Practical Machine Learning Strategies 4: Using Neural Networks to Replicate Proton and C NMR Chemical Shifts Obtained from ωB97X-D/6-31G* Density Functional Calculations.
Journal:
The Journal of organic chemistry
Published Date:
Aug 5, 2025
Abstract
Described are neural networks that accurately reproduce proton and C chemical shifts obtained from ωB97X-D/6-31G*//ωB97X-D/6-31G* density functional model GIAO calculations. They support uncharged, closed-shell molecules comprising H, C, N, O, F, S, Cl, and Br. Development involved training to ≈2.7 million equilibrium geometry and chemical shift calculations for a diverse collection of organic molecules (including synthetic drugs and natural products). Referenced to ωB97X-D/6-31G*//ωB97X-D/6-31G* calculations, chemical shifts from neural networks for 601 marine natural products show RMS errors of 0.05 ppm (proton) and 0.76 ppm (C). RMS errors of 0.09 ppm (proton) and 1.02 ppm (C) shifts result when equilibrium geometries from a previously described "estimated ωB97X-D/6-31G*" neural network model (trained to reproduce ωB97X-D/6-31G* geometries) are utilized. A second assessment of experimental C chemical shifts for 246 natural products is provided. Using neural network models to provide both geometries and chemical shifts: 45% of C shifts reproduce experimental values within 1 ppm, 73% within 2 ppm, and 86% within 3 ppm. Utilizing neural network models for both equilibrium geometries and chemical shifts reduces the computational time required for accurate proton and C chemical shifts from tens to hundreds of minutes to just a few seconds per molecule.
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