In-Context Molecular Property Prediction with LLMs: A Blinding Study on Memorization and Knowledge Conflicts
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Abstract (arXiv)
The capabilities of large language models (LLMs) have expanded beyond natural language processing to scientific prediction tasks, including molecular property prediction. However, their effectiveness in in-context learning remains ambiguous, particularly given the potential for training data contamination in widely used benchmarks. This paper investigates whether LLMs perform genuine in-context regression on molecular properties or instead rely on verbatim retrieval of memorized target values. Furthermore, we analyze the interplay between pre-trained knowledge and in-context information through a series of progressively blinded experiments. We evaluate nine LLM variants across three families (GPT-4.1, GPT-5, Gemini 2.5) on three MoleculeNet datasets (Delaney solubility, Lipophilicity, QM7 atomization energy) using a systematic blinding approach that iteratively reduces available information, complemented by 0-, 60-, and 1000-shot in-context sample sizes as an additional control for information access. To validate the memorization analysis and the blinding experiments, we add a positive and a negative control for the memorization experiments and structural reference baselines for the multi-shot experiments as well as bootstrap confidence intervals for all results. We find no evidence of verbatim retrieval on the legacy benchmarks and show that blinding exposes conflicts between pre-trained knowledge and in-context information. This work provides a principled framework for evaluating molecular property prediction under controlled information access.
Key facts. Cited by 2 papers in the map (data through 7 Oct 2026). Builds on 15 of its 36 references that are in the map. First posted on arXiv 26 Mar 2026.
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15 of 36 references.
References · 15
- 2020Language Models are Few-Shot Learnerscited by 32,199
- 2022Chain-of-Thought Prompting Elicits Reasoning in Large Language Modelscited by 12,302
- 2017Neural Message Passing for Quantum Chemistrycited by 3,460
- 2023Lost in the Middle: How Language Models Use Long Contextscited by 3,383
- 2017MoleculeNet: A Benchmark for Molecular Machine Learningcited by 1,037
- 2022Quantifying Memorization Across Neural Language Modelscited by 755
- 2022What learning algorithm is in-context learning? Investigations with linear modelscited by 671
- 2023ChemCrow: Augmenting large-language models with chemistry toolscited by 609
- 2019Analyzing Learned Molecular Representations for Property Predictioncited by 373
- 2023NLP Evaluation in trouble: On the Need to Measure LLM Data Contamination for each Benchmarkcited by 339
- 2023What can Large Language Models do in chemistry? A comprehensive benchmark on eight taskscited by 179
- 2024ChemLLM: A Chemical Large Language Modelcited by 100
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