NMR Chemical Shift and Methylation of 4-Nitroimidazole: Experiment and Theory

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