Molecular Packing in Organic Crystals: Interplay between a Molecule’s Conformation and Its Intermolecular Interactions

摘要

@@McCrone’s statement the number of polymorphs is proportional to the time and money spent in research on that compound has been frequently cited to emphasize the intriguing nature of organic crystals.1 Polymorphism was discovered as early as 1822.2 Given the ability of an organic molecule to change its conformation and exhibit the versatility of spatial packing, it appears that there could be a large number of polymorphs for any given organic molecule. Such a reception has led to both promise and concern in the pharmaceutical industry. On the one hand, a new polymorph may offer additional therapeutic properties and would definitely provide a marketing edge for extending the patent life of “blockbuster” drugs. On the other hand, failure to obtain all possible polymorphs of a new drug can considerably put pressures on the drug development because of potential risk of phase transition that can happen during manufacturing and storage (e.g., the case of ritonavir 3). All of these considerations lead to enormous efforts of polymorph screening. The recent report and debate of the second crystal structure of aspirin may highlight from a different viewpoint the great interest in the area of polymorph study.