An alternative approach to evaluating the performance of computational methods for predicting chemical shifts is presented. The influence of the theoretical level and basis set on the accuracy in calculating both proton and carbon NMR spectra of a large number of heterocyclic molecules is assessed using a linear regression method, thus omitting the need for a reference (as a potential source of error). The best theoretical levels employed herein (GIAO-PBE0/6-31G(d)//ωB97xD/6-31G(d) or GIAO-ωB97xD/6-31G(d)//ωB97xD/6-31G(d)) approach the accuracy of the most elaborate benchmark-quality calculations. One interesting observation is an unexplained distortion of the derived chemical shifts when an internal reference is used: It leads to larger relative shifts and deviations when the "quality" (size) of the basis set employed is increased. This effect can be corrected by using simple linear regression, but a lack of a systematic correlation between the quality of the basis set and the accuracy of the calculated shifts can still be observed; in fact, very good results can be achieved with modest basis sets. Although the general reliability of this approach needs to be evaluated for other theoretical levels and other substance classes, the abovementioned levels of theory appear robust enough for wider applicability. Graphical Abstract Correlation between computed chemical shieldings and experimental chemical shifts for various heterocyclic compounds.
Keywords: Chemical shift calculations; DFT; Linear regression; Method evaluation; NMR simulation.