COMBINATION OF CP MAS NMR AND X-RAY CRYSTALLOGRAPHY - STRUCTURE AND DYNAMICS IN A LOW-SYMMETRY MOLECULAR-CRYSTAL, POTASSIUM PENICILLIN-V

The variable-temperature C-13 CP/MAS NMR spectra of the potassium salt of phenoxymethylpenicillin (C16H17N2O5SK) (potassium penicillin V) at T < 352 K indicate an unusual low-symmetry structure with four molecules in the crystallographic asymmetric unit. This is confirmed by a single-crystal X-ray diffraction study, which employed a novel computational protocol to allow solution of the structure, which indicates that the four distinct molecules differ principally in the orientation of the phenoxy side chain with respect to the penam unit. The packing motif reveals different pseudosymmetry elements relating certain parts of the unit cell, which may explain the occurrence of this uncommon complex structure. The C-13 CP/MAS NMR spectra indicate that the phenyl rings of all the molecules perform apparently uncorrelated 180-degrees flips about their local C2 axes, at rates on the order of 10(4)-10(6) s-1 in the temperature range 180-340 K. The anisotropic thermal parameters of the X-ray structural model suggest that these rings also undergo significant librations. Between 352 and 366 K, a phase change to a structure with only two-fold asymmetry is apparent from the C-13 CP/MAS NMR spectra. Analysis of the C-13 NMR chemical shift anisotropy of the aromatic carbon atoms indicates that pairwise dynamical interchange processes between conformations similar to those present at ambient temperature account for the two-fold asymmetry of the high-temperature crystalline phase. This model enabled the disordered structure of the high-temperature phase to be refined from single-crystal X-ray diffraction data at 373 K. The anisotropic temperature factors of the aromatic rings in the ambient-temperature structure are thought to represent libration of the rings in the direction of the pairwise conformational averaging pathways of the high-temperature structure and therefore indicate restricted pretransitional dynamics. The NMR spectra suggest that the transition proceeds through a homogeneous mechanism. The combination of diffraction and NMR observations has enabled this novel conformational interchange process within a small molecule crystalline solid to be investigated in detail. The results have implications for the understanding of order/disorder transitions in molecular crystals and of conformational interchange dynamics in solids and other close-packed environments.