Through-bonds and through-space solid-state NMR correlations at natural isotopic abundance: Signal assignment and structural study of simvastatin
Through-bonds and through-space solid-state NMR correlations at natural isotopic abundance: Signal assignment and structural study of simvastatin
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DOI：
10.1021/jp0498163
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发表时间：
2004-05-06
影响因子：
2.9
通讯作者：
Jegorov, A
中科院分区：
文献类型：
--
作者：
Brus, J;Jegorov, A
在中等大小的辛伐他汀(C25H38O5)分子上进行了天然同位素丰度(重聚焦交叉极化难以置信自然丰度双量子转移实验(CPINADEQUATE)、H-1-C-13 HETCOR、H-1-C-13魔角自旋J异核多量子相干(MAS-J-HMQC))下的穿键和穿越空间固体核磁共振关联实验。重新聚焦的C-13-C-13 CP-不具备优化的高功率去耦合性能，在获得一天内提供完整的相关频谱。通过H-1-C-13MAS-J-HMQC和偶极异核相关光谱实现了H-1和C-13信号的完全明确归属。利用偶极H-1-C-13关联和Lee-Goldburg CP(LG-CP)来促进长程极化转移。随着Lg-CP的逐渐增加，在2D光谱中检测到80多个异核接触。这些相互作用中的大多数反映了相邻结构单元之间的极化转移。大约30个交叉峰对应于所需的长程关联，其中20个可以明确地用于推导原子间距离。在2DHETCOR中，用标准的Hartrnann-Hahn共振CP作为混合周期，观察到了指示H-1-H-1极化转移的附加相干的形成。通过对X射线衍射数据的仔细分析，没有发现分子间关联和分子内关联之间存在明显的距离边界。分子间H-1-C-13接触对应于3-5埃的极化转移范围。核磁共振聚集位移表明分子间存在短程相互作用(3.0-3.3埃)。在许多情况下，相关信号必须被认为是分子间和分子内极化转移事件的贡献。2D LG-CP HETCOR的高选择性和高分辨率限制了由单个交叉峰反映的相互作用的自旋体系的大小。由于与一个碳相互作用的质子数目通常不超过3-4个，因此可以相对于异核偶极耦合来分析观察到的相关信号的偶极振荡。所获得的H-1-C-13和H-1-H-1接触结合C-13和1H核磁共振聚集位移，是在天然同位素丰度下确定晶体内有序分子的构象和相互取向的实用而有效的工具。
Through-bond and through-space solid-state NMR correlation experiments at natural isotopic abundance (refocused cross-polarization incredible natural abundance double quantum transfer experiment (CPINADEQUATE),H-1-C-13 HETCOR, H-1-C-13 magic-angle spinning J heteronuclear multiple-quantum coherence (MAS-J-HMQC)) are presented on a moderately sized molecule of simavastatin (C25H38O5). Refocused C-13-C-13 CP-INADEQUATE with an optimized performance of high-power decoupling provides full correlation spectrum within a day of acquisition. Complete unambiguous H-1 and C-13 signal assignment was achieved by H-1-C-13 MAS-J-HMQC and dipolar heteronuclear correlation spectroscopy. Dipolar H-1-C-13 correlation with Lee-Goldburg CP (LG-CP) was used to promote long-range polarization transfer. More than 80 heteronuclear contacts were detected in 2D spectra measured with gradually increasing LG-CP. The majority of these interactions reflects polarization transfer between neighboring structural units. Approximately 30 cross peaks correspond to desired long-range correlation, and 20 of them can be unambiguously used to derive interatomic distances. Formation of additional coherences indicating H-1-H-1 polarization transfer was observed applying standard Hartrnann-Hahn on-resonance CP as a mixing period in 2D HETCOR. No sharp distance border between inter- and intramolecular correlations was found by careful analysis of X-ray diffraction data. Intermolecular H-1-C-13 contacts correspond to a polarization transfer range of 3-5 Angstrom. Short-range intermolecular interactions (3.0-3.3 Angstrom) are indicated by NMR aggregation shifts. In many cases, correlation signals must be considered as a contribution of both inter- and intramolecular polarization transfer events. High selectivity and good resolution of 2D LG-CP HETCOR restricts the size of the mutually interacting spin system reflected by a single cross peak. As the number of protons interacting with one carbon does not usually exceed 3-4, the observed dipolar oscillations of correlation signals can be analyzed with respect to heteronuclear dipolar couplings. The obtained H-1-C-13 and H-1-H-1 contacts used in conjunction with C-13 and 1H NMR aggregation shifts thus appear to be a practical and efficient tool to determine conformation and mutual orientation of well-organized molecules within crystal at natural isotopic abundance.