Discovering the Solid-State Secrets of Lorlatinib by NMR Crystallography: To Hydrogen Bond or not to Hydrogen Bond
Discovering the Solid-State Secrets of Lorlatinib by NMR Crystallography: To Hydrogen Bond or not to Hydrogen Bond
复制标题
通过 NMR 晶体学发现 Lorlatinib 的固态秘密：氢键或非氢键
DOI：
10.1016/j.xphs.2023.02.022
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发表时间：
2023
影响因子：
3.8
通讯作者：
Rehman Z
中科院分区：
文献类型：
--
作者：
Rehman Z
Lorlatinib是一种用于治疗肺癌的活性药物成分（API）。本文提出了核磁共振晶体学分析，其中单晶x射线衍射结构（CSD: 2205098）测定辅以多核（1H,13C,14/15N,19F）魔角旋转（MAS）固态核磁共振和包括投影仪增强波（GIPAW）计算核磁共振化学位移。Lorlatinib在p21空间基团中结晶，在不对称单元胞中有两个不同的分子，Z ' = 2。四个nh2氢原子中的三个形成分子间氢键，N30-H…N15在两个不同的分子之间，N30-H…O2在两个相等的分子之间。这反映在其中一种NH21H的化学变化明显较低，从4.0 ppm到7.0 ppm。给出了二维1h - 13c、14N-1H和1h（双量子，DQ）-1H（单量子，SQ） MAS NMR谱。分配了1h共振，并确定了与观测到的DQ峰对应的特定h单键h接近度。在1 GHz的拉莫尔频率下，与500或600 MHz相比，分辨率得到了提高。
Lorlatinib is an active pharmaceutical ingredient (API) used in the treatment of lung cancer. Here, an NMR crystallography analysis is presented whereby the single-crystal X-ray diffraction structure (CSD: 2205098) determination is complemented by multinuclear (1H,13C,14/15N,19F) magic-angle spinning (MAS) solid-state NMR and gauge-including projector augmented wave (GIPAW) calculation of NMR chemical shifts. Lorlatinib crystallises in the P21space group, with two distinct molecules in the asymmetric unit cell,Z′ = 2. Three of the four NH2hydrogen atoms form intermolecular hydrogen bonds, N30-H…N15 between the two distinct molecules and N30-H…O2 between two equivalent molecules. This is reflected in one of the NH21H chemical shifts being significantly lower, 4.0 ppm compared to 7.0 ppm. Two-dimensional1H–13C,14N-1H and1H (double-quantum, DQ)-1H (single-quantum, SQ) MAS NMR spectra are presented. The1H resonances are assigned and specific Hsingle bondH proximities corresponding to the observed DQ peaks are identified. The resolution enhancement at a1H Larmor frequency of 1 GHz as compared to 500 or 600 MHz is demonstrated.