Automated fragmentation quantum mechanical calculation of ¹³C and ¹H chemical shifts in molecular crystals

In this work, the automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) approach was applied to calculate the ¹³C and ¹H nuclear magnetic resonance (NMR) chemical shifts in molecular crystals. Two benchmark sets of molecular crystals were selected to calculate the NMR chemical shifts. Systematic investigation was conducted to examine the convergence of AF-QM/MM calculations and the impact of various density functionals with different basis sets on the NMR chemical shift prediction. The result demonstrates that the calculated NMR chemical shifts are close to convergence when the distance threshold for the QM region is larger than 3.5 Å. For ¹³C chemical shift calculations, the mPW1PW91 functional is the best density functional among the functionals chosen in this study (namely, B3LYP, B3PW91, M06-2X, M06-L, mPW1PW91, OB98, and OPBE), while the OB98 functional is more suitable for the ¹H NMR chemical shift prediction of molecular crystals. Moreover, with the B3LYP functional, at least a triple-ζ basis set should be utilized to accurately reproduce the experimental ¹³C and ¹H chemical shifts. The employment of diffuse basis functions will further improve the accuracy for ¹³C chemical shift calculations, but not for the ¹H chemical shift prediction. We further proposed a fragmentation scheme of dividing the central molecule into smaller fragments. By comparing with the results of the fragmentation scheme using the entire central molecule as the core region, the AF-QM/MM calculations with the fragmented central molecule can not only achieve accurate results but also reduce the computational cost. Therefore, the AF-QM/MM approach is capable of predicting the ¹³C and ¹H NMR chemical shifts for molecular crystals accurately and effectively, and could be utilized for dealing with more complex periodic systems such as macromolecular polymers and biomacromolecules. The AF-QM/MM program for molecular crystals is available at https://github.com/shiman1995/NMR.