利用固体核磁共振缩小利奈唑胺共晶的构象空间

IF 1.8 3区 化学 Q4 CHEMISTRY, PHYSICAL Solid state nuclear magnetic resonance Pub Date : 2022-10-01 DOI:10.1016/j.ssnmr.2022.101813
Mehrnaz Khalaji, Piotr Paluch, Marek J. Potrzebowski, Marta K. Dudek
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引用次数: 3

摘要

许多固体结晶为微晶粉末,因此阻碍了单晶x射线衍射在结构解析中的应用。在这种情况下,联合使用高分辨率固态核磁共振和晶体结构预测(CSP)计算可以取得成功。然而,对于具有显著构象自由度的分子,CSP-NMR协议可能会遇到严重的障碍,包括核磁共振信号分配的模糊性以及计算方法在合理的时间内无法覆盖太宽的构象搜索空间。在这里,我们展示了一种避免这些障碍的可能方法,并在困难的情况下尽可能多地使用这两种方法。在一个简单的案例中,我们的实验导致了宽范围抗生素利奈唑胺(LIN)与2,3-二羟基苯甲酸共晶的晶体结构的阐明,而一个更具挑战性的案例是LIN与2,4-二羟基苯甲酸共晶导致了LIN在晶体内最可能的构象的鉴定。LIN分子有四个可旋转的键,其中一些键可以假设许多离散值,这对确定其在固相中的构象提出了挑战。在我们的工作中,在CSP计算中使用了一组27种构象来产生模型晶体结构,以对照实验固态核磁共振数据进行检查,从而可靠地识别出最可能的分子排列。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Narrowing down the conformational space with solid-state NMR in crystal structure prediction of linezolid cocrystals

Many solids crystallize as microcrystalline powders, thus precluding the application of single crystal X-Ray diffraction in structural elucidation. In such cases, a joint use of high-resolution solid-state NMR and crystal structure prediction (CSP) calculations can be successful. However, for molecules showing significant conformational freedom, the CSP-NMR protocol can meet serious obstacles, including ambiguities in NMR signal assignment and too wide conformational search space to be covered by computational methods in reasonable time. Here, we demonstrate a possible way of avoiding these obstacles and making as much use of the two methods as possible in difficult circumstances. In a simple case, our experiments led to crystal structure elucidation of a cocrystal of linezolid (LIN), a wide-range antibiotic, with 2,3-dihydroxybenzoic acid, while a significantly more challenging case of a cocrystal of LIN with 2,4-dihydroxybenzoic acid led to the identification of the most probable conformations of LIN inside the crystal. Having four rotatable bonds, some of which can assume many discreet values, LIN molecule poses a challenge in establishing its conformation in a solid phase. In our work, a set of 27 conformations were used in CSP calculations to yield model crystal structures to be examined against experimental solid-state NMR data, leading to a reliable identification of the most probable molecular arrangements.

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来源期刊
CiteScore
5.30
自引率
9.40%
发文量
42
审稿时长
72 days
期刊介绍: The journal Solid State Nuclear Magnetic Resonance publishes original manuscripts of high scientific quality dealing with all experimental and theoretical aspects of solid state NMR. This includes advances in instrumentation, development of new experimental techniques and methodology, new theoretical insights, new data processing and simulation methods, and original applications of established or novel methods to scientific problems.
期刊最新文献
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