MolDeTr: A Chemistry-Informed Deep Learning Model for Next-Generation Automated Analysis of 1H NMR Spectra

Abstract

Accurate interpretation of one-dimensional proton nuclear magnetic resonance (1H NMR) spectra remains a rate-limiting step in molecular structure elucidation, particularly when signal overlap, strong spin coupling, and instrumental distortions mask key features. Existing automated approaches depend on computationally intensive and sensitive iterative quantum-mechanical fitting and still require expert oversight. Here we introduce MolDeTr, a chemistry-informed deep-learning framework derived from the detection-transformer architecture that unifies peak picking, multiplet identification, and extraction of chemical shifts, scalar coupling constants, relaxation-dependent decay times, and proton counts in a single-network pass. The method targets prototypical spin systems of single-component small molecules in 1D 1H NMR, with up to ten distinct groups of chemically equivalent spins (multiplets). MolDeTr is trained exclusively on synthetic spectra generated by spin-dynamics simulations and augmented with realistic experimental artifacts, enabling it to generalize to unseen compounds─including experimental spectra with overlapping and strongly coupled multiplets─without reference standards or prior spin-system knowledge. Unlike structure-conditioned shift-prediction or calculation models, e.g., density functional theory (DFT), that assume the molecular structure is known, MolDeTr addresses the spectrum-conditioned inverse problem and extracts spin-system parameters directly from measured 1D 1H NMR spectra, thereby substantially improving chemical-shift prediction precision by one to 2 orders of magnitude compared to existing structure-conditioned approaches. Benchmarking against a diverse experimental set of 1H NMR spectra of modestly sized small molecules, spanning 80 to 600 MHz base frequency, shows median absolute errors of 0.89 Hz for chemical shifts and 0.20 Hz for coupling constants, while absolute proton counts are predicted with 93.5% accuracy, outperforming state-of-the-art spectrum analysis software and experienced spectroscopists. By eliminating iterative fitting and expert intervention, MolDeTr offers a scalable route to fully automated spectral analysis, accelerating molecular discovery across the chemical sciences.