Probing Hydrogen Bonding in Cocrystals and Amorphous Dispersions Using 14N–1H HMQC Solid-State NMR
datasetposted on 2016-02-19, 20:16 authored by Andrew S. Tatton, Tran N. Pham, Frederick G. Vogt, Dinu Iuga, Andrew J. Edwards, Steven P. Brown
Cocrystals and amorphous solid dispersions have generated interest in the pharmaceutical industry as an alternative to more established solid delivery forms. The identification of intermolecular hydrogen bonding interactions in a nicotinamide palmitic acid cocrystal and a 50% w/w acetaminophen–polyvinylpyrrolidone solid dispersion are reported using advanced solid-state magic-angle spinning (MAS) NMR methods. The application of a novel 14N–1H HMQC experiment, where coherence transfer is achieved via through-space couplings, is shown to identify specific hydrogen bonding motifs. Additionally, 1H isotropic chemical shifts and 14N electric field gradient (EFG) parameters, both accessible from 14N–1H HMQC experiments, are shown to be sensitive to changes in hydrogen bonding geometry. Numerous indicators of molecular association are accessible from this experiment, including NH cross-peaks occurring from intermolecular hydrogen bonds and changes in proton chemical shifts or electric field gradient parameters. First-principles calculations using the GIPAW approach that yield accurate estimates of isotropic chemical shifts, and EFG parameters were used to assist in assignment. It is envisaged that 14N–1H HMQC solid state NMR experiments could become a valuable screening technique of solid delivery forms in the pharmaceutical industry.