Vadim Zorin

Chemical shift computations on a crystallographic basis: some reflections and comments.

Computations for chemical shifts of molecular organic compounds using the gauge‐including projector augmented wave method and the NMR‐CASTEP code are reviewed. The methods are briefly introduced, and some general aspects involving the sources of uncertainty in the results are explored. The limitations are outlined. Successful applications of the computations to problems of interpretation of NMR results are discussed and the range of areas in which useful information is obtained is illustrated by examples. The particular value of the computations for comparing shifts between resonances where the same chemical site is involved is emphasised. Such cases arise for shifts between different crystallographically independent molecules of the same chemical species, between polymorphs and for shift anisotropies and asymmetries. Copyright

Computation and NMR crystallography of terbutaline sulfate

This article addresses, by means of computation and advanced experiments, one of the key challenges of NMR crystallography, namely the assignment of individual resonances to specific sites in a crystal structure. Moreover, it shows how NMR can be used for crystal structure validation. The case examined is form B of terbutaline sulfate. CPMAS 13C and fast MAS 1H spectra have been recorded and the peaks assigned as far as possible. Comparison of 13C chemical shifts computed using the CASTEP program (incorporating the Gauge Including Projector Augmented Wave principle) with those obtained experimentally enable the accuracy of the two distinct single‐crystal evaluations of the structure to be compared and an error in one of these is located. The computations have substantially aided in the assignments of both 13C and 1H resonances, as has a series of two‐dimensional (2D) spectra (HETCOR, DQ‐CRAMPS and proton–proton spin diffusion). The 2D spectra have enabled many of the proton chemical shifts to be pinpointed. The relationships of the NMR shifts to the specific nuclear sites in the crystal structure have therefore been established for most 13C peaks and for some 1H signals. Emphasis is placed on the effects of hydrogen bonding on the proton chemical shifts. Copyright

Quantification of homonuclear dipolar coupling networks from magic-angle spinning 1H NMR

Numerical simulations of magic-angle spinning (MAS) spectra of dipolar-coupled nuclear spins have been used to assess different approaches to the quantification of dipolar couplings from 1H solid-state NMR. Exploiting the translational symmetry of periodic spin systems allows extended networks with ‘realistic’ numbers of spins to be considered. The experimentally accessible parameter is shown to be the root-sum-square of the dipolar couplings to a given spin. The effectiveness of either fitting the resulting spinning sideband spectra to small spin system models, or using analyses based on moment expansions, has been examined. Fitting of the spinning sideband pattern is found to be considerably more robust with respect to experimental noise than frequency domain moment analysis. The influence of the MAS rate and system geometry on robustness of the quantification is analysed and discussed.

Characterising the role of water in sildenafil citrate by NMR crystallography

A combination of solid-state NMR techniques, including 13C/1H correlation, 2H magic-angle spinning NMR and first principles calculation are employed to characterise the role of water in different hydration states of sildenafil citrate. The 13C spectrum is fully assigned for the first time and direct correlations made with respect to the crystal structure. 2H magic-angle spinning NMR is demonstrated to be a powerful tool for the study of dynamic and exchange processes in complex hydrate systems, allowing the behaviour at multiple solvate sites to be characterised without the need for expensive and selective labelling. Use of the 2H double-quantum frequency allows resolution of the different sites and, consequently, data fitting to determine rates of spin-diffusion between the different sites. The water is shown to be highly dynamic, undergoing C2 rotation, with chemical exchange between different water molecules and also with the host structure. The methods adopted are applicable to the investigation of an extensive range of hydration types found in pharmaceutical drug substances.

Heteronuclear chemical shift correlation and J-resolved MAS NMR spectroscopy of lipid membranes.

Direct observation of J‐couplings remains a challenge in high‐resolution solid‐state NMR. In some cases, it is possible to use Lee–Goldburg (LG) homonuclear decoupling during rare spin observation in MAS NMR correlation spectroscopy of lipid membranes to obtain J‐resolved spectra in the direct dimension. In one simple implementation, a wide line separation‐type 13C‐1H HETCOR can provide high‐resolution 1H/13C spectra, which are J‐resolved in both dimensions. Coupling constants, 1JHC, obtained from 1H doublets, can be compared with scaled 1JθCH‐values obtained from the 13C multiplets to assess the LG efficiency and scaling factor. The use of homonuclear decoupling during proton evolution, LG‐HETCOR‐LG, can provide J‐values, at least in the rare spin dimension, and allows measurements in less mobile membrane environments. The LG‐decoupled spectroscopic approach is demonstrated on pure dioleoylphosphatidylcholine (DOPC) membranes and used to investigate lipid mixtures of DOPC/cholesterol and DOPC/cholesterol/sphingomyelin. Copyright

A robust, general automatic phase correction algorithm for high-resolution NMR data

The trends towards rapid NMR data acquisition, automated NMR spectrum analysis, and data processing and analysis by more naïve users combine to place a higher burden on data processing software to automatically process these data. Downstream data analysis is compromised by poor processing, and the automated processing algorithms must therefore be robust and accurate. We describe a new algorithm for automatic phase correction of frequency‐domain, high‐resolution NMR spectra. We show this to be reliable for data derived from a wide variety of typical NMR usages. We therefore conclude that the method will have wide‐spread applicability and a positive impact on automated spectral processing and analysis. Copyright