Conformational Polymorphism in Organic Crystals: Structural and Functional aspects - A Review

Polymorphism in organic crystals involves the formation of isomeric molecular identities. It is dependent on the structural arrangement due to inter-atomic interactions, as well as external stimuli, which include temperature, visible and UV radiation. Conformational polymorphism of organic crystalline molecules is often the result of isomerism due to the twisting and turning of angular bonds. The arrangement of the atoms supports different types of bonding mechanisms (which include hydrogen bonding) within the same compound. This, in turn, results in the formation of cis/trans configurational isomers or a proton transfer species (tautomer), having different functional properties. The conformers support the flexibility of bond angles in an attempt to reduce strains, thereby leading to the occurrence of different structural isomers resulting in polymorphism. The challenge of predicting a crystalline structure from chemical formula (connectivity of atoms in the molecule) is overcome by the recent advances in molecular mechanics simulations. The useful applications of this methodology in the field of pharmaceutical development has played a vital role in understanding the function and dynamics of the thermodynamically most stable organic crystal polymorph landscape.