Observation of H-H J-couplings in fast magic-angle-spinning solid-state NMR spectroscopy.

While H-H J-couplings are the cornerstone of all spectral assignment methods in solution-state NMR, they are yet to be observed in solids. Here we observe H-H J-couplings in plastic crystals of (1S)-(-)-camphor in solid-state NMR at magic angle spinning (MAS) rates of 100 kHz and above. This is enabled in this special case because the intrinsic coherence lifetimes at fast MAS rates become longer than the inverse of the H-H J couplings.

Crystal structure validation of verinurad proton-detected ultra-fast MAS NMR and machine learning.

The recent development of ultra-fast magic-angle spinning (MAS) (>100 kHz) provides new opportunities for structural characterization in solids. Here, we use NMR crystallography to validate the structure of verinurad, a microcrystalline active pharmaceutical ingredient. To do this, we take advantage of H resolution improvement at ultra-fast MAS and use solely H-detected experiments and machine learning methods to assign all the experimental proton and carbon chemical shifts.

Atomic-level structure of the amorphous drug atuliflapon NMR crystallography.

We determine the complete atomic-level structure of the amorphous form of the drug atuliflapon, a 5-lipooxygenase activating protein (FLAP) inhibitor, chemical-shift-driven NMR crystallography. The ensemble of preferred structures allows us to identify a number of specific conformations and interactions that stabilize the amorphous structure. These include preferred hydrogen-bonding motifs with water and with other drug molecules, as well as conformations of the cyclohexane and pyrazole rings that stabilize structure by indirectly allowing for optimization of hydrogen bonding.

Barriers to resolution in H NMR of rotating solids.

The role of H solid-state NMR in structure elucidation of solids is becoming more preponderant, particularly as faster magic-angle spinning rates (MAS) become available which improve H detected assignment strategies. However, current H spectral resolution is still relatively poor, with linewidths of typically a few hundred Hz, even at the fastest rates available today. Here we detail and assess the factors limiting proton linewidths and line shapes in MAS experiments with five different samples, exemplifying the different sources of broadening that affect the residual linewidth.

Pure Isotropic Proton NMR Spectra in Solids using Deep Learning.

The resolution of proton solid-state NMR spectra is usually limited by broadening arising from dipolar interactions between spins. Magic-angle spinning alleviates this broadening by inducing coherent averaging. However, even the highest spinning rates experimentally accessible today are not able to completely remove dipolar interactions.

Pure Isotropic Proton Solid State NMR.

Resolution in proton solid state magic angle sample spinning (MAS) NMR is limited by the intrinsically imperfect nature of coherent averaging induced by either MAS or multiple pulse sequence methods. Here, we suggest that instead of optimizing and perfecting a coherent averaging scheme, we could approach the problem by parametrically mapping the error terms due to imperfect averaging in a -space representation, in such a way that they can be removed in a multidimensional correlation leaving only the desired pure isotropic signal. We illustrate the approach here by determining pure isotropic H spectra from a series of MAS spectra acquired at different spinning rates.