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 ¹³C and ¹H isotropic chemical shifts. Gauge-including projector-augmented wave density functional theory (GIPAW DFT) calculations consistently predict a decrease in the ¹³C and ¹H magnetic shielding constants upon hydrogen bond formation on the order of 2–5 ppm (¹³C) and 1–2 ppm (¹H). These trends are reproduced using the machine-learning approach implemented in ShiftML. Experimental ¹³C and ¹H 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 ¹³C NMR response only correlates moderately well with the hydrogen bond length and angle, while the experimental ¹H chemical shifts only show very weak correlations to these local structural elements. DFT computations on isolated imidazole-formaldehyde models show that the ¹³C and ¹H chemical shifts generally decrease with the C⋯O distance but show no clear dependence on the CH⋯O angle. These results demonstrate that the ¹³C and ¹H 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。我们在这里考虑茶碱和咖啡因的一系列共晶体中的弱 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¹³ C 和¹ H 各向同性化学位移。包括投影仪的仪表增强波密度泛函理论 (GIPAW DFT) 计算一致地预测¹³ C 和¹ H 磁屏蔽常数在氢键形成时降低约 2-5 ppm ( ¹³ C) 和 1-2 ppm ( ¹小时)。使用 ShiftML 中实现的机器学习方法再现了这些趋势。实验¹³使用一维 NMR 光谱以及异核相关 (HETCOR) 光谱获得的粉末样品的C 和^{1 H 化学位移与 GIPAW DFT 结果具有很好的相关性。}然而，实验¹³ C NMR 响应仅与氢键长度和角度有适度的相关性，而实验¹ H 化学位移仅显示与这些局部结构元素的非常弱的相关性。对孤立的咪唑-甲醛模型的 DFT 计算表明，¹³ C 和¹ H 化学位移通常随着 C⋯O 距离的增加而减小，但对 CH⋯O 角没有明显的依赖性。这些结果表明¹³ C 和¹H对弱CH⋯O氢键的响应受到共晶异二聚体单元内额外的弱接触的显着影响。