NMR crystallography - Three polymorphs of phenobarbital

The NMR spectra of polymorphs I, II, and III of the pharmaceutical drug compound phenobarbital are discussed in relation to the crystal structures. Whilst some features can be explained by inspection of the structures, others require more detailed work. In this paper, shielding computations for the (13)C, (15)N, and (1)H nuclei using crystallographic repetition (with optimization of the positions of all atoms) are presented. These have enabled the majority of the signals to be assigned with some confidence and several features of NMR crystallography are illuminated. In particular, resonances have been attributed separately for the three independent molecules of form I (and also for form II). Moreover, the chemically equivalent but crystallographically distinct nuclei forming the two halves of the phenyl ring (and likewise of the heteronuclear ring) have been distinguished and a structural conformational motif attached to the (15)N chemical shifts revealed. The small differences between the spectra of forms I and II (which have very closely related crystal structures) are well-reproduced. The value of computations for establishing precise assignments of signals to crystallographic sites of atoms is emphasised. Conversely, the work provides a good test of the accuracy of computations for crystalline materials.