Probing Intermolecular Crystal Packing in 纬-Indomethacin by High-Resolution 1H Solid-State NMR Spectroscopy

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• 作者：Jonathan P. Bradley ; Sitaram P. Velaga ; Oleg N. Antzutkin ; Steven P. Brown
• 刊名：Crystal Growth & Design
• 出版年：2011
• 出版时间：August 3, 2011
• 年：2011
• 卷：11
• 期：8
• 页码：3463-3471
• 全文大小：1017K
• 年卷期：v.11,no.8(August 3, 2011)
• ISSN：1528-7505

文摘

An NMR crystallography approach that combines experimental solid-state magic-angle-spinning (MAS) NMR with calculation is applied to the 纬 polymorph of the pharmaceutical molecule, indomethacin. First-principles calculations (GIPAW) for the full crystal structure and an isolated molecule show changes in the ¹H chemical shift for specific aliphatic and aromatic protons of over 鈭? ppm that are due to intermolecular CH-蟺 interactions. For the OH proton, ¹H double-quantum (DQ) CRAMPS (combined rotation and multiple-pulse spectroscopy) spectra reveal intermolecular H鈥揌 proximities to the OH proton of the carboxylic acid dimer as well as to specific aromatic CH protons. The enhanced resolution in ¹H DQ鈥?sup>13C spectra, recorded at 850 MHz, enables separate ¹H DQ build-up curves (as a function of the DQ recoupling time) to be extracted for the aromatic CH protons. Supported by eight-spin density-matrix simulations, it is shown how the relative maximum intensities and rates of build-up provide quantitative insight into intramolecular and intermolecular H鈥揌 proximities that characterize the crystal packing.