NMR studies of organic polymorphs & solvates

Abstract

This review article describes the applications of NMR to the study of polymorphs and related forms (solvates) of organic (especially pharmaceutical) compounds, for which it is of increasing academic and practical importance. The nature of the systems covered is briefly introduced, as are the techniques constituting solid-state NMR. The methodologies involved are then reviewed under a number of different headings, ranging from spectral editing through relaxation times to shielding tensors and NMR crystallography. In each case the relevant applications are described. Whilst most studies concentrate on structural matters, motional effects are not neglected. A special section discusses studies of solvates (especially hydrates), and another reviews quantitative analysis.

Powder crystallography of pharmaceutical materials by combined crystal structure prediction and solid-state 1H NMR spectroscopy

“…For small molecules, however, an approach based on the analysis of chemical shifts would be most attractive. There are today many examples of chemical shifts being combined with density functional theory (DFT) calculations for structure validation in organic molecular compounds with respect to known structures [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] . However, there are very few examples of ab initio structure determination from powders by NMR without a structural hypothesis.…”

NMR characterisation of dynamics in solvates and desolvates of formoterol fumarate

“…Solid-state NMR is a powerful tool for characterising structure and dynamics in molecular solids such as pharmaceuticals [6][7][8][9][10][11][12]. Figure 1 shows previously reported [13] 13 C spectra of the materials relevant to this work: (b) the CPMAS spectrum of diformoterol fumarate diethanolate, (c) and (d) the CPMAS and "direct excitation" (DE) MAS spectra respectively of form C obtained by desolvation of the ethanolate.…”

Probing Intermolecular Crystal Packing in γ-Indomethacin by High-Resolution 1H Solid-State NMR Spectroscopy

“…[16][17][18][19][20] In the context of organic molecules, a particular focus is upon the interactions that govern the adopted intermolecular packing, notably hydrogen bonding and aromatic - effects. 1 H solid-state NMR is well suited to this challenge on account of the marked sensitivity of the 1 H chemical shift to hydrogen bonding and aromatic ring current effects. [21][22][23] In particular, 1 H-1 H double-quantum spectroscopy is a powerful method for identifying proton-proton proximities up to~3.5 Å, be they intra-or intermolecular proximities.…”