Multi-Agent Closed-Loop Reasoning for Organic Structure Elucidation from Multimodal Spectra

Summary

Automated structure elucidation from routine spectroscopy remains a major challenge. Researchers introduce MACROS, a multi-agent system that emulates expert iterative hypothesis testing. Trained on 100 million simulated and 1.6 million experimental spectra-molecule pairs, it natively supports arbitrary combinations of routine spectroscopic techniques and achieves unprecedented zero-shot generalization to diverse real-world samples, correctly identifying synthetic compounds, natural products, and metabolites above 500 Da with 1D NMR. Remarkably, MACROS spontaneously recovers textbook spectroscopic correlations from unassigned data and exhibits emergent chemical intuition such as a ring-first parsing preference, learning fundamental principles rather than memorizing database patterns. When collaborating with chemists, it delivers sixfold faster and 40% more accurate elucidation, establishing a scalable foundation for fully automated structure elucidation and accelerating molecular discovery toward autonomous laboratories.