DELTA50: A Highly Accurate Database of Experimental 1H and 13C NMR Chemical Shifts Applied to DFT Benchmarking

Density functional theory (DFT) benchmark studies of H-1 and C-13 NMR chemical shifts often yield differing conclusions, likely due to non-optimal test molecules and non-standardized data acquisition. To address this issue, we carefully selected and measured H-1 and C-13 NMR chemical shifts for 50 structurally diverse small organic molecules containing atoms from only the first two rows of the periodic table. Our NMR dataset, DELTA50, was used to calculate linear scaling factors and to evaluate the accuracy of 73 density functionals, 40 basis sets, 3 solvent models, and 3 gauge-referencing schemes. The best performing DFT methodologies for H-1 and C-13 NMR chemical shift predictions were WP04/6-311++G(2d,p) and omega B97X-D/def2-SVP, respectively, when combined with the polarizable continuum solvent model (PCM) and gauge-independent atomic orbital (GIAO) method. Geometries should be optimized at the B3LYP-D3/6-311G(d,p) level including the PCM solvent model for the best accuracy. Predictions of 20 organic compounds and natural products from a separate probe set had root-mean-square deviations (RMSD) of 0.07 to 0.19 for H-1 and 0.5 to 2.9 for C-13. Maximum deviations were less than 0.5 and 6.5 ppm for H-1 and C-13, respectively.

Automated summary

Density functional theory (DFT) benchmark studies were conducted to evaluate the accuracy of predicting H-1 and C-13 NMR chemical shifts. A carefully selected dataset of 50 small organic molecules was used to assess the performance of different DFT methodologies, basis sets, solvent models, and gauge-referencing schemes. The best results were obtained using WP04/6-311++G(2d,p) and omega B97X-D/def2-SVP for H-1 and C-13 NMR chemical shift predictions, respectively, when combined with the PCM solvent model and GIAO method. Geometries should be optimized at the B3LYP-D3/6-311G(d,p) level including the PCM solvent model for the best accuracy. Predictions for 20 organic compounds and natural products showed good agreement with experimental values, with maximum deviations of less than 0.5 ppm for H-1 and 6.5 ppm for C-13.