Conformational Polymorphism

An unambiguous definition of conformational change and conformational polymorphism, as well as a quantitative basis for the likelihood of its appearance, is reviewed. Conformational adjustment and conformational change are different phenomena. Two polymorphs are conformational polymorphs only if their conformations are related by conformational change. Conformational change requires a change of gas-phase conformer and, hence, crossing of an energy barrier. Energy differences associated with conformational variations of small organic molecules in different polymorphs are usually small. Higher-energy conformations in crystals are rare but possible for molecules that are able to break an intramolecular interaction in favor of a strong intermolecular interaction and molecules that crystallize in special symmetry positions. Polymorphic molecules containing R-bonds that are prone to both change and adjust are likely to display a rich polymorphic landscape.