DiffSpectra: Molecular Structure Elucidation from Spectra using Diffusion Models

TL;DR

DiffSpectra is a novel diffusion-based framework that accurately infers 2D and 3D molecular structures from multi-modal spectra, integrating geometric and spectral information for de novo elucidation.

Contribution

It introduces the first unified model combining multi-modal spectral reasoning with joint 2D/3D generative modeling for molecular structure elucidation.

Findings

Achieves 40.76% top-1 accuracy in structure prediction

Achieves 99.49% top-10 accuracy, demonstrating high reliability

Highlights the importance of 3D modeling and multi-modal conditioning

Abstract

Molecular structure elucidation from spectra is a fundamental challenge in molecular science. Conventional approaches rely heavily on expert interpretation and lack scalability, while retrieval-based machine learning approaches remain constrained by limited reference libraries. Generative models offer a promising alternative, yet most adopt autoregressive architectures that overlook 3D geometry and struggle to integrate diverse spectral modalities. In this work, we present DiffSpectra, a generative framework that formulates molecular structure elucidation as a conditional generation process, directly inferring 2D and 3D molecular structures from multi-modal spectra using diffusion models. Its denoising network is parameterized by the Diffusion Molecule Transformer, an SE(3)-equivariant architecture for geometric modeling, conditioned by SpecFormer, a Transformer-based spectral encoder capturing multi-modal spectral dependencies. Extensive experiments demonstrate that DiffSpectra accurately elucidates molecular structures, achieving 40.76% top-1 and 99.49% top-10 accuracy. Its performance benefits substantially from 3D geometric modeling, SpecFormer pre-training, and multi-modal conditioning. To our knowledge, DiffSpectra is the first framework that unifies multi-modal spectral reasoning and joint 2D/3D generative modeling for de novo molecular structure elucidation.