19F fast MAS (60–111 kHz) dipolar and scalar based correlation spectroscopy of organic molecules and pharmaceutical formulations

Abstract

19F magic angle spinning (MAS) NMR spectroscopy is a powerful tool for characterization of fluorinated solids. The recent development of 19F MAS NMR probes, operating at spinning frequencies of 60–111 kHz, enabled analysis of systems spanning from organic molecules to pharmaceutical formulations to biological assemblies, with unprecedented resolution. Herein, we systematically evaluate the benefits of high MAS frequencies (60–111 kHz) for 1D and 2D 19F-detected experiments in two pharmaceuticals, the antimalarial drug mefloquine and a formulation of the cholesterol-lowering drug atorvastatin calcium. We demonstrate that 1H decoupling is essential and that scalar-based, heteronuclear single quantum coherence (HSQC) and heteronuclear multiple quantum coherence (HMQC) correlation experiments become feasible and efficient at the MAS frequency of 100 kHz. This study opens doors for the applications of high frequency 19F MAS NMR to a wide range of problems in chemistry and biology.