Testing the limits of NMR crystallography: the case of caffeine–citric acid hydrate

The crystal structure of a new 1:2 caffeine–citric acid hydrate cocrystal is presented. The caffeine molecules are disordered over two positions, with the nature of the disorder confirmed to be static by ¹³C solid-state NMR. NMR linewidths in statically disordered systems reflect the distribution of local chemical environments, and this study investigates whether the disorder contribution to ¹³C linewidths can be predicted computationally. The limits of NMR crystallography calculations using density functional theory are tested by investigating how geometry optimisation conditions affect calculated NMR parameters. Careful optimisation is shown to reduce differences between ¹³C constants of symmetry-related sites to about 0.1 ppm. This is just sufficient to observe a correlation between calculated and experimental linewidths, and also show that systematic errors associated with geometry optimisation do not compromise other applications of “NMR crystallography”. In addition, the unit cell enthalpies calculated after careful optimisations provide insight into why the disordered structure is adopted.