Interplay of High-Field and Earth's Field NMR: Fluorofentanyls as a Case Study.

Earth's field NMR (EFNMR) is a useful modality for low-field NMR spectroscopy due to its availability, portability, and low cost. EFNMR can enable better line width resolution than at high fields primarily due to low magnetic susceptibility broadening. Unfortunately, EFNMR spectra are highly complex due to strong J-coupling effects and can be challenging to interpret without additional information. However, the spectral complexity paired with ultrahigh resolution offers a unique opportunity to fingerprint analytes. Herein, we show that high-field (e.g., 9.4 T) NMR and EFNMR have distinct complementary roles in explaining the NMR interactions that manifest in the respective spectra of complex molecules. Chemical shifts are nearly exclusive to high-field NMR and can enable facile observations of weak J-couplings for cursory spectral assignments, but EFNMR's ability to resolve high-precision magnitudes and signs of J-couplings is essential for fully and accurately assigning structures with high fidelity. We demonstrate this with an important category of materials, fluorinated fentanyl analogues (i.e., fluorofentanyls) and their precursors. These systems are well suited to study due to their relevance to the synthetic opioid crisis and their similarities to fluorinated pharmaceuticals and biomolecules. Results show assignment of the magnitudes and signs of J-couplings in several fluorinated precursors using both high-field and EFNMR. In select fluorofentanyls, EFNMR can provide information on J-couplings that would otherwise be inaccessible even with 3D experiments at 9.4 T. EFNMR spectra of fluorofentanyls show a strong dependence on J-coupling between 1H or 19F and 14N nuclei, where the effects that manifest in spectra may be used to gain insights into local molecular dynamics and information on 14N electric-field gradient tensors.