Solid-state NMR analysis of a complex crystalline phase of ronacaleret hydrochloride.
Solid-state NMR analysis of a complex crystalline phase of ronacaleret hydrochloride.
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盐酸 ronacaleret 复杂晶相的固态 NMR 分析。
DOI：
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发表时间：
2014
影响因子：
3.3
通讯作者：
R. Copley
中科院分区：
文献类型：
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作者：
F. Vogt;G. Williams;M. Strohmeier;Matthew N. R. Johnson;R. Copley
通过固态核磁共振（SSNMR）光谱和单晶X射线衍射研究了药物化合物盐酸罗那卡莱的晶相。晶体结构被确定为在不对称单元中包含两个独立的阳离子分子和氯阴离子，其与分子的共价结构联合收割机结合以产生复杂的SSNMR谱。实验方法的基础上偶极相关，化学位移张量分析，和四极相互作用分析，以获得有关此阶段的详细信息。密度泛函理论（DFT）计算用于预测化学屏蔽和电场梯度（EFG）参数与实验进行比较。(1)H SSNMR实验在16.4 T使用魔角自旋（MAS）和homopolar偶极去耦提供有关氢键和分子连接性，可以与晶体结构的信息。(19)F（13）Z' = 2结构的C归属是用DFT计算、（19）F同偶极相关和（13）C-（19）F异偶极相关实验得到的。（35）16.4 T的Cl MAS实验观察到使用计算的化学屏蔽和EFG参数指定的两个氯位点。SSNMR偶极相关实验用于提取许多感兴趣位置的（1）H-（13）C、（1）H-（15）N、（1）H-（19）F、（13）C-（19）F和（1）H-（35）Cl贯穿空间的连接性信息。结果允许一套SSNMR实验和计算方法的性能评估，适用于一个复杂的，但典型的药物固相。
A crystalline phase of the pharmaceutical compound ronacaleret hydrochloride is studied by solid-state nuclear magnetic resonance (SSNMR) spectroscopy and single-crystal X-ray diffraction. The crystal structure is determined to contain two independent cationic molecules and chloride anions in the asymmetric unit, which combine with the covalent structure of the molecule to yield complex SSNMR spectra. Experimental approaches based on dipolar correlation, chemical shift tensor analysis, and quadrupolar interaction analysis are employed to obtain detailed information about this phase. Density functional theory (DFT) calculations are used to predict chemical shielding and electric field gradient (EFG) parameters for comparison with experiment. (1)H SSNMR experiments performed at 16.4 T using magic-angle spinning (MAS) and homonuclear dipolar decoupling provide information about hydrogen bonding and molecular connectivity that can be related to the crystal structure. (19)F and (13)C assignments for the Z' = 2 structure are obtained using DFT calculations, (19)F homonuclear dipolar correlation, and (13)C-(19)F heteronuclear dipolar correlation experiments. (35)Cl MAS experiments at 16.4 T observe two chlorine sites that are assigned using calculated chemical shielding and EFG parameters. SSNMR dipolar correlation experiments are used to extract (1)H-(13)C, (1)H-(15)N, (1)H-(19)F, (13)C-(19)F, and (1)H-(35)Cl through-space connectivity information for many positions of interest. The results allow for the evaluation of the performance of a suite of SSNMR experiments and computational approaches as applied to a complex but typical pharmaceutical solid phase.