Conformational polymorphism, definition

At first glance this definition seems straightforward. What are some of the complications For flexible molecules McCrone would include conformational polymorphs, wherein the molecule can adopt different conformations in the different crystal structures (Corradini 1973 Panagiotopoulis et al. 1974 Bernstein and Hagler 1978 Bernstein 1987). But this is a matter of degree dynamic isomerism or tautomerism... 

Conformational polymorphism is the existence of different conformers of the same molecule in different polymorphic modifications, as represented in Fig. 5.1(a),(b). Additionally, Corradini has specified fhaf fhe conformers are nearly isoenergefic, and also includes as an example, racemic and optically active crysfals for the case of chiral molecules. While both the general definition of polymorphism and chemists general understanding of conformation are fraught with nuances and special complicating circumstances, we prefer the general definition of conformational polymorphism here, without Corradini s additional qualifications. Specific questionable or unusual cases can be dealt with as encountered. 

Haleblain and McCrone (1969) have defined polymorphism as a solid crystalline phase of a given compound resulting from the possibility of at least two different arrangements of that compound in the solid state . This definition encompasses conformational polymorphism, i.e., the existence of different conformers of the same molecule in different polymorphic modifications. 

It has turned out quite difficult (or impossible) to give a satisfactory definition of polymorphy, distinguishing it from dynamic isomers (see 19) and conformational polymorphs , pseudopolymorphs , etc. For a (confusing) review of the confusion caused by the many different definitions see [Bernstein, 2002, ch. Ij. 

As many APIs carry functional groups capable of forming a myriad of intermolecular interactions let alone possess significant conformational flexibility, it is not surprising that these are prone to form polymorphs. In 1965, McCrone provided a definition for polymorphism that has prevailed, namely,... 

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