Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
J Chem Phys. 2021 Feb 14;154(6):064502. doi: 10.1063/5.0039115.
In this work, the automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) approach was applied to calculate the C and H 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 C 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 H 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 C and H chemical shifts. The employment of diffuse basis functions will further improve the accuracy for C chemical shift calculations, but not for the H 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 C and H 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.
在这项工作中，我们应用自动化碎片量子力学/分子力学（AF-QM/MM）方法来计算分子晶体中的 C 和 H 核磁共振（NMR）化学位移。选择了两个基准分子晶体数据集来计算 NMR 化学位移。我们进行了系统的研究，以检验 AF-QM/MM 计算的收敛性以及不同密度泛函与不同基组对 NMR 化学位移预测的影响。结果表明，当 QM 区域的距离阈值大于 3.5 Å 时，计算的 NMR 化学位移接近收敛。对于 C 化学位移计算，mPW1PW91 泛函是本研究中所选泛函中最好的（即 B3LYP、B3PW91、M06-2X、M06-L、mPW1PW91、OB98 和 OPBE），而 OB98 泛函更适合分子晶体的 H NMR 化学位移预测。此外，使用 B3LYP 泛函，至少需要使用三重ζ基组才能准确重现实验 C 和 H 化学位移。使用弥散基函数将进一步提高 C 化学位移计算的准确性，但对 H 化学位移预测则不然。我们进一步提出了一种将中心分子划分为更小片段的碎片方案。通过与使用整个中心分子作为核心区域的碎片方案结果进行比较，使用分段中心分子的 AF-QM/MM 计算不仅可以获得准确的结果，而且可以降低计算成本。因此，AF-QM/MM 方法能够准确有效地预测分子晶体的 C 和 H NMR 化学位移，并且可以用于处理更复杂的周期性系统，如高分子聚合物和生物大分子。分子晶体的 AF-QM/MM 程序可在 https://github.com/shiman1995/NMR 上获得。
