No abstract

The salt–cocrystal continuum is a well known phenomenon in crystal engineering and has been studied here in several multicomponent solids with solid-state NMR (700 MHz) using 15N-1H heteronuclear dipolar coupling. The measurement is made at ultrafast (60–70 kHz) magic angle spinning (MAS) frequency. The experiment is sensitive enough to determine the proton position even in a continuum situation and can be performed on minimal amounts of microcrystalline or even amorphous solids with natural-abundance 15N samples. Such a measurement gives reliable values of N—H distances and is therefore a direct indication of the position of the proton in the salt–cocrystal continuum. The crystal structures of the relevant solids have also been determined at a high level of accuracy and the results of the X-ray and NMR experiments are compared.

We show how DNP enhanced solid-state NMR spectra can be dramatically simplified by suppression of solvent signals. This is achieved by (i) exploiting the paramagnetic relaxation enhancement of solvent signals relative to materials substrates, or (ii) by using short cross-polarization contact times to transfer hyperpolarization to only directly bonded carbon-13 nuclei in frozen solutions. The methods are evaluated for organic microcrystals, surfaces and frozen solutions. We show how this allows for the acquisition of high-resolution DNP enhanced proton-proton correlation experiments to measure inter-nuclear proximities in an organic solid.

Understanding the interplay between protein function and dynamics is currently one of the fundamental challenges of physical biology. Recently, a method using variable temperature solid-state nuclear magnetic resonance relaxation measurements has been proposed for the simultaneous measurement of 12 different activation energies reporting on distinct dynamic modes in the protein GB1. Here, we extend this approach to measure relaxation at multiple magnetic field strengths, allowing us to better constrain the motional models and to simultaneously evaluate the robustness and physical basis of the method. The data reveal backbone and side-chain motions, exhibiting low-and high-energy modes with temperature coefficients around 5 and 25 kJ•mol −1. The results are compared to variable temperature molecular dynamics simulation of the crystal lattice, providing further support for the interpretation of the experimental data in terms of molecular motion.

Atomically resolved crystal structures not only suffer from the inherent uncertainty in accurately locating H atoms but also are incapable of fully revealing the underlying forces enabling the formation of final structures. Therefore, the development and application of novel techniques to illuminate intermolecular forces in crystalline solids are highly relevant to understand the role of hydrogen atoms in structure adoption. Novel developments in H NMR MAS methodology can now achieve robust measurements ofH chemical shift anisotropy (CSA) tensors which are highly sensitive to electrostatics. Herein, we use H CSA tensors, measured by MAS experiments and characterized using DFT calculations, to reveal the structure-driving factors between the two polymorphic forms of acetaminophen (aka Tylenol or paracetamol) including differences in hydrogen bonding and the role of aromatic interactions. We demonstrate how theH CSAs can provide additional insights into the static picture provided by diffraction to elucidate rigid molecules.