Rapid Structure Determination of Molecular Solids Using Chemical Shifts Directed by Unambiguous Prior Constraints.
Rapid Structure Determination of Molecular Solids Using Chemical Shifts Directed by Unambiguous Prior Constraints.
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DOI：
10.1021/jacs.9b03908
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发表时间：
2019-10-23
影响因子：
15
通讯作者：
Emsley L
中科院分区：
文献类型：
--
作者：
Hofstetter A;Balodis M;Paruzzo FM;Widdifield CM;Stevanato G;Pinon AC;Bygrave PJ;Day GM;Emsley L
基于 NMR 的晶体学方法涉及晶体结构预测方法、从头计算化学位移和固态 NMR 实验的组合，是测定微晶粉末晶体结构的强大方法。然而，目前从固态核磁共振获得的结构信息通常仅在从一组单分子构象开始独立生成一组候选晶体结构后才包含在内。在这里，我们以氨苄西林为例表明，这可能导致结构测定失败。我们提出了一种晶体结构测定方法，其中包括构象异构体选择过程中的实验限制。为了克服晶体样品的实验测量不能明显转化以限制单分子构象空间的问题，我们基于固态NMR相关实验中缺失的交叉峰的分析提出了约束。我们表明，这些缺失为晶体结构和气相构象提供了明确的结构约束，因此可用于明确的选择。该方法针对氟他胺、氟芬那酸和可卡因的晶体结构测定进行了参数化，我们将计算成本降低了约 50%。最重要的是，该方法被证明可以正确确定氨苄西林的晶体结构，而使用当前的方法可能会失败，因为它在晶体结构中采用了高能构象异构体。 NMR 粉末结构的平均位置 RMSE 为 ⟨rav⟩ = 0.176 Å，对应于平均等效位移参数 Ueq = 0.0103 Å2。
NMR-based crystallography approaches involving the combination of crystal structure prediction methods, ab initio calculated chemical shifts and solid-state NMR experiments are powerful methods for crystal structure determination of microcrystalline powders. However, currently structural information obtained from solid-state NMR is usually included only after a set of candidate crystal structures has already been independently generated, starting from a set of single-molecule conformations. Here, we show with the case of ampicillin that this can lead to failure of structure determination. We propose a crystal structure determination method that includes experimental constraints during conformer selection. In order to overcome the problem that experimental measurements on the crystalline samples are not obviously translatable to restrict the single-molecule conformational space, we propose constraints based on the analysis of absent cross-peaks in solid-state NMR correlation experiments. We show that these absences provide unambiguous structural constraints on both the crystal structure and the gas-phase conformations, and therefore can be used for unambiguous selection. The approach is parametrized on the crystal structure determination of flutamide, flufenamic acid, and cocaine, where we reduce the computational cost by around 50%. Most importantly, the method is then shown to correctly determine the crystal structure of ampicillin, which would have failed using current methods because it adopts a high-energy conformer in its crystal structure. The average positional RMSE on the NMR powder structure is ⟨rav⟩ = 0.176 Å, which corresponds to an average equivalent displacement parameter Ueq = 0.0103 Å2.
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影响因子：
56.9
作者：
DEDIOS, AC;PEARSON, JG;OLDFIELD, E
通讯作者：
OLDFIELD, E
影响因子：
6.1
作者：
Gražulis S;Chateigner D;Downs RT;Yokochi AF;Quirós M;Lutterotti L;Manakova E;Butkus J;Moeck P;Le Bail A
通讯作者：
Le Bail A
影响因子：
2.2
作者：
Antzutkin, ON;Lee, YK;Levitt, MH
通讯作者：
Levitt, MH
影响因子：
3.1
作者：
Chierotti, Michele R.;Gobetto, Roberto
通讯作者：
Gobetto, Roberto
影响因子：
15
作者：
Goward, GR;Sebastiani, D;Ishida, H
通讯作者：
Ishida, H