Polymorphism salt solid-state properties

Unfortunately, our understanding of the physics and chemistry of salt formation is not yet at a stage where we can predict a priori the physicochemical properties of a proposed salt. A particular problem in this regard is the formation of a range of salt polymorphs and/or solvates. While qualitative/semiempi-rical guidelines have been developed, the selection process is still largely experiment based. It is to be hoped that developments in computational methods will soon lead to the more accurate prediction of bio-pharmaceutically relevant solid-state properties that will ultimately simplify the task of appropriate salt selection. 

Besides regulatory importance, salts, polymorphs, and hydrates/solvates have clear novelty and patentability considering their different chemical compositions or distinguishable solid state ( fon Raumer et al., 2006). Those new forms can affect not only their processibilities, such as crystallization,Lltration, and compression, but also their biological properties, such as solubility and bioavailability. Besides, the manufacturing processes for those forms are often innovative, and thus patentable. 

The isolation, identification and characterization of different crystal forms (polymorphs, solvates, salts and co-crystals) of the same molecule or of aggregates of the same molecule with other molecules represents one of the most active areas of modem solid state chenfistry. The investigation of crystal forms impacts on fundamental science as well as on utilitarian objectives because different crystal forms may display a range of different physico-chemical properties, which may affect application and utilization of the solid materials. 

Aurophilic interactions are also important in the solid-state structures of many two-coordinate gold(I) complexes. The case of [(cyclohexyl isocyanide)2Au ](PFg) presents an excellent example [33]. This salt crystallizes in two different fashions. The colorless polymorph contains strictly linear chains of cations with short contacts between the gold atoms as seen in Figure 3.8. In the yellow polymorph, [(cyclohexyl isocyanide)2Au ](PFg) crystallizes to form bent chains with even shorter separations between the gold ions. The yellow polymorph produces green emission when irradiated with a UV lamp, while under the same conditions the colorless polymorph produces blue emission. The emissive properties of these two salts are a direct consequence of the aurophilic interactions found in the chains of cations [34]. In solution, both salts fully dissociate into monomers that are colorless and nonluminescent. 

---