Detailed Characterization of the Dynamics of Ibuprofen in the Solid State by a Multi-Technique NMR Approach

The internal rotations and interconformational jumps of ibu- profen in the solid state are fully characterized by the simulta- neous analysis of a variety of low- and high-resolution NMR ex- periments for the measurement of several 13C and 1H spectral and relaxation properties, performed at different temperatures and, in some cases, frequencies. The results are first qualitative- ly analyzed to identify the motions of the different molecular fragments and to assign them to specific frequency ranges (slow, < 103 Hz ; intermediate, 103–106 Hz ; and fast, > 106 Hz). In a second step, a simultaneous fit of the experimental data sets most sensitive to each frequency range is performed by means of suitable motional models to obtain, for each motion, values of correlation times and activation energies. The rotations of the three methyl groups around their ternary symmetry axes, which occur in the fast regime, are characterized by slightly different activation energies. Thanks to the simultaneous analy- sis of 1H and 13C data, the p-flip of the dimeric structure made by the acidic groups is also identified and seen to occur in the fast regime. On the contrary, the p-flip of the phenyl ring is found to occur in the slow motional regime, while the rota- tions of the isobutyl and propionic groups are frozen. The ap- proach used appears to be of general applicability for studying the dynamics of small organic molecules.