Solvent-Free Nuclear Magnetic Resonance Spectroscopy of Charged Molecules

Nuclear magnetic resonance (NMR) spectroscopy of small molecules protonated in a solvent-free environment was successfully demonstrated. The method is referred to as solvent-free protonation NMR (SoF-NMR). Leveraging matrix-assisted ionization (MAI), we generated protonated species of aniline, 4-chloroaniline, 4-aminobiphenyl, and benzocaine for NMR analysis under mild pressure and temperature conditions. The SoF-NMR spectra were compared to traditional solution NMR spectra, and the shift changes in nuclear spin resonance frequencies verify that these small molecules are protonated by 3-nitrobenzonitrile (3-NBN). As the sample pressure decreased, new spectral features appeared, indicating the presence of differently charged species. Several advantages of SoF-NMR are highlighted, such as the elimination of H/D exchange in labile protons, resulting in the precise observation of protons that are otherwise transient in solution. Notably, the data on benzocaine show evidence of neutral, N-protonated, and O-protonated species all in the same spectrum. SoF-NMR eliminates the solvent effects and interactions that can hinder important spectral features. Optimizing SoF-NMR will result in more cost-effective and efficient NMR experimentation to monitor high-temperature, solvent-free reactions. SoF-NMR has a viable future application for studying exchangeable protons, intermediates, and products in gas-phase chemistry.