Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie Curie Private, Ottawa, Ontario, K1N 6N5, Canada.
Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie Curie Private, Ottawa, Ontario, K1N 6N5, Canada.
Solid State Nucl Magn Reson. 2022 Jun;119:101795. doi: 10.1016/j.ssnmr.2022.101795. Epub 2022 Apr 28.
Weak hydrogen bonds are important structure-directing elements in supramolecular chemistry and biochemistry. We consider here weak CH⋯O hydrogen bonds in a series of cocrystals of theophylline and caffeine and assess to what extent the CH⋯O distance and angle govern the observed C and H isotropic chemical shifts. Gauge-including projector-augmented wave density functional theory (GIPAW DFT) calculations consistently predict a decrease in the C and H magnetic shielding constants upon hydrogen bond formation on the order of 2-5 ppm (C) and 1-2 ppm (H). These trends are reproduced using the machine-learning approach implemented in ShiftML. Experimental C and H chemical shifts obtained for powdered samples using one-dimensional NMR spectroscopy as well as heteronuclear correlation (HETCOR) spectroscopy correlate well with the GIPAW DFT results. However, the experimental C NMR response only correlates moderately well with the hydrogen bond length and angle, while the experimental H chemical shifts only show very weak correlations to these local structural elements. DFT computations on isolated imidazole-formaldehyde models show that the C and H chemical shifts generally decrease with the C⋯O distance but show no clear dependence on the CH⋯O angle. These results demonstrate that the C and H response to weak CH⋯O hydrogen bonding is influenced significantly by additional weak contacts within cocrystal heterodimeric units.
弱氢键是超分子化学和生物化学中重要的结构导向元素。我们在此考虑茶碱和咖啡因一系列共晶中弱的 CH⋯O 氢键，并评估 CH⋯O 距离和角度在多大程度上控制观察到的 C 和 H 各向同性化学位移。包含度量的投影增强波密度泛函理论（GIPAW DFT）计算一致预测，氢键形成时 C 和 H 磁屏蔽常数会降低 2-5 ppm（C）和 1-2 ppm（H）。这些趋势可以使用 ShiftML 中实现的机器学习方法重现。使用一维 NMR 光谱和异核相关（HETCOR）光谱获得的粉末样品的实验 C 和 H 化学位移与 GIPAW DFT 结果很好地相关。然而，实验 C NMR 响应仅与氢键长度和角度中度相关，而实验 H 化学位移仅与这些局部结构元素显示出非常弱的相关性。对分离的咪唑-甲醛模型的 DFT 计算表明，C 和 H 化学位移通常随 C⋯O 距离的减小而减小，但与 CH⋯O 角度没有明显的依赖关系。这些结果表明，C 和 H 对弱 CH⋯O 氢键的响应受到共晶杂二聚体单元中额外弱相互作用的显著影响。
