Polymorphism conformationally similar molecules

A. Polymorphism Resulting from the Packing of Conformationally Similar Molecules... 

Olanzapine appears to exist in at least five polymorphic forms, and the structure of Form II has been reported [32]. Two molecules form centrosymmetric dimmers stabilized by a series of C—H - rc interactions, and the dimmers are connected by a system of intermolecular N—C—and C—H S hydrogen bonds. The structure of a monoclinic polymorph of isoxsuprine hydrochloride has been reported [33], The molecular conformation existing in the new monoclinic polymorph was found to be very similar to that existing in the known triclinic polymorph. 

The differences between the cluster skeletons of the three molecules of 2 are very small with the mean values of the Ru-Ru distances being similar and the mean Ru-C(carbide) distances being identical. The most notable differences between the structures arise from the orientation of the tricarbonyl units attached to the apical Ru atoms above and below the molecular equator of the octahedral cluster (the molecular equator is defined as the Ru4 plane in which the bridging carbonyl ligand is present). The two tricarbonyl units are almost exactly staggered in the crystal obtained from benzene, whereas they approach an eclipsed conformation in the other polymorph. Although the 13C-NMR spectrum of 2 has not been recorded in solution (or in the solid state), it is not unreasonable to anticipate that... 

The investigation of different rotational isomers of the same compound in different crystal forms polymorphs) is also an efficient tool in elucidating intermolecular interactions. The phenomenon is called conformational polymorphism. The energy differences between the polymorphs of organic crystals are similar to the free energy differences of rotational isomers of many free molecules, viz., a few kilocalories per mole. When the molecules adopt different conformations in the different polymorphs, the change in rotational isomerism is attributed to the influence of the crystal field since the difference in the intermolecular forces is the single variable in the polymorphic systems. 

Organic molecules (which of course account for most pharmaceutical agents) can exist in a variety of conformations that have similar energies. In many cases, the molecule adopts the conformation of lowest energy when it packs into a crystal. The packing-type polymorphism discussed in the previous section usually represents different modes by which molecules in their most favorable conformational state have been assembled into alternate solid structures. In some cases, however, a molecule for which different conformational states are possible yields a different polymorph when its different conformations are packed. This conformational polymorphism is therefore defined as the existence of different conformers of the same molecule in different polymorphic modifications. 

The TTP molecules are chiral because of the angle of about 55° between the planes of the tetrachlorophthalimide and p-tolyl parts of the molecule. As the space group C2 is chiral, spontaneous resolution has taken place on crystallisation but the absolute configuration of the crystal used in the structure determination could not be determined. It would be interesting to see if the chirality of the channel is adequate to resolve enantiomers but this was not attempted. The a- and y-polymorphs crystalline in centrosymmetrical space groups and thus are racemates (in a-TTP the molecules lie on crystallographic mirror planes while in y-TTP their conformation is similar to that found in the inclusion compounds). Of course the twisted TTP molecules will racemise rapidly in solution. 

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