Rehman Zainab, Lubay Jairah, Franks W Trent, Bartók Albert P, Corlett Emily K, Nguyen Bao, Scrivens Garry, Samas Brian M, Frericks-Schmidt Heather, Brown Steven P
Department of Physics, University of Warwick, Coventry, CV4 7AL, UK.
Warwick Centre for Predictive Modelling, School of Engineering, University of Warwick, Coventry, CV4 7AL, UK.
Faraday Discuss. 2025 Jan 8;255(0):222-243. doi: 10.1039/d4fd00088a.
The application of NMR crystallography to organic molecules is exemplified by two case studies. For the tosylate salt of the active pharmaceutical ingredient, Ritlectinib, solid-state NMR spectra are presented at a H Larmor frequency of 1 GHz and a magic-angle spinning (MAS) frequency of 60 kHz. Specifically, N-H heteronuclear multiple-quantum coherence (HMQC) and H-H double-quantum (DQ) single-quantum (SQ) correlation experiments are powerful probes of hydrogen bonding interactions. A full assignment of the H, C and N/N chemical shifts is achieved using also H-C cross polarization (CP) HETCOR spectra together with gauge-including projector augmented wave (GIPAW) DFT calculation for the geometry-optimised X-ray diffraction crystal structure that is reported here (CCDC 2352028). In addition, GIPAW calculations are presented for the C chemical shifts in the two polymorphs of cellulose for which diffraction structures are available. For both case studies, a focus is on the discrepancy between experiment and GIPAW calculation.
两个案例研究例证了核磁共振晶体学在有机分子中的应用。对于活性药物成分瑞特替尼的甲苯磺酸盐，给出了在1 GHz的氢拉莫尔频率和60 kHz的魔角旋转（MAS）频率下的固态核磁共振谱。具体而言，N-H异核多量子相干（HMQC）和H-H双量子（DQ）单量子（SQ）相关实验是氢键相互作用的有力探测手段。结合本文报道的几何优化X射线衍射晶体结构（CCDC 2352028）的含规范投影增强波（GIPAW）密度泛函理论（DFT）计算，利用H-C交叉极化（CP）异核化学位移相关（HETCOR）谱实现了对H、C和N/N化学位移的完全归属。此外，还给出了两种具有衍射结构的纤维素多晶型物中C化学位移的GIPAW计算结果。对于这两个案例研究，重点均在于实验与GIPAW计算之间的差异。
