Nitroimidazoles and derivatives are a class of active pharmaceutical ingredients (APIs) first introduced sixty years ago. As anti-infection agents, the structure–activity relationships of nitroimidazole compounds have been particularly difficult to study due to their low reduction potentials and unique electronic structures. In this study, we combine dynamic nuclear polarization (DNP)-enhanced solid-state (100 K), solid-state (298 K), and ¹H-¹³C heteronuclear single quantum coherence (HSQC) solution-state NMR techniques (303 K) with density functional theory (DFT) to study the ¹H, ¹³C, and ¹⁵N chemical shifts of 4-nitroimidazole (4-NI) and 1-methyl-4-nitroimidazole (CH₃-4NI). The 4-NI chemical shifts were observed at 119.4, 136.4, and 144.7 ppm for ¹³C, and at 181.5, 237.4, and 363.0 ppm for ¹⁵N. The measurements revealed that methylation (deprotonation) of the amino nitrogen N₍₁₎ of 4-NI had less effect (Δδ = −4.8 ppm) on the N₍₁₎ chemical shift but was compensated by shielding of the N₍₃₎ (Δδ = 11.6 ppm) in CH₃-4NI. The calculated chemical shifts using DFT for 4-NI and CH₃-4NI agreed well with the experimental values (within 2 %) for the imidazole carbons. However, larger discrepancies (up to 13 %) were observed between the calculated and measured ¹⁵N NMR chemical shifts for the imidazole nitrogen atoms of both molecules, which indicate that effects such as imidazole ring resonant structures and molecular dynamics may also contribute to the nitrogen chemical environment.

硝基咪唑及其衍生物是六十年前首次引入的一类活性药物成分（API）。作为抗感染剂，硝基咪唑化合物的结构-活性关系由于还原电位低和独特的电子结构而特别难以研究。在这项研究中，我们结合了动态核极化（DNP）增强的固态（100 K），固态（298 K）和¹ H- ¹³ C异核单量子相干（HSQC）溶液态NMR技术（303） K）的密度泛函理论（DFT）研究4-硝基咪唑（4-NI）和1-甲基-4-硝基咪唑（CH ₃）的¹ H，¹³ C和¹⁵ N化学位移-4NI）。在¹³ C下观察到4-NI化学位移为119.4、136.4和144.7 ppm，对于¹⁵ N在181.5、237.4和363.0 ppm处观察到。测量显示，氨基氮N _（1）的甲基化（去质子化）4-NI有效果更小（δ δ 在N = -4.8 ppm的）_（1）化学位移，但由所述N个的遮蔽补偿_（3）（δ δ 在CH = 11.6 ppm的）₃ -4NI。使用DFT计算的4-NI和CH ₃ -4NI的化学位移与咪唑碳的实验值（在2％以内）非常吻合。但是，在计算得出的值和测量值之间观察到较大的差异（最高13％）¹⁵两个分子的咪唑氮原子的N NMR化学位移，表明诸如咪唑环共振结构和分子动力学的效应也可能有助于氮化学环境。