The molecular conformation of Ibuprofen, C13H18O2, through X-ray diffuse scattering

A study of the three-dimensional distribution of the X-ray diffuse scattering from the pharmaceutical Ibuprofen (2-(4-isobutylphenyl)propionic acid, C(13)H(18)O(2)) has been undertaken. The most important aspects of the molecular flexibility have been isolated, as have key correlations between variables within a single molecule. Hence, aspects of the conformational space of the molecule within a crystalline environment have been outlined. For example the correlations between torsional twists on different bonds in the molecule (corresponding to the torsional angles on atoms C3, O1 and C11) have been established. Even though the atoms are on opposite sides of the phenyl group, there is a strong negative correlation between the torsional angle on C3 and that on C11. This shows that the ability to predict the conformation a fragment of a molecule will adopt based on the conformations of the fragment found in other molecules may be limited, as aspects of molecular geometry far from the fragment itself will have impact on its conformation. Between molecules, the positional coordinate components which coincide with the direction of propagation of strong intermolecular contacts, particularly the -COOH-HOOC- dimerising interactions, are positively correlated. On the other hand, motions perpendicular to such directions, and rotations about the torsional angles, do not propagate strongly from molecule to molecule.