Improving Chemical Understanding of LLMs via SMILES Parsing

Large language models (LLMs) are increasingly recognized as powerful tools for scientific discovery, particularly in molecular science.A fundamental requirement for these models is the ability to accurately understand molecular structures, commonly encoded in the SMILES representation.However, current LLMs struggle to interpret SMILES, even failing to carry out basic tasks such as counting molecular rings.To address this limitation, we introduce CLEANMOL, a novel framework that formulates SMILES parsing into a suite of clean and deterministic tasks explicitly designed to promote graph-level molecular comprehension.These tasks span from subgraph matching to global graph matching, providing structured supervision aligned with molecular structural properties.We construct a molecular pretraining dataset with adaptive difficulty scoring and pre-train open-source LLMs on these tasks.Our results show that CLEANMOL not only enhances structural comprehension but also achieves the best or competes with the baseline on the Mol-Instructions benchmark. c1ccc(C(F)(F)F)c(N2C(N)=C(C#N)C@HC3=C2CCCC3=O)c1Existence of functional group CC(C)=O?Assemble two fragments?Canonicalize?Length of longest carbon chain?Number of sixmembered rings?(OCC)c([C @H]2C(C#N)=C(N)N (c3ccccc3C(F)(F)F)C3 =C2C(=O)CCC3)c1 CCOc1ccc(OCC)c([C @H]2C(C#N)=C(N)N (c3ccccc3C(F)(F)F)C3 =C2C(=O)CCC3)c1 yes 4 2 Subgraph matching Global graph matching (a) Illustration of SMILES parsing tasks.0.0 0.2 0.4 0.6 0.8 1.0 Accuracy Functional group Ring Chain Canonical Assembly Deepseek-V3-chat GPT-4o CLEANMOL (Ours) (b) Failure of LLMs on SMILES parsing.