Chemical Shift Tensors of Cimetidine Form A Modeled with Density Functional Theory Calculations: Implications for NMR Crystallography
Chemical Shift Tensors of Cimetidine Form A Modeled with Density Functional Theory Calculations: Implications for NMR Crystallography
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DOI：
10.1021/acs.jpca.0c00421
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发表时间：
2020-04-23
影响因子：
2.9
通讯作者：
Iuliucci, Robbie J.
中科院分区：
文献类型：
--
作者：
Holmes, Sean T.;Engl, Olivia G.;Iuliucci, Robbie J.
用FIREMAT技术测定了活性药物成分甲西咪替丁的十个晶体学上不同的碳原子的C-13化学位移张量的主成分。利用密度泛函理论（DFT）计算了C-13和N-15的磁屏蔽张量，确定了C-13和N-15的峰值。使用平面波和基于簇的方法对西咪替丁和一个有机晶体训练集进行DFT计算。前一组计算允许采用几种结构优化策略，包括使用C-13和N-15磁屏蔽张量参数化色散校正力场的计算。后一组计算的特点是使用资源密集的混合dft方法来计算磁屏蔽张量。使用新的力场校正改进的结构计算结果改善了N-15磁屏蔽张量的值（与实验化学位移张量一致），尽管在C-13屏蔽张量的预测中几乎没有看到改善。用混合泛函计算的C-13和N-15磁屏蔽张量比用GGA泛函计算的结果更符合实验值，与结构精化方法无关；利用杂化DFT方法，碳原子对氮的屏蔽性能得到了显著提高。
The principal components of the C-13 chemical shift tensors for the ten crystallographically distinct carbon atoms of the active pharmaceutical ingredient cimetidine Form A have been measured using the FIREMAT technique. Density functional theory (DFT) calculations of C-13 and N-15 magnetic shielding tensors are used to assign the C-13 and N-15 peaks. DFT calculations were performed on cimetidine and a training set of organic crystals using both plane-wave and cluster-based approaches. The former set of calculations allowed several structural refinement strategies to be employed, includin calculations utilizing a dispersion-corrected force field that was parametrized using C-13 and N-15 magnetic shielding tensors. The latter set of calculations featured the use of resource-intensive hybrid-DFT methods for the calculation of magnetic shielding tensors. Calculations on structures refined using the new force-field correction result in improved values of N-15 magnetic shielding tensors (as gauged by agreement with experimental chemical shift tensors), although little improvement is seen in the prediction of C-13 shielding tensors. Calculations of C-13 and N-15 magnetic shielding tensors using hybrid functionals show better agreement with experimental values in comparison to those using GGA functionals, independent of the method of structural refinement; the shielding of carbon atoms bonded to nitrogen are especially improved using hybrid DFT methods.