Crystal Structure of Nilotinib Hydrochloride Monohydrate According to Powder X-Ray Diffraction Data

IF 1.2 4区化学 Q4 CHEMISTRY, INORGANIC & NUCLEAR

Journal of Structural Chemistry Pub Date : 2024-04-30 DOI:10.1134/s0022476624030132

A. S. Goloveshkin, E. S. Kulikova, R. A. Novikov, A. V. Vologzhanina, A. A. Korlyukov

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Abstract

The crystal structure of nilotinib hydrochloride monohydrate, being an active pharmaceutical substance of the drug Tasigna for chronic myeloid leukemia, is determined by powder X-ray diffraction (XRD) using a synchrotron radiation source of the National Research Center “Kurchatov Institute”. The molecular conformation of the cation in the crystal differs from that in the initial nilotinib molecule and its solvates due to the rotation of substituents about single C–N, C–O, and C–C bonds. In the crystal, the nilotinib molecule is protonated at the nitrogen atom of the imidazolium heterocycle and involved in the N–H…N, N–H…O, and N–H…Cl hydrogen bonds with another cation, water molecule, and anion respectively. The resulting structure is determined with high accuracy. Errors in bond lengths are only slightly worse than those for the structures determined from single crystal XRD data. In addition, one of the best values of the half uncertainty window (HUW) is achieved in the refinement. The importance of this parameter is considered in the article. The structure agrees with the solid-state NMR data. The comparison of the results with the solution NMR spectroscopy data reveals noticeable changes in the nilotinib molecular structure during crystallization.

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根据粉末 X 射线衍射数据确定的盐酸尼罗替尼一水合物晶体结构

摘要利用 "库尔恰托夫研究所 "国家研究中心的同步辐射源，通过粉末 X 射线衍射（XRD）测定了盐酸尼罗替尼一水合物的晶体结构，该晶体是治疗慢性髓性白血病的药物 Tasigna 的活性药物物质。由于取代基围绕单个 C-N、C-O 和 C-C 键旋转，晶体中阳离子的分子构象与初始尼洛替尼分子及其溶质中的分子构象不同。在晶体中，尼洛替尼分子在咪唑杂环的氮原子上质子化，并分别与另一个阳离子、水分子和阴离子形成 N-H...N、N-H...O 和 N-H...Cl 氢键。由此确定的结构精确度很高。键长误差仅略低于根据单晶 XRD 数据确定的结构。此外，在细化过程中还获得了半不确定窗口（HUW）的最佳值之一。文章考虑了这一参数的重要性。该结构与固态核磁共振数据一致。将结果与溶液核磁共振光谱数据进行比较后发现，尼洛替尼分子结构在结晶过程中发生了明显变化。

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来源期刊

Journal of Structural Chemistry 化学-无机化学与核化学

CiteScore

1.60

自引率

12.50%

发文量

142

审稿时长

8.3 months

期刊介绍： Journal is an interdisciplinary publication covering all aspects of structural chemistry, including the theory of molecular structure and chemical bond; the use of physical methods to study the electronic and spatial structure of chemical species; structural features of liquids, solutions, surfaces, supramolecular systems, nano- and solid materials; and the crystal structure of solids.