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 molecu les in the crystallographic asymmetric unit. This is confirmed by a si ngle-crystal X-ray diffraction study, which employed a novel computati onal 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 mot if reveals different pseudosymmetry elements relating certain parts of the unit cell, which may explain the occurrence of this uncommon comp lex structure. The C-13 CP/MAS NMR spectra indicate that the phenyl ri ngs of all the molecules perform apparently uncorrelated 180-degrees f lips 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 paramet ers of the X-ray structural model suggest that these rings also underg o significant librations. Between 352 and 366 K, a phase change to a s tructure 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 th e aromatic carbon atoms indicates that pairwise dynamical interchange processes between conformations similar to those present at ambient te mperature account for the two-fold asymmetry of the high-temperature c rystalline phase. This model enabled the disordered structure of the h igh-temperature phase to be refined from single-crystal X-ray diffract ion data at 373 K. The anisotropic temperature factors of the aromatic rings in the ambient-temperature structure are thought to represent l ibration of the rings in the direction of the pairwise conformational averaging pathways of the high-temperature structure and therefore ind icate restricted pretransitional dynamics. The NMR spectra suggest tha t the transition proceeds through a homogeneous mechanism. The combina tion of diffraction and NMR observations has enabled this novel confor mational interchange process within a small molecule crystalline solid to be investigated in detail. The results have implications for the u nderstanding of order/disorder transitions in molecular crystals and o f conformational interchange dynamics in solids and other close-packed environments.