](https://mlsanity.com/paper/2606.03057/) (2026)
- [Strategy-first synthesis planning for complex natural products](https://mlsanity.com/paper/2608.07454/) (2026)

## Abstract (arXiv)

Large Language Models (LLMs) are increasingly being used to support scientific discovery. In chemistry, tasks such as reaction prediction and structure elucidation require reasoning about the structures of molecules. As such, LLM-based systems for chemistry must interact reliably with molecular structures. Most previous studies of LLMs in chemistry have used SMILES strings or IUPAC names as molecular representations; however, the suitability of these formats has not been systematically assessed. In this work, we introduce MolJSON, a novel molecular representation for LLMs, and systematically compare it with five common chemical formats. We evaluated each representation with GPT-5-nano, GPT-5-mini, GPT-5, and Claude Haiku 4.5 using a set of 78,045 questions spanning translation, shortest path, and constrained generation reasoning tasks. We observed substantial variation across representations in the ability of LLMs to interpret and generate molecular graphs, with MolJSON consistently outperforming existing formats. On translation tasks, GPT-5 achieved 71.0% accuracy when converting IUPAC names to MolJSON, compared with 43.7% when converting the same inputs to SMILES. For constrained generation, GPT-5 reached 95.3% accuracy generating MolJSON, compared with 76.3% for IUPAC and 64.0% for SMILES. As an input format for shortest-path reasoning, GPT-5 successfully answered 98.5% of questions with MolJSON, compared with 92.2% for SMILES and 82.7% for IUPAC, whilst also using fewer reasoning tokens. We observed systematic errors associated with atom count and ring complexity for SMILES strings and IUPAC names, whereas MolJSON was more robust to these failure modes. Our results show that the choice of molecular representation has a material impact on LLM performance, and that explicit molecular graph schemas, such as MolJSON, are a promising direction for LLM-based systems in chemistry.