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

arXiv: https://arxiv.org/abs/2608.14720 · HTML: https://mlsanity.com/paper/2608.14720/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 7 of its 44 references that are in the map.
- First posted on arXiv 12 Aug 2026.

## Builds on (most cited first, 7 of 7)

- [DeepSeek-R1: Incentivizing Reasoning Capability in LLMs via Reinforcement Learning](https://mlsanity.com/paper/2501.12948/) (2025)
- [RoFormer: Enhanced Transformer with Rotary Position Embedding](https://mlsanity.com/paper/2104.09864/) (2021)
- [ChemCrow: Augmenting large-language models with chemistry tools](https://mlsanity.com/paper/2304.05376/) (2023)
- [Unraveling Molecular Structure: A Multimodal Spectroscopic Dataset for Chemistry](https://mlsanity.com/paper/2407.17492/) (2024)
- [Accurate and efficient structure elucidation from routine one-dimensional NMR spectra using multitask machine learning](https://mlsanity.com/paper/2408.08284/) (2024)
- [NMR-Solver: Automated Structure Elucidation via Large-Scale Spectral Matching and Physics-Guided Fragment Optimization](https://mlsanity.com/paper/2509.00640/) (2025)
- [NMRGym: A Comprehensive Benchmark for Nuclear Magnetic Resonance Based Molecular Structure Elucidation](https://mlsanity.com/paper/2601.15763/) (2026)

## Abstract (arXiv)

Following the molecular discovery and synthesis revolutions, scalable automated structure elucidation from routine spectroscopic data remains an outstanding challenge. Despite decades of computational efforts, no existing system achieved reliable reasoning over unseen spectra. Here, we propose MACROS, a multi-agent system automating structure elucidation by emulating expert iterative hypothesis-testing. Trained on 100M simulated and 1.6M experimental spectra-molecule pairs, it natively supports arbitrary combinations of routine spectroscopic techniques. It 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 chemical principles rather than memorizing database patterns. MACROS augments chemists via collaboration to deliver sixfold faster, 40% more accurate elucidation. MACROS establishes a scalable foundation for fully automated structure elucidation, and catalyzes accelerated molecular discovery toward autonomous laboratories.