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.

DNP methods can provide significant sensitivity enhancements in magic angle spinning solid-state NMR, but in systems with long polarization build up times long recycling periods are required to optimize sensitivity. We show how the sensitivity of such experiments can be improved by the classic flip-back method to recover bulk proton magnetization following continuous wave proton heteronuclear decoupling. Experiments were performed on formulations with characteristic build-up times spanning two orders of magnitude: a bulk BDPA radical doped o-terphenyl glass and microcrystalline samples of theophylline, l-histidine monohydrochloride monohydrate, and salicylic acid impregnated by incipient wetness. For these systems, addition of flip-back is simple, improves the sensitivity beyond that provided by modern heteronuclear decoupling methods such as SPINAL-64, and provides optimal sensitivity at shorter recycle delays. We show how to acquire DNP enhanced 2D refocused CP-INADEQUATE spectra with flip-back recovery, and demonstrate that the flip-back recovery method is particularly useful in rapid recycling regimes. We also report Overhauser effect DNP enhancements of over 70 at 592.6 GHz/900 MHz.

Chemical shift anisotropy (CSA) tensors offer a wealth of information for structural and dynamics studies of a variety of chemical and biological systems. In particular, CSA of amide protons can provide piercing insights into hydrogen-bonding interactions that vary with the backbone conformation of a protein and dynamics. However, the narrow span of amide proton resonances makes it very difficult to measure 1H CSAs of proteins even by using the recently proposed 2D 1H/1H anisotropic/isotropic chemical shift (CSA/CS) correlation technique. Such difficulties due to overlapping proton resonances can in general be overcome by utilizing the broad span of isotropic chemical shifts of low-gamma nuclei like 15N. In this context, we demonstrate a proton-detected 3D 15N/1H/1H CS/CSA/CS correlation experiment at fast MAS frequency (70 kHz) to measure 1H CSA values of unresolved amide protons of N-acetyl-15N-L-valyl-15N-L-leucine (NAVL).

As-prepared graphene oxide (GO) contains oxidative debris which can be washed using basic solutions. We present the isolation and characterization of these debris. Dynamic light scattering (DLS) is used to monitor the separation of the debris in various solvents in the presence of different protic and aprotic alkylamino bases. The study reveals that the debris are rich in carbonyl functional groups and water is an essential component for separation and removal of the debris from GO under oxidative reaction conditions.